Rheumatology

Around three-quarters of patients remained on treatment with baricitinib (Olumiant) for rheumatoid arthritis after their first 6-month assessment in an independent analysis of British Society for Rheumatology Biologics Register (BSRBR) data.

The rate of continuation was even higher, at almost 85%, in patients who had not previously been treated with a biologic or targeted synthetic disease-modifying antirheumatic drug (b/ts DMARD) before being given baricitinib. The 6-month continuation rate was also higher, at 80%, in patients who received baricitinib without additional DMARDs or steroid therapy.

Overall, the Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) score was reduced from a baseline of 5.7 to 3.4, with similar reductions seen among the subgroups of patients who had received baricitinib as monotherapy, after prior b/tsDMARDs, or no prior b/tsDMARDs.

“We’ve looked at an RA study population using data from the BSR biologics registry, to try and have a look at how patients with baricitinib are being treated and how they’re doing in this real-world setting, within the U.K.,” explained consultant rheumatologist Christopher J. Edwards, MD, of University Hospital Southampton (England) at the British Society for Rheumatology annual conference.

“Overall, effectiveness and tolerability seem to be pretty good indeed,” he said. “Sample size, of course, was small and it will be nice to see a little bit more data collected over time that allow us to be more confident in any conclusions.”

‘Getting to grips’ with baricitinib

Baricitinib is a drug that clinicians in the United Kingdom are “just getting to grips with,” observed Jon Packham, BM, DM, a consultant rheumatologist at Haywood Hospital in Stoke-on-Trent (England) who was not involved in the analysis.

“We look forward to when we’ve got a few more patients through that 6-month hurdle and we were getting even more data coming through,” Dr. Packham said.

Baricitinib was given marketing authorization in Europe for the treatment of moderate to severe RA in 2017 and so is a relatively new addition into the BSRBR-RA, which has been running for the past 20 years. It includes data on patients with RA who are newly starting a bDMARD or tsDMARD, and patients are followed up every 6 months for the first 3 years of their treatment and then annually thereafter.

Dr. Edwards presented data on some of the baseline characteristics and status of patients at the first 6-month follow-up of the BSRBR-RA. He was clear that this analysis was done independently of the BSRBR-RA study team and performed under an agreement between Eli Lilly and the BSR to allow access to the data.

Between Jan. 1, 2018, and March 31, 2019, there were 409 patients who were just starting baricitinib treatment and who were entered into the BSRBR-RA. The mean age of patients was 61 years, and the majority (76%) was female. On average, patients starting baricitinib had been diagnosed with RA for 11 years, and 62% had previously been treated with a biologic.

As per the European label, most patients were being treated with baricitinib in combination with a conventional synthetic DMARD (61%), with 40% of patients receiving it in combination with methotrexate. Around 38% of patients received baricitinib as monotherapy, and just under 30% were receiving concomitant glucocorticoids.

The majority (84%) were prescribed a 4-mg daily dose of baricitinib, with the remainder on a daily dose of 2 mg.

There were 163 patients with data available at the first 6-month follow up, and of those, 103 had prior experience of being treated with a b/ts DMARD, 59 did not, and 65 had been given baricitinib as monotherapy.
 

Reasons for discontinuation

Overall, around a quarter of patients discontinued treatment with baricitinib, and “the reasons for this were lack of efficacy in approximately a quarter and adverse events in about two-thirds of the patients,” Dr. Edwards said.

Breaking down the types of adverse events was not part of this analysis, and that information is likely to come from the BSRBR-RA study team directly.

“We have some experience in our practice in Southampton,” Dr. Edwards observed. This experience was outlined in a separate abstract at the meeting and presented by Dr. May Nwe Lwin, a clinical research fellow within Dr. Edwards’ group.

Dr. Lwin presented data on 83 patients who had received baricitinib at University Hospital Southampton between October 2017 and July 2020, 55 (65.2%) of whom remain on treatment to date, with mean follow-up of 17 months. Of the 28 patients who stopped baricitinib, 21 stopped within 12 months.

“Patients who continued on baricitinib appeared more likely to be older and female,” Dr. Lwin said.

The mean age of patients who continued on treatment after 12 months was 61.5 years but was 49 years for those who stopped earlier. The percentage of women continuing treatment at 12 months versus those stopping earlier were a respective 82% and 67%. Both findings were significant (P < .001) but “could mean nothing, or could be very interesting data to explore more,” Dr. Lwin suggested.

“However, there was no significant difference in discontinuation rates for those using mono or combination therapy, and also no effect of disease duration or seropositivity,” Dr. Lwin said.

“Most people stopped baricitinib in the first 3 months of their treatment,” Dr. Lwin reported, noting that the most common reason was a lack of efficacy in 64% of patients, with 28.5% of patients discontinuing because of side effects.

“When you look at the adverse events, the reasons for discontinuation are quite variable,” Dr. Lwin said. These included infections (one urinary tract infection, two chest infections, and a urinary tract infection), and one case each of discitis, deranged liver function, lymphoma, and personality change.

Update on the long-term safety profile

Also at the BSR annual conference, an update on the long-term safety profile of baricitinib seen in clinical trials was presented, using data from the ‘All-BARI-RA’ dataset. This includes data from nine clinical trials and one long-term extension study.

“We recently published a long-term safety analysis of this molecule involving 3,700-plus patients with exposure up to 7 years,” said Kevin L. Winthrop, MD, MPH, professor of infectious diseases and epidemiology at Oregon Health Sciences University in Portland.

Dr. Winthrop provided an update on this, adding in another 13,148 patient-years of follow-up and giving data on the safety experience with baricitinib with up to 8.4 years of exposure for some patients.

“In short, not much has changed,” Dr. Winthrop said, noting that event rates have remained stable.

The overall major adverse cardiovascular event (MACE) and overall deep vein thrombosis/pulmonary embolism event rate were both 0.5 per 100 patient-years. Referring to the latter, Dr. Winthrop called them “rock solid stable” and “it’s been that way really all the way through the development program.”

Overall, event rates per 100 patient-years for serious infections, herpes zoster, and tuberculosis were a respective 2.7, 3.0, and 0.2. Serious infection rates over time have remained similar, but “clearly age is a risk factor for infection,” Dr. Winthrop said. “I would just say it’s similar to what we see with all biologics and small molecules in this setting.”

Malignancy and death rates were also higher in older patients, but after age adjustment, these had been stable across the different analysis points.

“Malignancy overall, excluding NMSC [nonmelanoma skin cancer], the event rate is 0.9 per 100 patient-years, very similar to what we’ve seen in the prior data cuts,” he said. “The same is true for lymphoma,” he added, with an overall event rate of 0.1 per 100 patient-years.

This updated analysis, Dr. Winthrop concluded, “suggests a safety profile really very similar to what was published recently.”Dr. Edwards has received research and educational grants and advisory panel and speaker fees from Eli Lilly and from multiple other pharmaceutical companies. The analysis of BSRBR-RA data he presented was sponsored by Eli Lilly and performed independently of the BSRBR-RA study team. Dr. Packham reported no conflicts of interest; he chaired the oral abstracts sessions in which Dr. Edwards presented his findings.

Dr. Lwin did not report having any disclosures.

Dr. Winthrop has acted as a consultant to Eli Lilly and several other pharmaceutical companies and had received research or grant support from Bristol-Myers Squibb and Pfizer. The work he presented was sponsored by Eli Lilly.

Around three-quarters of patients remained on treatment with baricitinib (Olumiant) for rheumatoid arthritis after their first 6-month assessment in an independent analysis of British Society for Rheumatology Biologics Register (BSRBR) data.

The rate of continuation was even higher, at almost 85%, in patients who had not previously been treated with a biologic or targeted synthetic disease-modifying antirheumatic drug (b/ts DMARD) before being given baricitinib. The 6-month continuation rate was also higher, at 80%, in patients who received baricitinib without additional DMARDs or steroid therapy.

Overall, the Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) score was reduced from a baseline of 5.7 to 3.4, with similar reductions seen among the subgroups of patients who had received baricitinib as monotherapy, after prior b/tsDMARDs, or no prior b/tsDMARDs.

“We’ve looked at an RA study population using data from the BSR biologics registry, to try and have a look at how patients with baricitinib are being treated and how they’re doing in this real-world setting, within the U.K.,” explained consultant rheumatologist Christopher J. Edwards, MD, of University Hospital Southampton (England) at the British Society for Rheumatology annual conference.

“Overall, effectiveness and tolerability seem to be pretty good indeed,” he said. “Sample size, of course, was small and it will be nice to see a little bit more data collected over time that allow us to be more confident in any conclusions.”

‘Getting to grips’ with baricitinib

Baricitinib is a drug that clinicians in the United Kingdom are “just getting to grips with,” observed Jon Packham, BM, DM, a consultant rheumatologist at Haywood Hospital in Stoke-on-Trent (England) who was not involved in the analysis.

“We look forward to when we’ve got a few more patients through that 6-month hurdle and we were getting even more data coming through,” Dr. Packham said.

Baricitinib was given marketing authorization in Europe for the treatment of moderate to severe RA in 2017 and so is a relatively new addition into the BSRBR-RA, which has been running for the past 20 years. It includes data on patients with RA who are newly starting a bDMARD or tsDMARD, and patients are followed up every 6 months for the first 3 years of their treatment and then annually thereafter.

Dr. Edwards presented data on some of the baseline characteristics and status of patients at the first 6-month follow-up of the BSRBR-RA. He was clear that this analysis was done independently of the BSRBR-RA study team and performed under an agreement between Eli Lilly and the BSR to allow access to the data.

Between Jan. 1, 2018, and March 31, 2019, there were 409 patients who were just starting baricitinib treatment and who were entered into the BSRBR-RA. The mean age of patients was 61 years, and the majority (76%) was female. On average, patients starting baricitinib had been diagnosed with RA for 11 years, and 62% had previously been treated with a biologic.

As per the European label, most patients were being treated with baricitinib in combination with a conventional synthetic DMARD (61%), with 40% of patients receiving it in combination with methotrexate. Around 38% of patients received baricitinib as monotherapy, and just under 30% were receiving concomitant glucocorticoids.

The majority (84%) were prescribed a 4-mg daily dose of baricitinib, with the remainder on a daily dose of 2 mg.

There were 163 patients with data available at the first 6-month follow up, and of those, 103 had prior experience of being treated with a b/ts DMARD, 59 did not, and 65 had been given baricitinib as monotherapy.
 

Reasons for discontinuation

Overall, around a quarter of patients discontinued treatment with baricitinib, and “the reasons for this were lack of efficacy in approximately a quarter and adverse events in about two-thirds of the patients,” Dr. Edwards said.

Breaking down the types of adverse events was not part of this analysis, and that information is likely to come from the BSRBR-RA study team directly.

“We have some experience in our practice in Southampton,” Dr. Edwards observed. This experience was outlined in a separate abstract at the meeting and presented by Dr. May Nwe Lwin, a clinical research fellow within Dr. Edwards’ group.

Dr. Lwin presented data on 83 patients who had received baricitinib at University Hospital Southampton between October 2017 and July 2020, 55 (65.2%) of whom remain on treatment to date, with mean follow-up of 17 months. Of the 28 patients who stopped baricitinib, 21 stopped within 12 months.

“Patients who continued on baricitinib appeared more likely to be older and female,” Dr. Lwin said.

The mean age of patients who continued on treatment after 12 months was 61.5 years but was 49 years for those who stopped earlier. The percentage of women continuing treatment at 12 months versus those stopping earlier were a respective 82% and 67%. Both findings were significant (P < .001) but “could mean nothing, or could be very interesting data to explore more,” Dr. Lwin suggested.

“However, there was no significant difference in discontinuation rates for those using mono or combination therapy, and also no effect of disease duration or seropositivity,” Dr. Lwin said.

“Most people stopped baricitinib in the first 3 months of their treatment,” Dr. Lwin reported, noting that the most common reason was a lack of efficacy in 64% of patients, with 28.5% of patients discontinuing because of side effects.

“When you look at the adverse events, the reasons for discontinuation are quite variable,” Dr. Lwin said. These included infections (one urinary tract infection, two chest infections, and a urinary tract infection), and one case each of discitis, deranged liver function, lymphoma, and personality change.

Update on the long-term safety profile

Also at the BSR annual conference, an update on the long-term safety profile of baricitinib seen in clinical trials was presented, using data from the ‘All-BARI-RA’ dataset. This includes data from nine clinical trials and one long-term extension study.

“We recently published a long-term safety analysis of this molecule involving 3,700-plus patients with exposure up to 7 years,” said Kevin L. Winthrop, MD, MPH, professor of infectious diseases and epidemiology at Oregon Health Sciences University in Portland.

Dr. Winthrop provided an update on this, adding in another 13,148 patient-years of follow-up and giving data on the safety experience with baricitinib with up to 8.4 years of exposure for some patients.

“In short, not much has changed,” Dr. Winthrop said, noting that event rates have remained stable.

The overall major adverse cardiovascular event (MACE) and overall deep vein thrombosis/pulmonary embolism event rate were both 0.5 per 100 patient-years. Referring to the latter, Dr. Winthrop called them “rock solid stable” and “it’s been that way really all the way through the development program.”

Overall, event rates per 100 patient-years for serious infections, herpes zoster, and tuberculosis were a respective 2.7, 3.0, and 0.2. Serious infection rates over time have remained similar, but “clearly age is a risk factor for infection,” Dr. Winthrop said. “I would just say it’s similar to what we see with all biologics and small molecules in this setting.”

Malignancy and death rates were also higher in older patients, but after age adjustment, these had been stable across the different analysis points.

“Malignancy overall, excluding NMSC [nonmelanoma skin cancer], the event rate is 0.9 per 100 patient-years, very similar to what we’ve seen in the prior data cuts,” he said. “The same is true for lymphoma,” he added, with an overall event rate of 0.1 per 100 patient-years.

This updated analysis, Dr. Winthrop concluded, “suggests a safety profile really very similar to what was published recently.”Dr. Edwards has received research and educational grants and advisory panel and speaker fees from Eli Lilly and from multiple other pharmaceutical companies. The analysis of BSRBR-RA data he presented was sponsored by Eli Lilly and performed independently of the BSRBR-RA study team. Dr. Packham reported no conflicts of interest; he chaired the oral abstracts sessions in which Dr. Edwards presented his findings.

Dr. Lwin did not report having any disclosures.

Dr. Winthrop has acted as a consultant to Eli Lilly and several other pharmaceutical companies and had received research or grant support from Bristol-Myers Squibb and Pfizer. The work he presented was sponsored by Eli Lilly.

Around three-quarters of patients remained on treatment with baricitinib (Olumiant) for rheumatoid arthritis after their first 6-month assessment in an independent analysis of British Society for Rheumatology Biologics Register (BSRBR) data.

The rate of continuation was even higher, at almost 85%, in patients who had not previously been treated with a biologic or targeted synthetic disease-modifying antirheumatic drug (b/ts DMARD) before being given baricitinib. The 6-month continuation rate was also higher, at 80%, in patients who received baricitinib without additional DMARDs or steroid therapy.

Overall, the Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) score was reduced from a baseline of 5.7 to 3.4, with similar reductions seen among the subgroups of patients who had received baricitinib as monotherapy, after prior b/tsDMARDs, or no prior b/tsDMARDs.

“We’ve looked at an RA study population using data from the BSR biologics registry, to try and have a look at how patients with baricitinib are being treated and how they’re doing in this real-world setting, within the U.K.,” explained consultant rheumatologist Christopher J. Edwards, MD, of University Hospital Southampton (England) at the British Society for Rheumatology annual conference.

“Overall, effectiveness and tolerability seem to be pretty good indeed,” he said. “Sample size, of course, was small and it will be nice to see a little bit more data collected over time that allow us to be more confident in any conclusions.”

‘Getting to grips’ with baricitinib

Baricitinib is a drug that clinicians in the United Kingdom are “just getting to grips with,” observed Jon Packham, BM, DM, a consultant rheumatologist at Haywood Hospital in Stoke-on-Trent (England) who was not involved in the analysis.

“We look forward to when we’ve got a few more patients through that 6-month hurdle and we were getting even more data coming through,” Dr. Packham said.

Baricitinib was given marketing authorization in Europe for the treatment of moderate to severe RA in 2017 and so is a relatively new addition into the BSRBR-RA, which has been running for the past 20 years. It includes data on patients with RA who are newly starting a bDMARD or tsDMARD, and patients are followed up every 6 months for the first 3 years of their treatment and then annually thereafter.

Dr. Edwards presented data on some of the baseline characteristics and status of patients at the first 6-month follow-up of the BSRBR-RA. He was clear that this analysis was done independently of the BSRBR-RA study team and performed under an agreement between Eli Lilly and the BSR to allow access to the data.

Between Jan. 1, 2018, and March 31, 2019, there were 409 patients who were just starting baricitinib treatment and who were entered into the BSRBR-RA. The mean age of patients was 61 years, and the majority (76%) was female. On average, patients starting baricitinib had been diagnosed with RA for 11 years, and 62% had previously been treated with a biologic.

As per the European label, most patients were being treated with baricitinib in combination with a conventional synthetic DMARD (61%), with 40% of patients receiving it in combination with methotrexate. Around 38% of patients received baricitinib as monotherapy, and just under 30% were receiving concomitant glucocorticoids.

The majority (84%) were prescribed a 4-mg daily dose of baricitinib, with the remainder on a daily dose of 2 mg.

There were 163 patients with data available at the first 6-month follow up, and of those, 103 had prior experience of being treated with a b/ts DMARD, 59 did not, and 65 had been given baricitinib as monotherapy.
 

Reasons for discontinuation

Overall, around a quarter of patients discontinued treatment with baricitinib, and “the reasons for this were lack of efficacy in approximately a quarter and adverse events in about two-thirds of the patients,” Dr. Edwards said.

Breaking down the types of adverse events was not part of this analysis, and that information is likely to come from the BSRBR-RA study team directly.

“We have some experience in our practice in Southampton,” Dr. Edwards observed. This experience was outlined in a separate abstract at the meeting and presented by Dr. May Nwe Lwin, a clinical research fellow within Dr. Edwards’ group.

Dr. Lwin presented data on 83 patients who had received baricitinib at University Hospital Southampton between October 2017 and July 2020, 55 (65.2%) of whom remain on treatment to date, with mean follow-up of 17 months. Of the 28 patients who stopped baricitinib, 21 stopped within 12 months.

“Patients who continued on baricitinib appeared more likely to be older and female,” Dr. Lwin said.

The mean age of patients who continued on treatment after 12 months was 61.5 years but was 49 years for those who stopped earlier. The percentage of women continuing treatment at 12 months versus those stopping earlier were a respective 82% and 67%. Both findings were significant (P < .001) but “could mean nothing, or could be very interesting data to explore more,” Dr. Lwin suggested.

“However, there was no significant difference in discontinuation rates for those using mono or combination therapy, and also no effect of disease duration or seropositivity,” Dr. Lwin said.

“Most people stopped baricitinib in the first 3 months of their treatment,” Dr. Lwin reported, noting that the most common reason was a lack of efficacy in 64% of patients, with 28.5% of patients discontinuing because of side effects.

“When you look at the adverse events, the reasons for discontinuation are quite variable,” Dr. Lwin said. These included infections (one urinary tract infection, two chest infections, and a urinary tract infection), and one case each of discitis, deranged liver function, lymphoma, and personality change.

Update on the long-term safety profile

Also at the BSR annual conference, an update on the long-term safety profile of baricitinib seen in clinical trials was presented, using data from the ‘All-BARI-RA’ dataset. This includes data from nine clinical trials and one long-term extension study.

“We recently published a long-term safety analysis of this molecule involving 3,700-plus patients with exposure up to 7 years,” said Kevin L. Winthrop, MD, MPH, professor of infectious diseases and epidemiology at Oregon Health Sciences University in Portland.

Dr. Winthrop provided an update on this, adding in another 13,148 patient-years of follow-up and giving data on the safety experience with baricitinib with up to 8.4 years of exposure for some patients.

“In short, not much has changed,” Dr. Winthrop said, noting that event rates have remained stable.

The overall major adverse cardiovascular event (MACE) and overall deep vein thrombosis/pulmonary embolism event rate were both 0.5 per 100 patient-years. Referring to the latter, Dr. Winthrop called them “rock solid stable” and “it’s been that way really all the way through the development program.”

Overall, event rates per 100 patient-years for serious infections, herpes zoster, and tuberculosis were a respective 2.7, 3.0, and 0.2. Serious infection rates over time have remained similar, but “clearly age is a risk factor for infection,” Dr. Winthrop said. “I would just say it’s similar to what we see with all biologics and small molecules in this setting.”

Malignancy and death rates were also higher in older patients, but after age adjustment, these had been stable across the different analysis points.

“Malignancy overall, excluding NMSC [nonmelanoma skin cancer], the event rate is 0.9 per 100 patient-years, very similar to what we’ve seen in the prior data cuts,” he said. “The same is true for lymphoma,” he added, with an overall event rate of 0.1 per 100 patient-years.

This updated analysis, Dr. Winthrop concluded, “suggests a safety profile really very similar to what was published recently.”Dr. Edwards has received research and educational grants and advisory panel and speaker fees from Eli Lilly and from multiple other pharmaceutical companies. The analysis of BSRBR-RA data he presented was sponsored by Eli Lilly and performed independently of the BSRBR-RA study team. Dr. Packham reported no conflicts of interest; he chaired the oral abstracts sessions in which Dr. Edwards presented his findings.

Dr. Lwin did not report having any disclosures.

Dr. Winthrop has acted as a consultant to Eli Lilly and several other pharmaceutical companies and had received research or grant support from Bristol-Myers Squibb and Pfizer. The work he presented was sponsored by Eli Lilly.

The inadequacies and challenges of transitioning pediatric rheumatology patients to adult care were highlighted in several research studies shared at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

Steve Debenport/Getty Images

“Not surprisingly, these studies demonstrate that transition challenges remain pervasive,” Rebecca Sadun, MD, PhD, who was not involved in any of the research, said in an interview. Nevertheless, she pointed out that one of the studies showed that eight of nine sites participating in one of the studies had at least developed a formal transition policy, and three were able to fully integrate that policy into their health care system despite the ongoing pandemic.

In that study, Joyce Chang, MD, of the Children’s Hospital of Philadelphia and colleagues used structured interviews and then quantitative research to explore processes for transition polices across nine rheumatology sites. Aside from the three that had already implemented their policies, three others were preparing implementation. The other three withdrew because of COVID-19. None of the sites had reached sustainment phase. Six of the sites had access to a social work network, and two sites had fewer than four providers.

The authors found that a higher level of change efficacy or change commitment using the Organizational Readiness for Implementing Change framework did not correspond with reaching implementation.

“The first sites to reach implementation had access to [information technology] support and involved nursing, though this was not sufficient or necessary,” the authors wrote. They noted the need for strategies to reduce the burden of data collection to improve the resilience of implementation efforts against health care system stress.
 

Who more often transitions to adult care?

Effective transition policies can help reduce the likelihood of young patients falling through the cracks as they grow from adolescence into young adulthood, especially those at highest risk for losing continuity of care.

“Young adults who are both medically and socially complex are at highest risk,” said Dr. Sadun, an assistant professor of adult and pediatric rheumatology at Duke University, Durham, N.C. “This is especially true for patients with systemic illnesses, patients requiring biologic medications, and patients with custody, transportation, and financial barriers.”

Research led by Emily A. Smitherman, MD, an assistant professor of pediatric rheumatology at Children’s of Alabama in Birmingham, looked more closely at who is and is not transitioning their care. The researchers analyzed retrospective data from the CARRA Registry, including the Long-Term Follow-Up Call Registry, through December 2019. Among 1,311 patients with inactive status, 537 of these patients had juvenile idiopathic arthritis and were aged at least 18 years. Only 186 of those patients, however, had data in the Long-Term Follow-Up Registry. Patients who were Black or had lower income were less likely to have data in the Long-Term Follow-Up Registry.

Just over half the patients in the long-term registry had transferred their care to an adult rheumatologist, and 83% overall were under the care of any physician. Patients who transferred their care were significantly more likely to have private insurance (87% vs. 70%; P = .009) and were more likely to be full-time students (74% vs. 58%; P = .036).

The researchers found no association between patients’ disease status at their last CARRA Registry visit and a successful transition to adult care. However, those who had transferred care to an adult rheumatologist tended to have a higher median level of pain (4 vs. 2 on a scale of 0-10) and more disease activity (3 vs. 1 on 0-10 scale) than did those who had not transferred care (P = .022 and P = .011, respectively). A higher proportion of those who transferred care had also experienced morning stiffness over the past week (49% vs. 30%; P = .015).
 

How young adults prefer to learn transition skills

The third study aimed to better understand the experience and preferences of young adults themselves as they transitioned from pediatric to adult care. Kristine Carandang, PhD, a postdoctoral scholar at the University of California, San Diego, and colleagues first conducted focus groups with 39 adolescents and young adults, ages 16-28 years, who had rheumatic conditions. Using the qualitative data from the focus groups, they designed a survey to capture quantitative data on young patients’ experiences.

“What we’re always trying to work on is, how do we bring that youth voice more clearly into the research literature?” Courtney K. Wells, PhD, MSW, an assistant professor of social work at the University of Wisconsin–River Falls, said in an interview. She noted that both she and Dr. Carandang were patients with rheumatic diseases, so they had lived and grown up with disease themselves and then become researchers.

“We have the information that’s in the literature, but then we also both work with youth in a couple different ways, and what we hear from youth is what we heard in our paper, but it isn’t all represented in the literature,” Dr. Wells said. That disconnect is why they also included two young adults as coauthors in the study.

“As much as we appreciate the model of the six components [of health care transition], we recognize that the youth voice isn’t represented very well,” Dr. Wells said. “The way it’s written is more for doctors and policy makers and targeted for the health care system rather than the young people themselves.”

Their research bore that out. Among 137 survey respondents, aged 18-28 years, the vast majority (89%) were women and most (75%) were White. Half the patients (50%) had a diagnosis of lupus.

“For 9 out of 11 self-management and self-advocacy skills examined, there was a significant difference between how adolescent and young adult patients experienced learning self- management skills versus how they would have preferred to learn the skills,” the researchers concluded. “Overall, adolescent and young adult patients most frequently learned about transition skills from their parents. Most participants would have preferred to learn these skills from their rheumatology team.”

For example, 46.7% of the respondents learned how to communicate their medical history from their parents, but 48.5% would have preferred to learn that from their rheumatology team. Only a quarter (24.8%) had learned that skill from their health care team.

“For most of these skills, they were getting that information from their parents, which is concerning because their parents don’t necessarily have information that is accurate,” Dr. Wells said. “Their parents managed their health care, and they taught them to do it the way they were doing it.”

Just over one-third of respondents said they learned from their parents how to track their symptoms so they could answer the rheumatologists’ questions. Only one in five respondents (20.4%) had learned this skill from their rheumatology team, but 41.2% would have preferred hearing it from their health care team, compared with 22.1% who preferred learning it from their parents.

Nearly half the respondents reported learning from their parents how to advocate for themselves when dissatisfied with their care or symptoms (49.6%) and how to talk to the office staff to make appointments, fill out paperwork, and access health records (47.4%). Just over half (51.5%) would have preferred to learn about office communication from their health care team. Preferences on self-advocacy were split between learning from parents (36.8%) and learning from their health care team (31.6%).

An opportunity for other organizations to support transition

The researchers noted that education did not necessarily need to come only from rheumatologists. Other health care professionals, including nurses and social workers, could help young patients develop skills as well.

“They said they’re also open to talking to other people, but they want their rheumatologist to lead the whole process,” Dr. Wells said. While reimbursement gaps may have presented a barrier in the past, Dr. Wells said that current billing codes have removed that obstacle, allowing physicians to bill for discussing transition skills and care.

“Largely, it’s a time issue,” Dr. Wells said. “Rheumatologists are going to tell patients first about their disease, ask how their medication is working and how their health is. Then, if we have time, we’ll cover the transition pieces, and what it boils down to is that they just don’t have time.”

The respondents indicated an interest in technology that can help their education and transition, such as patient portals, telehealth, and smartphone apps.

While 66.4% of respondents said they would attend an in-person health care appointment to learn skills for transitioning to adult care, 74.5% would attend a telehealth appointment, and 77.2% would complete a structured program within a patient portal.

Dr. Wells said she doesn’t see many of the health care system pressures easing up to allow rheumatologists more time for transition care, but she sees an opportunity for organizations, such as the Arthritis Foundation or Lupus Foundation of America, to step in and help.

“It is a matter of being creative and that, ultimately, is the barrier: Whose job is it to make it happen?” she said. “That’s where some other groups are going to need to be advocates.”

Another notable set of findings from this research was the need for young patients’ access to mental health and sexual/reproductive health services. Just over two-thirds of respondents preferred to discuss these topics with their rheumatology team, but only 59.1% felt comfortable starting the conversation about mental health, and only 47.4% felt comfortable broaching the topic of reproductive/sexual health. Even more patients preferred discussing use of drugs and alcohol with their health care team (71.5%), but more patients also felt comfortable initiating that discussion (72.2%).

“It may be that somebody who’s trained to address those issues, especially the mental health piece, may be more appropriate to have that role, and that’s part of the transition, too, these other larger life issues,” Dr. Wells said. “One of the benefits of going to an adult rheumatologist is that they are the most knowledgeable and prepared to help you with those topics.”

None of the individuals quoted in this story had any disclosures to report.

The inadequacies and challenges of transitioning pediatric rheumatology patients to adult care were highlighted in several research studies shared at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

Steve Debenport/Getty Images

“Not surprisingly, these studies demonstrate that transition challenges remain pervasive,” Rebecca Sadun, MD, PhD, who was not involved in any of the research, said in an interview. Nevertheless, she pointed out that one of the studies showed that eight of nine sites participating in one of the studies had at least developed a formal transition policy, and three were able to fully integrate that policy into their health care system despite the ongoing pandemic.

In that study, Joyce Chang, MD, of the Children’s Hospital of Philadelphia and colleagues used structured interviews and then quantitative research to explore processes for transition polices across nine rheumatology sites. Aside from the three that had already implemented their policies, three others were preparing implementation. The other three withdrew because of COVID-19. None of the sites had reached sustainment phase. Six of the sites had access to a social work network, and two sites had fewer than four providers.

The authors found that a higher level of change efficacy or change commitment using the Organizational Readiness for Implementing Change framework did not correspond with reaching implementation.

“The first sites to reach implementation had access to [information technology] support and involved nursing, though this was not sufficient or necessary,” the authors wrote. They noted the need for strategies to reduce the burden of data collection to improve the resilience of implementation efforts against health care system stress.
 

Who more often transitions to adult care?

Effective transition policies can help reduce the likelihood of young patients falling through the cracks as they grow from adolescence into young adulthood, especially those at highest risk for losing continuity of care.

“Young adults who are both medically and socially complex are at highest risk,” said Dr. Sadun, an assistant professor of adult and pediatric rheumatology at Duke University, Durham, N.C. “This is especially true for patients with systemic illnesses, patients requiring biologic medications, and patients with custody, transportation, and financial barriers.”

Research led by Emily A. Smitherman, MD, an assistant professor of pediatric rheumatology at Children’s of Alabama in Birmingham, looked more closely at who is and is not transitioning their care. The researchers analyzed retrospective data from the CARRA Registry, including the Long-Term Follow-Up Call Registry, through December 2019. Among 1,311 patients with inactive status, 537 of these patients had juvenile idiopathic arthritis and were aged at least 18 years. Only 186 of those patients, however, had data in the Long-Term Follow-Up Registry. Patients who were Black or had lower income were less likely to have data in the Long-Term Follow-Up Registry.

Just over half the patients in the long-term registry had transferred their care to an adult rheumatologist, and 83% overall were under the care of any physician. Patients who transferred their care were significantly more likely to have private insurance (87% vs. 70%; P = .009) and were more likely to be full-time students (74% vs. 58%; P = .036).

The researchers found no association between patients’ disease status at their last CARRA Registry visit and a successful transition to adult care. However, those who had transferred care to an adult rheumatologist tended to have a higher median level of pain (4 vs. 2 on a scale of 0-10) and more disease activity (3 vs. 1 on 0-10 scale) than did those who had not transferred care (P = .022 and P = .011, respectively). A higher proportion of those who transferred care had also experienced morning stiffness over the past week (49% vs. 30%; P = .015).
 

How young adults prefer to learn transition skills

The third study aimed to better understand the experience and preferences of young adults themselves as they transitioned from pediatric to adult care. Kristine Carandang, PhD, a postdoctoral scholar at the University of California, San Diego, and colleagues first conducted focus groups with 39 adolescents and young adults, ages 16-28 years, who had rheumatic conditions. Using the qualitative data from the focus groups, they designed a survey to capture quantitative data on young patients’ experiences.

“What we’re always trying to work on is, how do we bring that youth voice more clearly into the research literature?” Courtney K. Wells, PhD, MSW, an assistant professor of social work at the University of Wisconsin–River Falls, said in an interview. She noted that both she and Dr. Carandang were patients with rheumatic diseases, so they had lived and grown up with disease themselves and then become researchers.

“We have the information that’s in the literature, but then we also both work with youth in a couple different ways, and what we hear from youth is what we heard in our paper, but it isn’t all represented in the literature,” Dr. Wells said. That disconnect is why they also included two young adults as coauthors in the study.

“As much as we appreciate the model of the six components [of health care transition], we recognize that the youth voice isn’t represented very well,” Dr. Wells said. “The way it’s written is more for doctors and policy makers and targeted for the health care system rather than the young people themselves.”

Their research bore that out. Among 137 survey respondents, aged 18-28 years, the vast majority (89%) were women and most (75%) were White. Half the patients (50%) had a diagnosis of lupus.

“For 9 out of 11 self-management and self-advocacy skills examined, there was a significant difference between how adolescent and young adult patients experienced learning self- management skills versus how they would have preferred to learn the skills,” the researchers concluded. “Overall, adolescent and young adult patients most frequently learned about transition skills from their parents. Most participants would have preferred to learn these skills from their rheumatology team.”

For example, 46.7% of the respondents learned how to communicate their medical history from their parents, but 48.5% would have preferred to learn that from their rheumatology team. Only a quarter (24.8%) had learned that skill from their health care team.

“For most of these skills, they were getting that information from their parents, which is concerning because their parents don’t necessarily have information that is accurate,” Dr. Wells said. “Their parents managed their health care, and they taught them to do it the way they were doing it.”

Just over one-third of respondents said they learned from their parents how to track their symptoms so they could answer the rheumatologists’ questions. Only one in five respondents (20.4%) had learned this skill from their rheumatology team, but 41.2% would have preferred hearing it from their health care team, compared with 22.1% who preferred learning it from their parents.

Nearly half the respondents reported learning from their parents how to advocate for themselves when dissatisfied with their care or symptoms (49.6%) and how to talk to the office staff to make appointments, fill out paperwork, and access health records (47.4%). Just over half (51.5%) would have preferred to learn about office communication from their health care team. Preferences on self-advocacy were split between learning from parents (36.8%) and learning from their health care team (31.6%).

An opportunity for other organizations to support transition

The researchers noted that education did not necessarily need to come only from rheumatologists. Other health care professionals, including nurses and social workers, could help young patients develop skills as well.

“They said they’re also open to talking to other people, but they want their rheumatologist to lead the whole process,” Dr. Wells said. While reimbursement gaps may have presented a barrier in the past, Dr. Wells said that current billing codes have removed that obstacle, allowing physicians to bill for discussing transition skills and care.

“Largely, it’s a time issue,” Dr. Wells said. “Rheumatologists are going to tell patients first about their disease, ask how their medication is working and how their health is. Then, if we have time, we’ll cover the transition pieces, and what it boils down to is that they just don’t have time.”

The respondents indicated an interest in technology that can help their education and transition, such as patient portals, telehealth, and smartphone apps.

While 66.4% of respondents said they would attend an in-person health care appointment to learn skills for transitioning to adult care, 74.5% would attend a telehealth appointment, and 77.2% would complete a structured program within a patient portal.

Dr. Wells said she doesn’t see many of the health care system pressures easing up to allow rheumatologists more time for transition care, but she sees an opportunity for organizations, such as the Arthritis Foundation or Lupus Foundation of America, to step in and help.

“It is a matter of being creative and that, ultimately, is the barrier: Whose job is it to make it happen?” she said. “That’s where some other groups are going to need to be advocates.”

Another notable set of findings from this research was the need for young patients’ access to mental health and sexual/reproductive health services. Just over two-thirds of respondents preferred to discuss these topics with their rheumatology team, but only 59.1% felt comfortable starting the conversation about mental health, and only 47.4% felt comfortable broaching the topic of reproductive/sexual health. Even more patients preferred discussing use of drugs and alcohol with their health care team (71.5%), but more patients also felt comfortable initiating that discussion (72.2%).

“It may be that somebody who’s trained to address those issues, especially the mental health piece, may be more appropriate to have that role, and that’s part of the transition, too, these other larger life issues,” Dr. Wells said. “One of the benefits of going to an adult rheumatologist is that they are the most knowledgeable and prepared to help you with those topics.”

None of the individuals quoted in this story had any disclosures to report.

The inadequacies and challenges of transitioning pediatric rheumatology patients to adult care were highlighted in several research studies shared at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.

Steve Debenport/Getty Images

“Not surprisingly, these studies demonstrate that transition challenges remain pervasive,” Rebecca Sadun, MD, PhD, who was not involved in any of the research, said in an interview. Nevertheless, she pointed out that one of the studies showed that eight of nine sites participating in one of the studies had at least developed a formal transition policy, and three were able to fully integrate that policy into their health care system despite the ongoing pandemic.

In that study, Joyce Chang, MD, of the Children’s Hospital of Philadelphia and colleagues used structured interviews and then quantitative research to explore processes for transition polices across nine rheumatology sites. Aside from the three that had already implemented their policies, three others were preparing implementation. The other three withdrew because of COVID-19. None of the sites had reached sustainment phase. Six of the sites had access to a social work network, and two sites had fewer than four providers.

The authors found that a higher level of change efficacy or change commitment using the Organizational Readiness for Implementing Change framework did not correspond with reaching implementation.

“The first sites to reach implementation had access to [information technology] support and involved nursing, though this was not sufficient or necessary,” the authors wrote. They noted the need for strategies to reduce the burden of data collection to improve the resilience of implementation efforts against health care system stress.
 

Who more often transitions to adult care?

Effective transition policies can help reduce the likelihood of young patients falling through the cracks as they grow from adolescence into young adulthood, especially those at highest risk for losing continuity of care.

“Young adults who are both medically and socially complex are at highest risk,” said Dr. Sadun, an assistant professor of adult and pediatric rheumatology at Duke University, Durham, N.C. “This is especially true for patients with systemic illnesses, patients requiring biologic medications, and patients with custody, transportation, and financial barriers.”

Research led by Emily A. Smitherman, MD, an assistant professor of pediatric rheumatology at Children’s of Alabama in Birmingham, looked more closely at who is and is not transitioning their care. The researchers analyzed retrospective data from the CARRA Registry, including the Long-Term Follow-Up Call Registry, through December 2019. Among 1,311 patients with inactive status, 537 of these patients had juvenile idiopathic arthritis and were aged at least 18 years. Only 186 of those patients, however, had data in the Long-Term Follow-Up Registry. Patients who were Black or had lower income were less likely to have data in the Long-Term Follow-Up Registry.

Just over half the patients in the long-term registry had transferred their care to an adult rheumatologist, and 83% overall were under the care of any physician. Patients who transferred their care were significantly more likely to have private insurance (87% vs. 70%; P = .009) and were more likely to be full-time students (74% vs. 58%; P = .036).

The researchers found no association between patients’ disease status at their last CARRA Registry visit and a successful transition to adult care. However, those who had transferred care to an adult rheumatologist tended to have a higher median level of pain (4 vs. 2 on a scale of 0-10) and more disease activity (3 vs. 1 on 0-10 scale) than did those who had not transferred care (P = .022 and P = .011, respectively). A higher proportion of those who transferred care had also experienced morning stiffness over the past week (49% vs. 30%; P = .015).
 

How young adults prefer to learn transition skills

The third study aimed to better understand the experience and preferences of young adults themselves as they transitioned from pediatric to adult care. Kristine Carandang, PhD, a postdoctoral scholar at the University of California, San Diego, and colleagues first conducted focus groups with 39 adolescents and young adults, ages 16-28 years, who had rheumatic conditions. Using the qualitative data from the focus groups, they designed a survey to capture quantitative data on young patients’ experiences.

“What we’re always trying to work on is, how do we bring that youth voice more clearly into the research literature?” Courtney K. Wells, PhD, MSW, an assistant professor of social work at the University of Wisconsin–River Falls, said in an interview. She noted that both she and Dr. Carandang were patients with rheumatic diseases, so they had lived and grown up with disease themselves and then become researchers.

“We have the information that’s in the literature, but then we also both work with youth in a couple different ways, and what we hear from youth is what we heard in our paper, but it isn’t all represented in the literature,” Dr. Wells said. That disconnect is why they also included two young adults as coauthors in the study.

“As much as we appreciate the model of the six components [of health care transition], we recognize that the youth voice isn’t represented very well,” Dr. Wells said. “The way it’s written is more for doctors and policy makers and targeted for the health care system rather than the young people themselves.”

Their research bore that out. Among 137 survey respondents, aged 18-28 years, the vast majority (89%) were women and most (75%) were White. Half the patients (50%) had a diagnosis of lupus.

“For 9 out of 11 self-management and self-advocacy skills examined, there was a significant difference between how adolescent and young adult patients experienced learning self- management skills versus how they would have preferred to learn the skills,” the researchers concluded. “Overall, adolescent and young adult patients most frequently learned about transition skills from their parents. Most participants would have preferred to learn these skills from their rheumatology team.”

For example, 46.7% of the respondents learned how to communicate their medical history from their parents, but 48.5% would have preferred to learn that from their rheumatology team. Only a quarter (24.8%) had learned that skill from their health care team.

“For most of these skills, they were getting that information from their parents, which is concerning because their parents don’t necessarily have information that is accurate,” Dr. Wells said. “Their parents managed their health care, and they taught them to do it the way they were doing it.”

Just over one-third of respondents said they learned from their parents how to track their symptoms so they could answer the rheumatologists’ questions. Only one in five respondents (20.4%) had learned this skill from their rheumatology team, but 41.2% would have preferred hearing it from their health care team, compared with 22.1% who preferred learning it from their parents.

Nearly half the respondents reported learning from their parents how to advocate for themselves when dissatisfied with their care or symptoms (49.6%) and how to talk to the office staff to make appointments, fill out paperwork, and access health records (47.4%). Just over half (51.5%) would have preferred to learn about office communication from their health care team. Preferences on self-advocacy were split between learning from parents (36.8%) and learning from their health care team (31.6%).

An opportunity for other organizations to support transition

The researchers noted that education did not necessarily need to come only from rheumatologists. Other health care professionals, including nurses and social workers, could help young patients develop skills as well.

“They said they’re also open to talking to other people, but they want their rheumatologist to lead the whole process,” Dr. Wells said. While reimbursement gaps may have presented a barrier in the past, Dr. Wells said that current billing codes have removed that obstacle, allowing physicians to bill for discussing transition skills and care.

“Largely, it’s a time issue,” Dr. Wells said. “Rheumatologists are going to tell patients first about their disease, ask how their medication is working and how their health is. Then, if we have time, we’ll cover the transition pieces, and what it boils down to is that they just don’t have time.”

The respondents indicated an interest in technology that can help their education and transition, such as patient portals, telehealth, and smartphone apps.

While 66.4% of respondents said they would attend an in-person health care appointment to learn skills for transitioning to adult care, 74.5% would attend a telehealth appointment, and 77.2% would complete a structured program within a patient portal.

Dr. Wells said she doesn’t see many of the health care system pressures easing up to allow rheumatologists more time for transition care, but she sees an opportunity for organizations, such as the Arthritis Foundation or Lupus Foundation of America, to step in and help.

“It is a matter of being creative and that, ultimately, is the barrier: Whose job is it to make it happen?” she said. “That’s where some other groups are going to need to be advocates.”

Another notable set of findings from this research was the need for young patients’ access to mental health and sexual/reproductive health services. Just over two-thirds of respondents preferred to discuss these topics with their rheumatology team, but only 59.1% felt comfortable starting the conversation about mental health, and only 47.4% felt comfortable broaching the topic of reproductive/sexual health. Even more patients preferred discussing use of drugs and alcohol with their health care team (71.5%), but more patients also felt comfortable initiating that discussion (72.2%).

“It may be that somebody who’s trained to address those issues, especially the mental health piece, may be more appropriate to have that role, and that’s part of the transition, too, these other larger life issues,” Dr. Wells said. “One of the benefits of going to an adult rheumatologist is that they are the most knowledgeable and prepared to help you with those topics.”

None of the individuals quoted in this story had any disclosures to report.

Patients with neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE) seem to benefit from rituximab (Rituxan) therapy, according to data from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR).

Indeed, the percentage of patients with active disease, as scored by the BILAG-2004 index or SLEDAI-2K (SLE Disease Activity Index 2000), fell significantly (P < .0001) when comparing pre- and postrituximab treatment scores. There was also a reduction in the dose of oral steroids used.

Interestingly, the use of concomitant cyclophosphamide might enhance the level of improvement seen in some patients, Trixy David, MBBS, reported during an abstract session at the British Society for Rheumatology annual conference.

“Larger-scale studies are warranted to establish the effectiveness of rituximab alone, or in combination with cyclophosphamide, in the treatment neuropsychiatric lupus,” said Dr. David, a clinical research fellow at the University of Manchester (England) and specialist registrar in rheumatology at the Manchester University National Health Service Foundation Trust.

Neil Basu, MBChB, PhD, who chaired the virtual session, called the findings “enlightening” and “descriptive.”

The study “provides some interesting data, which should be tested in a robust, randomized clinical trial,” he agreed, and not that clinicians should now start using rituximab for their NPSLE cases.

Dr. Basu, who is a clinical senior lecturer in rheumatology and honorary consultant rheumatologist at the Institute of Infection, Immunity and Inflammation at the University of Glasgow, added: “It is really important that we do these studies to help support a rationale for such a trial, which are obviously very expensive and require strong evidence before we go down that track. I think these data have really been quite enlightening in that respect.”

Rationale for rituximab in neuropsychiatric lupus

Managing patients with NPSLE remains an area of substantial unmet need. According to a recent review in Rheumatology, “there is a dearth of controlled clinical trials to guide management” and “therapeutic options include symptomatic, antithrombotic, and immunosuppressive agents that are supported by observational cohort studies.”

Despite being seen in at least half of all patients with SLE, neuropsychiatric disease “is not very well studied in patients with lupus, as a lot of large-scale trials tend to exclude patients with active neurological disease,” Dr. David said.

Although it is unclear why neuropsychiatric disease occurs in SLE, it could be “as a result of vascular injury or disruption of the blood brain barrier, thereby allowing the passive diffusion of autoantibodies and cytokines across through the cerebral spinal fluid, thereby generating a proinflammatory response,” Dr. David suggested.

“We know B cells are involved in the pathogenesis of lupus, and rituximab is a chimeric monoclonal antibody that selectively targets CD20-positive B cells and mediates transient B-cell depletion,” she said. Notably, there have been some small studies suggesting that rituximab may be effective in neuropsychiatric lupus, and it is currently widely used to treat refractory lupus in the United Kingdom.
 

About the BILAG-BR and results

“Our aim was to describe the baseline characteristics and short-term effectiveness of rituximab in patients treated for neuropsychiatric lupus within the BILAG-BR,” Dr. David explained.

Started in 2009, the BILAG-BR now contains information on more than 1,400 individuals with SLE who have been recruited at 62 centers in the United Kingdom. Its purpose is to evaluate the long-term safety and effectiveness of biologic drugs versus standard immunosuppressive therapy such as azathioprine, mycophenolate mofetil, cyclophosphamide, and cyclosporine. To date, 1,229 patients have been treated with biologics, of whom 1,056 have received rituximab.

A total of 74 rituximab-treated patients were identified as having active neuropsychiatric disease, making this “the largest prospective observational cohort to date, to our knowledge,” Dr. David said.

The median age of patients was 45.5 years, the majority was female (82%) and White (74%). The median disease duration was 11.5 years.

A total of 96% had multiple organ involvement and not just neuropsychiatric disease, and 91% were positive for antineutrophil antibodies.

The top six neuropsychiatric manifestations were cognitive dysfunction and lupus headache (both affecting 27.5% of patients); acute confessional state or mononeuropathy (each seen in 10% of patients); and seizure disorder and polyneuropathy, seen in a respective 8.6% and 8.7% of patients. These findings are in line with a 2011 meta-analysis, Dr. David pointed out.

BILAG-2004 scores before and after rituximab treatment were available for 50 patients. The number of patients with a BILAG A score dropped from 24 (48%) at baseline to 7 (14%) after treatment with rituximab, and the number with a BILAG B score declined from 26 (52%) at baseline to 4 (8%) after rituximab (both P < .0001).

There was also a reduction following rituximab treatment in the percentage of patients categorized as having mainly central nervous system disease (70% vs. 11%), peripheral nervous system disease (19% vs. 6%), or both (11% vs. 8%).

Total SLEDAI-2K scores were also reduced following rituximab treatment, from a median of 12 at baseline to 2 (P < .0001).

Pre- and postrituximab oral prednisolone doses were a median of 15 mg and 10 mg (P = .009).

Limitations

“Our data are from a real-world setting of patients who had active neuropsychiatric disease and were treated with rituximab,” Dr. David said. There are of course many limitations that go hand in hand with observational studies.

“There was the issue of missing data,” Dr. David said. It was difficult or not possible to determine what doses of steroids patients were taking after rituximab therapy, particularly in terms of intravenous steroids, and what doses of any other concomitant disease-modifying therapy might have been around the time that patients initiated or stopped rituximab treatment.

“These could have acted as potential confounders,” she acknowledged.

Dr. Basu noted: “My major haziness from it is the uncertainty of knowing why these patients improved. Yes, they had rituximab, but I’m sure also that they probably received high doses of steroids if they had quite severe CNS lupus which was categorized as a BILAG-A or a B.”

Patients may also be given methylprednisolone when clinicians are really concerned, he continued, and “as was quite clearly pointed out,” there was quite a lot of missing data from a steroid perspective.

Dr. David and coinvestigators reported having no conflicts of interest. The BILAG-BR is supported by funding from Lupus UK, GlaxoSmithKline, and Roche. Dr. Basu did not state having any disclosures.

Patients with neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE) seem to benefit from rituximab (Rituxan) therapy, according to data from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR).

Indeed, the percentage of patients with active disease, as scored by the BILAG-2004 index or SLEDAI-2K (SLE Disease Activity Index 2000), fell significantly (P < .0001) when comparing pre- and postrituximab treatment scores. There was also a reduction in the dose of oral steroids used.

Interestingly, the use of concomitant cyclophosphamide might enhance the level of improvement seen in some patients, Trixy David, MBBS, reported during an abstract session at the British Society for Rheumatology annual conference.

“Larger-scale studies are warranted to establish the effectiveness of rituximab alone, or in combination with cyclophosphamide, in the treatment neuropsychiatric lupus,” said Dr. David, a clinical research fellow at the University of Manchester (England) and specialist registrar in rheumatology at the Manchester University National Health Service Foundation Trust.

Neil Basu, MBChB, PhD, who chaired the virtual session, called the findings “enlightening” and “descriptive.”

The study “provides some interesting data, which should be tested in a robust, randomized clinical trial,” he agreed, and not that clinicians should now start using rituximab for their NPSLE cases.

Dr. Basu, who is a clinical senior lecturer in rheumatology and honorary consultant rheumatologist at the Institute of Infection, Immunity and Inflammation at the University of Glasgow, added: “It is really important that we do these studies to help support a rationale for such a trial, which are obviously very expensive and require strong evidence before we go down that track. I think these data have really been quite enlightening in that respect.”

Rationale for rituximab in neuropsychiatric lupus

Managing patients with NPSLE remains an area of substantial unmet need. According to a recent review in Rheumatology, “there is a dearth of controlled clinical trials to guide management” and “therapeutic options include symptomatic, antithrombotic, and immunosuppressive agents that are supported by observational cohort studies.”

Despite being seen in at least half of all patients with SLE, neuropsychiatric disease “is not very well studied in patients with lupus, as a lot of large-scale trials tend to exclude patients with active neurological disease,” Dr. David said.

Although it is unclear why neuropsychiatric disease occurs in SLE, it could be “as a result of vascular injury or disruption of the blood brain barrier, thereby allowing the passive diffusion of autoantibodies and cytokines across through the cerebral spinal fluid, thereby generating a proinflammatory response,” Dr. David suggested.

“We know B cells are involved in the pathogenesis of lupus, and rituximab is a chimeric monoclonal antibody that selectively targets CD20-positive B cells and mediates transient B-cell depletion,” she said. Notably, there have been some small studies suggesting that rituximab may be effective in neuropsychiatric lupus, and it is currently widely used to treat refractory lupus in the United Kingdom.
 

About the BILAG-BR and results

“Our aim was to describe the baseline characteristics and short-term effectiveness of rituximab in patients treated for neuropsychiatric lupus within the BILAG-BR,” Dr. David explained.

Started in 2009, the BILAG-BR now contains information on more than 1,400 individuals with SLE who have been recruited at 62 centers in the United Kingdom. Its purpose is to evaluate the long-term safety and effectiveness of biologic drugs versus standard immunosuppressive therapy such as azathioprine, mycophenolate mofetil, cyclophosphamide, and cyclosporine. To date, 1,229 patients have been treated with biologics, of whom 1,056 have received rituximab.

A total of 74 rituximab-treated patients were identified as having active neuropsychiatric disease, making this “the largest prospective observational cohort to date, to our knowledge,” Dr. David said.

The median age of patients was 45.5 years, the majority was female (82%) and White (74%). The median disease duration was 11.5 years.

A total of 96% had multiple organ involvement and not just neuropsychiatric disease, and 91% were positive for antineutrophil antibodies.

The top six neuropsychiatric manifestations were cognitive dysfunction and lupus headache (both affecting 27.5% of patients); acute confessional state or mononeuropathy (each seen in 10% of patients); and seizure disorder and polyneuropathy, seen in a respective 8.6% and 8.7% of patients. These findings are in line with a 2011 meta-analysis, Dr. David pointed out.

BILAG-2004 scores before and after rituximab treatment were available for 50 patients. The number of patients with a BILAG A score dropped from 24 (48%) at baseline to 7 (14%) after treatment with rituximab, and the number with a BILAG B score declined from 26 (52%) at baseline to 4 (8%) after rituximab (both P < .0001).

There was also a reduction following rituximab treatment in the percentage of patients categorized as having mainly central nervous system disease (70% vs. 11%), peripheral nervous system disease (19% vs. 6%), or both (11% vs. 8%).

Total SLEDAI-2K scores were also reduced following rituximab treatment, from a median of 12 at baseline to 2 (P < .0001).

Pre- and postrituximab oral prednisolone doses were a median of 15 mg and 10 mg (P = .009).

Limitations

“Our data are from a real-world setting of patients who had active neuropsychiatric disease and were treated with rituximab,” Dr. David said. There are of course many limitations that go hand in hand with observational studies.

“There was the issue of missing data,” Dr. David said. It was difficult or not possible to determine what doses of steroids patients were taking after rituximab therapy, particularly in terms of intravenous steroids, and what doses of any other concomitant disease-modifying therapy might have been around the time that patients initiated or stopped rituximab treatment.

“These could have acted as potential confounders,” she acknowledged.

Dr. Basu noted: “My major haziness from it is the uncertainty of knowing why these patients improved. Yes, they had rituximab, but I’m sure also that they probably received high doses of steroids if they had quite severe CNS lupus which was categorized as a BILAG-A or a B.”

Patients may also be given methylprednisolone when clinicians are really concerned, he continued, and “as was quite clearly pointed out,” there was quite a lot of missing data from a steroid perspective.

Dr. David and coinvestigators reported having no conflicts of interest. The BILAG-BR is supported by funding from Lupus UK, GlaxoSmithKline, and Roche. Dr. Basu did not state having any disclosures.

Patients with neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE) seem to benefit from rituximab (Rituxan) therapy, according to data from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR).

Indeed, the percentage of patients with active disease, as scored by the BILAG-2004 index or SLEDAI-2K (SLE Disease Activity Index 2000), fell significantly (P < .0001) when comparing pre- and postrituximab treatment scores. There was also a reduction in the dose of oral steroids used.

Interestingly, the use of concomitant cyclophosphamide might enhance the level of improvement seen in some patients, Trixy David, MBBS, reported during an abstract session at the British Society for Rheumatology annual conference.

“Larger-scale studies are warranted to establish the effectiveness of rituximab alone, or in combination with cyclophosphamide, in the treatment neuropsychiatric lupus,” said Dr. David, a clinical research fellow at the University of Manchester (England) and specialist registrar in rheumatology at the Manchester University National Health Service Foundation Trust.

Neil Basu, MBChB, PhD, who chaired the virtual session, called the findings “enlightening” and “descriptive.”

The study “provides some interesting data, which should be tested in a robust, randomized clinical trial,” he agreed, and not that clinicians should now start using rituximab for their NPSLE cases.

Dr. Basu, who is a clinical senior lecturer in rheumatology and honorary consultant rheumatologist at the Institute of Infection, Immunity and Inflammation at the University of Glasgow, added: “It is really important that we do these studies to help support a rationale for such a trial, which are obviously very expensive and require strong evidence before we go down that track. I think these data have really been quite enlightening in that respect.”

Rationale for rituximab in neuropsychiatric lupus

Managing patients with NPSLE remains an area of substantial unmet need. According to a recent review in Rheumatology, “there is a dearth of controlled clinical trials to guide management” and “therapeutic options include symptomatic, antithrombotic, and immunosuppressive agents that are supported by observational cohort studies.”

Despite being seen in at least half of all patients with SLE, neuropsychiatric disease “is not very well studied in patients with lupus, as a lot of large-scale trials tend to exclude patients with active neurological disease,” Dr. David said.

Although it is unclear why neuropsychiatric disease occurs in SLE, it could be “as a result of vascular injury or disruption of the blood brain barrier, thereby allowing the passive diffusion of autoantibodies and cytokines across through the cerebral spinal fluid, thereby generating a proinflammatory response,” Dr. David suggested.

“We know B cells are involved in the pathogenesis of lupus, and rituximab is a chimeric monoclonal antibody that selectively targets CD20-positive B cells and mediates transient B-cell depletion,” she said. Notably, there have been some small studies suggesting that rituximab may be effective in neuropsychiatric lupus, and it is currently widely used to treat refractory lupus in the United Kingdom.
 

About the BILAG-BR and results

“Our aim was to describe the baseline characteristics and short-term effectiveness of rituximab in patients treated for neuropsychiatric lupus within the BILAG-BR,” Dr. David explained.

Started in 2009, the BILAG-BR now contains information on more than 1,400 individuals with SLE who have been recruited at 62 centers in the United Kingdom. Its purpose is to evaluate the long-term safety and effectiveness of biologic drugs versus standard immunosuppressive therapy such as azathioprine, mycophenolate mofetil, cyclophosphamide, and cyclosporine. To date, 1,229 patients have been treated with biologics, of whom 1,056 have received rituximab.

A total of 74 rituximab-treated patients were identified as having active neuropsychiatric disease, making this “the largest prospective observational cohort to date, to our knowledge,” Dr. David said.

The median age of patients was 45.5 years, the majority was female (82%) and White (74%). The median disease duration was 11.5 years.

A total of 96% had multiple organ involvement and not just neuropsychiatric disease, and 91% were positive for antineutrophil antibodies.

The top six neuropsychiatric manifestations were cognitive dysfunction and lupus headache (both affecting 27.5% of patients); acute confessional state or mononeuropathy (each seen in 10% of patients); and seizure disorder and polyneuropathy, seen in a respective 8.6% and 8.7% of patients. These findings are in line with a 2011 meta-analysis, Dr. David pointed out.

BILAG-2004 scores before and after rituximab treatment were available for 50 patients. The number of patients with a BILAG A score dropped from 24 (48%) at baseline to 7 (14%) after treatment with rituximab, and the number with a BILAG B score declined from 26 (52%) at baseline to 4 (8%) after rituximab (both P < .0001).

There was also a reduction following rituximab treatment in the percentage of patients categorized as having mainly central nervous system disease (70% vs. 11%), peripheral nervous system disease (19% vs. 6%), or both (11% vs. 8%).

Total SLEDAI-2K scores were also reduced following rituximab treatment, from a median of 12 at baseline to 2 (P < .0001).

Pre- and postrituximab oral prednisolone doses were a median of 15 mg and 10 mg (P = .009).

Limitations

“Our data are from a real-world setting of patients who had active neuropsychiatric disease and were treated with rituximab,” Dr. David said. There are of course many limitations that go hand in hand with observational studies.

“There was the issue of missing data,” Dr. David said. It was difficult or not possible to determine what doses of steroids patients were taking after rituximab therapy, particularly in terms of intravenous steroids, and what doses of any other concomitant disease-modifying therapy might have been around the time that patients initiated or stopped rituximab treatment.

“These could have acted as potential confounders,” she acknowledged.

Dr. Basu noted: “My major haziness from it is the uncertainty of knowing why these patients improved. Yes, they had rituximab, but I’m sure also that they probably received high doses of steroids if they had quite severe CNS lupus which was categorized as a BILAG-A or a B.”

Patients may also be given methylprednisolone when clinicians are really concerned, he continued, and “as was quite clearly pointed out,” there was quite a lot of missing data from a steroid perspective.

Dr. David and coinvestigators reported having no conflicts of interest. The BILAG-BR is supported by funding from Lupus UK, GlaxoSmithKline, and Roche. Dr. Basu did not state having any disclosures.

Children with juvenile idiopathic arthritis (JIA) have nearly triple the risk of developing psoriasis after they begin therapy with tumor necrosis factor (TNF) inhibitors, according to preliminary research shared at the annual meeting of the Childhood Arthritis and Rheumatology Research Alliance (CARRA).

Previous retrospective research at the Children’s Hospital of Philadelphia had found similar results, so the goal of this study was to look at prospectively collected data from the CARRA registry that represented a broader patient population than that of a single institution, lead author Yongdong (Dan) Zhao, MD, PhD, assistant professor of rheumatology at the University of Washington, Seattle, and pediatric rheumatologist at Seattle Children’s Hospital, said in an interview.

“The take-home message is that we confirmed this finding, and everyone who prescribed this should be aware [of the risk] and also make the family aware because often the family just thinks this is eczema and they self-manage without reporting it to the physician,” Dr. Zhao said. He advised that physicians look for evidence of psoriasis at visits and, depending on the severity, be prepared with a management plan if needed.

The researchers analyzed data from patients with JIA enrolled in the CARRA registry during June 2015–January 2020. They excluded patients with a diagnosis of inflammatory bowel disease, psoriasis at or before their JIA diagnosis, or missing data regarding the timing of psoriasis diagnosis or starting TNF inhibitors.

Among 8,222 children (29% of whom were male), just over half (54%) had ever used TNF inhibitors. Most of the patients (76%) were White, and their average age at the time of JIA diagnosis was 7 years. Compared to those with no exposure to the drugs, patients who had ever been prescribed a TNF inhibitor were three times more likely to receive a diagnosis of psoriasis afterward (unadjusted hazard ratio [HR] = 3.01; P < .01). The risk dropped only slightly (HR = 2.93; P < .01) after adjustment for gender, race, family history of psoriasis, initial International League of Associations for Rheumatology classification category, and ever having taken methotrexate.

Overall median follow-up time for the cohort was 46.7 months. The overall incidence of psoriasis in the cohort was 5.28 cases per 1,000 person-years, which split into 3.24 cases for those never exposed to TNF inhibitors and 8.49 for those ever exposed. The incidence was similar (8.31 cases per 1,000 person-years) after only the first course of TNF inhibitors.

The risk appeared greatest for adalimumab, with an incidence of 12.2 cases per 1,000 person-years after a first course in TNF inhibitor-naive patients, compared to etanercept (6.31 cases) and infliximab (9.04 cases), which did not reach statistical significance. Incidence for cumulative exposure was greater for adalimumab: 13.17 cases per 1,000 person-years, compared to 5.19 cases for etanercept and 8.77 cases for infliximab.

TNF inhibitors are first-line biologic treatment for JIA and have a longer track record for safety and effectiveness than that of newer drugs, Dr. Zhao said. They’re also commonly used for children with psoriasis, said Pamela Weiss, MD, associate professor of pediatrics and epidemiology, at the University of Pennsylvania, Philadelphia, and clinical research director of rheumatology at Children’s Hospital of Philadelphia. She was not involved in the study.

“TNF inhibitors are an incredibly useful class of medications for children with arthritis, including psoriatic arthritis,” Dr. Weiss said in an interview. “I don’t think these findings impact the risk-benefit profile of TNF inhibitors as paradoxical psoriasis is a known side effect of the medication and something most of us already counsel our families and patients about before starting a TNF inhibitor medication.”

Dr. Zhao likewise did not think the findings changed these drugs’ benefit-risk profile as long as people are aware of it. If the psoriasis is mild, he said, it’s often possible to continue the TNF inhibitor therapy along with a topical medication for the psoriasis, “but if it’s really severe, or by patient preference, you may have to switch to a different TNF inhibitor or stop it,” he said. Occasionally, he has added an additional biologic to treat the psoriasis because the underlying JIA disease in the patient couldn’t be controlled without the TNF inhibitor.

Dr. Weiss similarly said that management will depend on the severity and on shared decision-making between the physician, patient, and family.

“If it’s a small area, it can often be managed with topical corticosteroids,” Dr. Weiss said. “If it involves a large area of the body or severely affects the scalp, then stopping the TNF inhibitor therapy and starting another therapy that targets a different pathway might be considered.”

The research was funded by CARRA. Dr. Zhao has received research funding from Bristol-Myers Squibb and has consulted for Novartis. Dr. Weiss has received consulting fees from Pfizer and Lilly.

Children with juvenile idiopathic arthritis (JIA) have nearly triple the risk of developing psoriasis after they begin therapy with tumor necrosis factor (TNF) inhibitors, according to preliminary research shared at the annual meeting of the Childhood Arthritis and Rheumatology Research Alliance (CARRA).

Previous retrospective research at the Children’s Hospital of Philadelphia had found similar results, so the goal of this study was to look at prospectively collected data from the CARRA registry that represented a broader patient population than that of a single institution, lead author Yongdong (Dan) Zhao, MD, PhD, assistant professor of rheumatology at the University of Washington, Seattle, and pediatric rheumatologist at Seattle Children’s Hospital, said in an interview.

“The take-home message is that we confirmed this finding, and everyone who prescribed this should be aware [of the risk] and also make the family aware because often the family just thinks this is eczema and they self-manage without reporting it to the physician,” Dr. Zhao said. He advised that physicians look for evidence of psoriasis at visits and, depending on the severity, be prepared with a management plan if needed.

The researchers analyzed data from patients with JIA enrolled in the CARRA registry during June 2015–January 2020. They excluded patients with a diagnosis of inflammatory bowel disease, psoriasis at or before their JIA diagnosis, or missing data regarding the timing of psoriasis diagnosis or starting TNF inhibitors.

Among 8,222 children (29% of whom were male), just over half (54%) had ever used TNF inhibitors. Most of the patients (76%) were White, and their average age at the time of JIA diagnosis was 7 years. Compared to those with no exposure to the drugs, patients who had ever been prescribed a TNF inhibitor were three times more likely to receive a diagnosis of psoriasis afterward (unadjusted hazard ratio [HR] = 3.01; P < .01). The risk dropped only slightly (HR = 2.93; P < .01) after adjustment for gender, race, family history of psoriasis, initial International League of Associations for Rheumatology classification category, and ever having taken methotrexate.

Overall median follow-up time for the cohort was 46.7 months. The overall incidence of psoriasis in the cohort was 5.28 cases per 1,000 person-years, which split into 3.24 cases for those never exposed to TNF inhibitors and 8.49 for those ever exposed. The incidence was similar (8.31 cases per 1,000 person-years) after only the first course of TNF inhibitors.

The risk appeared greatest for adalimumab, with an incidence of 12.2 cases per 1,000 person-years after a first course in TNF inhibitor-naive patients, compared to etanercept (6.31 cases) and infliximab (9.04 cases), which did not reach statistical significance. Incidence for cumulative exposure was greater for adalimumab: 13.17 cases per 1,000 person-years, compared to 5.19 cases for etanercept and 8.77 cases for infliximab.

TNF inhibitors are first-line biologic treatment for JIA and have a longer track record for safety and effectiveness than that of newer drugs, Dr. Zhao said. They’re also commonly used for children with psoriasis, said Pamela Weiss, MD, associate professor of pediatrics and epidemiology, at the University of Pennsylvania, Philadelphia, and clinical research director of rheumatology at Children’s Hospital of Philadelphia. She was not involved in the study.

“TNF inhibitors are an incredibly useful class of medications for children with arthritis, including psoriatic arthritis,” Dr. Weiss said in an interview. “I don’t think these findings impact the risk-benefit profile of TNF inhibitors as paradoxical psoriasis is a known side effect of the medication and something most of us already counsel our families and patients about before starting a TNF inhibitor medication.”

Dr. Zhao likewise did not think the findings changed these drugs’ benefit-risk profile as long as people are aware of it. If the psoriasis is mild, he said, it’s often possible to continue the TNF inhibitor therapy along with a topical medication for the psoriasis, “but if it’s really severe, or by patient preference, you may have to switch to a different TNF inhibitor or stop it,” he said. Occasionally, he has added an additional biologic to treat the psoriasis because the underlying JIA disease in the patient couldn’t be controlled without the TNF inhibitor.

Dr. Weiss similarly said that management will depend on the severity and on shared decision-making between the physician, patient, and family.

“If it’s a small area, it can often be managed with topical corticosteroids,” Dr. Weiss said. “If it involves a large area of the body or severely affects the scalp, then stopping the TNF inhibitor therapy and starting another therapy that targets a different pathway might be considered.”

The research was funded by CARRA. Dr. Zhao has received research funding from Bristol-Myers Squibb and has consulted for Novartis. Dr. Weiss has received consulting fees from Pfizer and Lilly.

Children with juvenile idiopathic arthritis (JIA) have nearly triple the risk of developing psoriasis after they begin therapy with tumor necrosis factor (TNF) inhibitors, according to preliminary research shared at the annual meeting of the Childhood Arthritis and Rheumatology Research Alliance (CARRA).

Previous retrospective research at the Children’s Hospital of Philadelphia had found similar results, so the goal of this study was to look at prospectively collected data from the CARRA registry that represented a broader patient population than that of a single institution, lead author Yongdong (Dan) Zhao, MD, PhD, assistant professor of rheumatology at the University of Washington, Seattle, and pediatric rheumatologist at Seattle Children’s Hospital, said in an interview.

“The take-home message is that we confirmed this finding, and everyone who prescribed this should be aware [of the risk] and also make the family aware because often the family just thinks this is eczema and they self-manage without reporting it to the physician,” Dr. Zhao said. He advised that physicians look for evidence of psoriasis at visits and, depending on the severity, be prepared with a management plan if needed.

The researchers analyzed data from patients with JIA enrolled in the CARRA registry during June 2015–January 2020. They excluded patients with a diagnosis of inflammatory bowel disease, psoriasis at or before their JIA diagnosis, or missing data regarding the timing of psoriasis diagnosis or starting TNF inhibitors.

Among 8,222 children (29% of whom were male), just over half (54%) had ever used TNF inhibitors. Most of the patients (76%) were White, and their average age at the time of JIA diagnosis was 7 years. Compared to those with no exposure to the drugs, patients who had ever been prescribed a TNF inhibitor were three times more likely to receive a diagnosis of psoriasis afterward (unadjusted hazard ratio [HR] = 3.01; P < .01). The risk dropped only slightly (HR = 2.93; P < .01) after adjustment for gender, race, family history of psoriasis, initial International League of Associations for Rheumatology classification category, and ever having taken methotrexate.

Overall median follow-up time for the cohort was 46.7 months. The overall incidence of psoriasis in the cohort was 5.28 cases per 1,000 person-years, which split into 3.24 cases for those never exposed to TNF inhibitors and 8.49 for those ever exposed. The incidence was similar (8.31 cases per 1,000 person-years) after only the first course of TNF inhibitors.

The risk appeared greatest for adalimumab, with an incidence of 12.2 cases per 1,000 person-years after a first course in TNF inhibitor-naive patients, compared to etanercept (6.31 cases) and infliximab (9.04 cases), which did not reach statistical significance. Incidence for cumulative exposure was greater for adalimumab: 13.17 cases per 1,000 person-years, compared to 5.19 cases for etanercept and 8.77 cases for infliximab.

TNF inhibitors are first-line biologic treatment for JIA and have a longer track record for safety and effectiveness than that of newer drugs, Dr. Zhao said. They’re also commonly used for children with psoriasis, said Pamela Weiss, MD, associate professor of pediatrics and epidemiology, at the University of Pennsylvania, Philadelphia, and clinical research director of rheumatology at Children’s Hospital of Philadelphia. She was not involved in the study.

“TNF inhibitors are an incredibly useful class of medications for children with arthritis, including psoriatic arthritis,” Dr. Weiss said in an interview. “I don’t think these findings impact the risk-benefit profile of TNF inhibitors as paradoxical psoriasis is a known side effect of the medication and something most of us already counsel our families and patients about before starting a TNF inhibitor medication.”

Dr. Zhao likewise did not think the findings changed these drugs’ benefit-risk profile as long as people are aware of it. If the psoriasis is mild, he said, it’s often possible to continue the TNF inhibitor therapy along with a topical medication for the psoriasis, “but if it’s really severe, or by patient preference, you may have to switch to a different TNF inhibitor or stop it,” he said. Occasionally, he has added an additional biologic to treat the psoriasis because the underlying JIA disease in the patient couldn’t be controlled without the TNF inhibitor.

Dr. Weiss similarly said that management will depend on the severity and on shared decision-making between the physician, patient, and family.

“If it’s a small area, it can often be managed with topical corticosteroids,” Dr. Weiss said. “If it involves a large area of the body or severely affects the scalp, then stopping the TNF inhibitor therapy and starting another therapy that targets a different pathway might be considered.”

The research was funded by CARRA. Dr. Zhao has received research funding from Bristol-Myers Squibb and has consulted for Novartis. Dr. Weiss has received consulting fees from Pfizer and Lilly.

The order in which tocilizumab (Actemra) is used in the sequence of treatments for rheumatoid arthritis could be muddying the waters when it comes to evaluating patients’ risk for serious infection.

According to new data emerging from the British Society for Rheumatology Biologics Register – Rheumatoid Arthritis (BSRBR-RA), the line of therapy is a confounding factor when examining the risk for serious infection with not only tocilizumab but also other biologic agents.

The good news for patients, however, is that there doesn’t appear to be any overall greater risk for serious infection with one biologic over another when the line of therapy is taken into account.

“We don’t have any strong signal that there is an increased risk of serious infections with tocilizumab, compared to TNF inhibitors,” rheumatologist Kim Lauper, MD, of Geneva University Hospitals, said in an interview after presenting the data at the annual conference of the British Society for Rheumatology.

This is in contrast to studies where an increased risk of infections with tocilizumab has been seen when compared to TNF inhibitors. However, those studies did not account for the line of therapy, explained Dr. Lauper, who is also a clinical research fellow in the Centre for Epidemiology Versus Arthritis at the University of Manchester (England), where the BSRBR-RA is managed.

“Tocilizumab is a treatment that we often give to patients after several other treatments, so they’re really different patients,” Dr. Lauper observed. Indeed, in the “real-world” setting, patients taking tocilizumab tend to be older, have longer disease duration, and have worse functional status than do those who might receive other biologics.

To look at the effect of line of therapy on the serious infection risk associated with commonly used biologic drugs, Dr. Lauper and associates examined data on more than 33,000 treatment courses, representing more than 62,500 patient-years.

Using etanercept as the comparator – because it represents the largest group of patients in the BSRBR-RA – the serious infection risk for tocilizumab, rituximab, adalimumab, infliximab, certolizumab pegol, and abatacept were calculated as an overall rate, and for their use as first-, second-, third-, fourth-, or fifth-line therapy.

The researchers adjusted their analysis for some clear baseline differences between the treatment groups, including age, prior treatment, disease duration, and comorbidities. Seropositivity, smoking status, general health status, and disease activity scores were also adjusted for in the analysis.

Crude hazard ratios (HRs), compared with etanercept, before and after adjusting for these already-known confounding factors were 1.0 and 1.2 for tocilizumab, 1.1 and 1.1 for adalimumab, 1.4 and 1.3 for infliximab, 0.6 and 0.8 for certolizumab pegol, 0.9 and 1.0 for rituximab, and 0.9 and 1.2 for abatacept.

Stratifying by line of therapy, however, changed the results: HRs were no longer significantly different, compared with etanercept, for tocilizumab, adalimumab, and infliximab for most lines of therapy.

Indeed, while the risk for serious infection occurring with tocilizumab was 20% higher overall, compared with etanercept, that risk was actually lower if tocilizumab had been used as first- or fifth-line therapy (HRs for both, 0.9) but higher if it had been used as a third- or fourth-line therapy (HR of 1.4 for both).

“We often use tocilizumab as a second-line, third-line, or even fourth-line therapy, and if we don’t adjust for anything, we can have the impression that there are more infections with tocilizumab. But then, when we adjust for confounding factors and the line of therapy, we don’t have this anymore,” Dr. Lauper said.

“Line of therapy in itself is not a risk for serious infections,” she said in qualifying the conclusions that could be drawn from the study. “It may be a marker of the disease or some patient characteristic that is associated with a higher risk of infections.” Nevertheless, it should be taken into account when evaluating serious outcomes and possibly other safety and effectiveness outcomes.

“I understand concentrating on the hospitalized infections because the data are so much more robust,” observed consultant rheumatologist Jon Packham, BM, DM, of Haywood Hospital in Stoke-on-Trent, England, who chaired the session. He queried if there were any data on milder or just antibiotic-treated infections. At present, there aren’t those data to look at, Dr. Lauper responded, as this is something that’s difficult for registers to capture because doctors often do not log them in the databases.

There are also too few data on Janus kinase (JAK) inhibitors currently in the BSRBR-RA at present to be able to look at their rate of serious infection by line of therapy, Dr. Lauper noted. Because JAK inhibitors act on cytokines different from those affected by biologics for RA, there may be a difference there, but more data are needed on the JAK inhibitors before that question can be analyzed.

Dr. Lauper did not state having any disclosures. The BSRBR-RA is funded by the BSR via restricted income grants from several U.K. pharmaceutical companies, which has included or currently includes AbbVie, Celltrion, Hospira, Pfizer, UCB, Roche, Swedish Orphan Biovitrum, and Merck.

The order in which tocilizumab (Actemra) is used in the sequence of treatments for rheumatoid arthritis could be muddying the waters when it comes to evaluating patients’ risk for serious infection.

According to new data emerging from the British Society for Rheumatology Biologics Register – Rheumatoid Arthritis (BSRBR-RA), the line of therapy is a confounding factor when examining the risk for serious infection with not only tocilizumab but also other biologic agents.

The good news for patients, however, is that there doesn’t appear to be any overall greater risk for serious infection with one biologic over another when the line of therapy is taken into account.

“We don’t have any strong signal that there is an increased risk of serious infections with tocilizumab, compared to TNF inhibitors,” rheumatologist Kim Lauper, MD, of Geneva University Hospitals, said in an interview after presenting the data at the annual conference of the British Society for Rheumatology.

This is in contrast to studies where an increased risk of infections with tocilizumab has been seen when compared to TNF inhibitors. However, those studies did not account for the line of therapy, explained Dr. Lauper, who is also a clinical research fellow in the Centre for Epidemiology Versus Arthritis at the University of Manchester (England), where the BSRBR-RA is managed.

“Tocilizumab is a treatment that we often give to patients after several other treatments, so they’re really different patients,” Dr. Lauper observed. Indeed, in the “real-world” setting, patients taking tocilizumab tend to be older, have longer disease duration, and have worse functional status than do those who might receive other biologics.

To look at the effect of line of therapy on the serious infection risk associated with commonly used biologic drugs, Dr. Lauper and associates examined data on more than 33,000 treatment courses, representing more than 62,500 patient-years.

Using etanercept as the comparator – because it represents the largest group of patients in the BSRBR-RA – the serious infection risk for tocilizumab, rituximab, adalimumab, infliximab, certolizumab pegol, and abatacept were calculated as an overall rate, and for their use as first-, second-, third-, fourth-, or fifth-line therapy.

The researchers adjusted their analysis for some clear baseline differences between the treatment groups, including age, prior treatment, disease duration, and comorbidities. Seropositivity, smoking status, general health status, and disease activity scores were also adjusted for in the analysis.

Crude hazard ratios (HRs), compared with etanercept, before and after adjusting for these already-known confounding factors were 1.0 and 1.2 for tocilizumab, 1.1 and 1.1 for adalimumab, 1.4 and 1.3 for infliximab, 0.6 and 0.8 for certolizumab pegol, 0.9 and 1.0 for rituximab, and 0.9 and 1.2 for abatacept.

Stratifying by line of therapy, however, changed the results: HRs were no longer significantly different, compared with etanercept, for tocilizumab, adalimumab, and infliximab for most lines of therapy.

Indeed, while the risk for serious infection occurring with tocilizumab was 20% higher overall, compared with etanercept, that risk was actually lower if tocilizumab had been used as first- or fifth-line therapy (HRs for both, 0.9) but higher if it had been used as a third- or fourth-line therapy (HR of 1.4 for both).

“We often use tocilizumab as a second-line, third-line, or even fourth-line therapy, and if we don’t adjust for anything, we can have the impression that there are more infections with tocilizumab. But then, when we adjust for confounding factors and the line of therapy, we don’t have this anymore,” Dr. Lauper said.

“Line of therapy in itself is not a risk for serious infections,” she said in qualifying the conclusions that could be drawn from the study. “It may be a marker of the disease or some patient characteristic that is associated with a higher risk of infections.” Nevertheless, it should be taken into account when evaluating serious outcomes and possibly other safety and effectiveness outcomes.

“I understand concentrating on the hospitalized infections because the data are so much more robust,” observed consultant rheumatologist Jon Packham, BM, DM, of Haywood Hospital in Stoke-on-Trent, England, who chaired the session. He queried if there were any data on milder or just antibiotic-treated infections. At present, there aren’t those data to look at, Dr. Lauper responded, as this is something that’s difficult for registers to capture because doctors often do not log them in the databases.

There are also too few data on Janus kinase (JAK) inhibitors currently in the BSRBR-RA at present to be able to look at their rate of serious infection by line of therapy, Dr. Lauper noted. Because JAK inhibitors act on cytokines different from those affected by biologics for RA, there may be a difference there, but more data are needed on the JAK inhibitors before that question can be analyzed.

Dr. Lauper did not state having any disclosures. The BSRBR-RA is funded by the BSR via restricted income grants from several U.K. pharmaceutical companies, which has included or currently includes AbbVie, Celltrion, Hospira, Pfizer, UCB, Roche, Swedish Orphan Biovitrum, and Merck.

The order in which tocilizumab (Actemra) is used in the sequence of treatments for rheumatoid arthritis could be muddying the waters when it comes to evaluating patients’ risk for serious infection.

According to new data emerging from the British Society for Rheumatology Biologics Register – Rheumatoid Arthritis (BSRBR-RA), the line of therapy is a confounding factor when examining the risk for serious infection with not only tocilizumab but also other biologic agents.

The good news for patients, however, is that there doesn’t appear to be any overall greater risk for serious infection with one biologic over another when the line of therapy is taken into account.

“We don’t have any strong signal that there is an increased risk of serious infections with tocilizumab, compared to TNF inhibitors,” rheumatologist Kim Lauper, MD, of Geneva University Hospitals, said in an interview after presenting the data at the annual conference of the British Society for Rheumatology.

This is in contrast to studies where an increased risk of infections with tocilizumab has been seen when compared to TNF inhibitors. However, those studies did not account for the line of therapy, explained Dr. Lauper, who is also a clinical research fellow in the Centre for Epidemiology Versus Arthritis at the University of Manchester (England), where the BSRBR-RA is managed.

“Tocilizumab is a treatment that we often give to patients after several other treatments, so they’re really different patients,” Dr. Lauper observed. Indeed, in the “real-world” setting, patients taking tocilizumab tend to be older, have longer disease duration, and have worse functional status than do those who might receive other biologics.

To look at the effect of line of therapy on the serious infection risk associated with commonly used biologic drugs, Dr. Lauper and associates examined data on more than 33,000 treatment courses, representing more than 62,500 patient-years.

Using etanercept as the comparator – because it represents the largest group of patients in the BSRBR-RA – the serious infection risk for tocilizumab, rituximab, adalimumab, infliximab, certolizumab pegol, and abatacept were calculated as an overall rate, and for their use as first-, second-, third-, fourth-, or fifth-line therapy.

The researchers adjusted their analysis for some clear baseline differences between the treatment groups, including age, prior treatment, disease duration, and comorbidities. Seropositivity, smoking status, general health status, and disease activity scores were also adjusted for in the analysis.

Crude hazard ratios (HRs), compared with etanercept, before and after adjusting for these already-known confounding factors were 1.0 and 1.2 for tocilizumab, 1.1 and 1.1 for adalimumab, 1.4 and 1.3 for infliximab, 0.6 and 0.8 for certolizumab pegol, 0.9 and 1.0 for rituximab, and 0.9 and 1.2 for abatacept.

Stratifying by line of therapy, however, changed the results: HRs were no longer significantly different, compared with etanercept, for tocilizumab, adalimumab, and infliximab for most lines of therapy.

Indeed, while the risk for serious infection occurring with tocilizumab was 20% higher overall, compared with etanercept, that risk was actually lower if tocilizumab had been used as first- or fifth-line therapy (HRs for both, 0.9) but higher if it had been used as a third- or fourth-line therapy (HR of 1.4 for both).

“We often use tocilizumab as a second-line, third-line, or even fourth-line therapy, and if we don’t adjust for anything, we can have the impression that there are more infections with tocilizumab. But then, when we adjust for confounding factors and the line of therapy, we don’t have this anymore,” Dr. Lauper said.

“Line of therapy in itself is not a risk for serious infections,” she said in qualifying the conclusions that could be drawn from the study. “It may be a marker of the disease or some patient characteristic that is associated with a higher risk of infections.” Nevertheless, it should be taken into account when evaluating serious outcomes and possibly other safety and effectiveness outcomes.

“I understand concentrating on the hospitalized infections because the data are so much more robust,” observed consultant rheumatologist Jon Packham, BM, DM, of Haywood Hospital in Stoke-on-Trent, England, who chaired the session. He queried if there were any data on milder or just antibiotic-treated infections. At present, there aren’t those data to look at, Dr. Lauper responded, as this is something that’s difficult for registers to capture because doctors often do not log them in the databases.

There are also too few data on Janus kinase (JAK) inhibitors currently in the BSRBR-RA at present to be able to look at their rate of serious infection by line of therapy, Dr. Lauper noted. Because JAK inhibitors act on cytokines different from those affected by biologics for RA, there may be a difference there, but more data are needed on the JAK inhibitors before that question can be analyzed.

Dr. Lauper did not state having any disclosures. The BSRBR-RA is funded by the BSR via restricted income grants from several U.K. pharmaceutical companies, which has included or currently includes AbbVie, Celltrion, Hospira, Pfizer, UCB, Roche, Swedish Orphan Biovitrum, and Merck.

The prices of two new drugs that have been approved by the Food and Drug Administration for the treatment of lupus nephritis are in “reasonable alignment” with the drugs’ estimated benefits for patients with the disease, the Institute for Clinical and Economic Review has determined.

“Both belimumab [Benlysta] and voclosporin [Lupkynis] are important new treatment options,” Steven Pearson, MD, president of ICER, observed in a summary of the report’s findings.

“Despite remaining uncertainty about both treatments’ longer-term outcomes, their estimated net prices appear to be aligned with their anticipated clinical benefits. ... For patients and clinicians to have responsibly priced options specifically indicated for lupus nephritis is a win for patients and the entire health system,” Dr. Pearson added.

The estimated annual price of belimumab is approximately $43,000 per patient; the estimated annual price for voclosporin is approximately $92,000 per patient.

The incremental cost-effectiveness ratio for belimumab is approximately $90,0000 per quality-adjusted life-year; the corresponding value for voclosporin is higher, at approximately $149,000 per QALY, the ICER authors noted.

The report was published by ICER in April 2021.

Large unmet need for treatment of lupus nephritis

In their report, the ICER reviewed belimumab, a parenteral B-lymphocyte inhibitor, as well as voclosporin, an oral calcineurin inhibitor, as initial treatment of patients with lupus nephritis. Lupus nephritis is a serious complication of systemic lupus erythematosus (SLE).

Belimumab was first approved for the treatment of lupus in adults in the United States in March 2011. In April 2019, it was approved for use for the same indication for children aged 5 years and older. The FDA expanded the indication in December 2020 to include adults with active lupus nephritis who are receiving standard therapy.

Voclosporin was approved for the treatment of lupus nephritis in January 2021.

In the pivotal trials for the two agents, each drug was added to standard induction therapy for lupus nephritis, which consisted of high-dose corticosteroids combined with either mycophenolate mofetil (MMF) or cyclophosphamide.

Compared with standard therapy alone, belimumab increased the complete renal response and the primary efficacy renal response at 2 years. With voclosporin, complete response was nearly doubled, and there was marked increased in partial response at 1 year, compared with standard therapy alone.

Neither drug appeared to increase the adverse-event rate or the rate of discontinuations, compared with standard therapy, although the FDA did add a black box warning regarding the possible risk for serious infections and malignancies with voclosporin use.

“There is a very large unmet need for the treatment of lupus nephritis,” Chris Phillips, MD, of Paducah (Ky.) Rheumatology said in an interview.

“A very large percentage of patients who do not achieve complete remission on traditional treatments have side effects or contraindications to these treatments, so we’ve needed new ones for sure,” he stressed.

The ICER authors made it clear that there is considerable uncertainty as to how short-term assessment of each of the two drugs’ performance might translate into meaningful long-term outcomes for patients, especially given that SLE is a lifelong illness.

On the other hand, “there are a lot of attributes for both of these new drugs that suggest there is potential for kidney benefit over time,” Brad Rovin, MD, professor of medicine and pathology at the Ohio State University Wexner Medical Center, Columbus, said in an interview.

For example, data from the BLISS-LN study, reported by Dr. Rovin during a meeting last year, suggest that belimumab reduces the flare rate and appears to stabilize kidney function over time, compared with standard therapy alone.

“BLISS-LN was 2 years long, so it gave us an opportunity to look at kidney function over a longer period of time than most of our prior trials in lupus nephritis,” he explained.

“The stabilization of kidney function is important, because it suggests that belimumab has a kidney protective effect, while a decrease in lupus nephritis flares is also important, because each time the disease flares, you can accumulate chronic tissue damage, which can eventually cause end-stage renal disease [ESRD],” he said.

Dr. Rovin also pointed out that the BLISS-LN trial results indicate that patients who achieve a urine protein level less than 700 mg/d after the first year of treatment do very well on long-term follow-up – another hint that belimumab may have long-term benefits for kidney function.

Voclosporin is a calcineurin inhibitor, which are protective of podocytes. “When you start to lose too many podocytes, the kidney can again progress onto ESRD, so this is again an extra benefit of the calcineurin inhibitors in the context of kidney disease that affects the glomeruli,” he noted.

“So both of these drugs have these interesting attributes that go beyond, or at least are maybe tied to, their immunosuppressive actions, but they do offer some kidney protective effects,” he reaffirmed.
 

Black patients underrepresented in trials

The ICER authors voiced concern over the fact that individuals most at risk for SLE – mostly Black patients, but also patients of other racial groups – were underrepresented in clinical trials that evaluated both agents.

“We cannot stress enough that the results are highly uncertain due to the small numbers of Black patients in the available clinical trials and the lack of data on differences among subgroups in long-term outcomes,” they stated.

This is not an academic issue, Dr. Phillips pointed out. Responses to both MMF and cyclophosphamide differ among persons of different races, “so it’s not unreasonable to consider that there could be racial differences in treatment responses to both drugs, and these definitely need to be investigated.”

This is not an academic issue, Dr. Phillips said, because there are racial disparities in how patients respond to both MMF and cyclophosphamide – “so it’s not unreasonable to consider that there could be racial differences in treatment responses to both drugs, and these definitely need to be investigated.”

The ICER authors appear to agree. They urged the manufacturers of the two new agents to expand their research to include adequate representation of lupus nephritis patients from Black and other non-White communities.

However, it is somewhat reassuring that the pivotal voclosporin trial enrolled about 30% of Hispanic patients and that about 17% of participants in the BLISS-LN trial were also Hispanic, Dr. Rovin pointed out.

This is important because Hispanic patients can have very aggressive disease, as can Black patients, he noted. There is some evidence to suggest both drugs are effective in aggressive disease.

The ICER also pointed out that the length of time that both drugs can be used prior to tapering of treatment, after which patients receive standard maintenance therapy alone, has yet to be established.

This is important, Dr. Rovin and Dr. Phillips agreed, because calcineurin inhibitors are known to be nephrotoxic, and both drugs are immunosuppressive. At least with respect to voclosporin, there is some cause of concern regarding prolonged use of the drug for patients with kidney disease.

“We don’t want patients to be on an immunosuppressive drug forever if they don’t need to be,” Dr. Rovin emphasized.

“But we are seeing really long-term remission in the setting of other inflammatory diseases, like vasculitis with rituximab. So there is hope that we can achieve the same thing in lupus. If we use drugs that target T cells in the immune system, like voclosporin, or B cells, like belimumab, maybe we can ‘reset’ the immune system and get rid of potentially autoreactive cells that could allow long-lasting disease remission, which is an unanswered question but an intriguing possibility,” he concluded.

Dr. Rovin has served as a consultant for GlaxoSmithKline. Dr. Phillips disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The prices of two new drugs that have been approved by the Food and Drug Administration for the treatment of lupus nephritis are in “reasonable alignment” with the drugs’ estimated benefits for patients with the disease, the Institute for Clinical and Economic Review has determined.

“Both belimumab [Benlysta] and voclosporin [Lupkynis] are important new treatment options,” Steven Pearson, MD, president of ICER, observed in a summary of the report’s findings.

“Despite remaining uncertainty about both treatments’ longer-term outcomes, their estimated net prices appear to be aligned with their anticipated clinical benefits. ... For patients and clinicians to have responsibly priced options specifically indicated for lupus nephritis is a win for patients and the entire health system,” Dr. Pearson added.

The estimated annual price of belimumab is approximately $43,000 per patient; the estimated annual price for voclosporin is approximately $92,000 per patient.

The incremental cost-effectiveness ratio for belimumab is approximately $90,0000 per quality-adjusted life-year; the corresponding value for voclosporin is higher, at approximately $149,000 per QALY, the ICER authors noted.

The report was published by ICER in April 2021.

Large unmet need for treatment of lupus nephritis

In their report, the ICER reviewed belimumab, a parenteral B-lymphocyte inhibitor, as well as voclosporin, an oral calcineurin inhibitor, as initial treatment of patients with lupus nephritis. Lupus nephritis is a serious complication of systemic lupus erythematosus (SLE).

Belimumab was first approved for the treatment of lupus in adults in the United States in March 2011. In April 2019, it was approved for use for the same indication for children aged 5 years and older. The FDA expanded the indication in December 2020 to include adults with active lupus nephritis who are receiving standard therapy.

Voclosporin was approved for the treatment of lupus nephritis in January 2021.

In the pivotal trials for the two agents, each drug was added to standard induction therapy for lupus nephritis, which consisted of high-dose corticosteroids combined with either mycophenolate mofetil (MMF) or cyclophosphamide.

Compared with standard therapy alone, belimumab increased the complete renal response and the primary efficacy renal response at 2 years. With voclosporin, complete response was nearly doubled, and there was marked increased in partial response at 1 year, compared with standard therapy alone.

Neither drug appeared to increase the adverse-event rate or the rate of discontinuations, compared with standard therapy, although the FDA did add a black box warning regarding the possible risk for serious infections and malignancies with voclosporin use.

“There is a very large unmet need for the treatment of lupus nephritis,” Chris Phillips, MD, of Paducah (Ky.) Rheumatology said in an interview.

“A very large percentage of patients who do not achieve complete remission on traditional treatments have side effects or contraindications to these treatments, so we’ve needed new ones for sure,” he stressed.

The ICER authors made it clear that there is considerable uncertainty as to how short-term assessment of each of the two drugs’ performance might translate into meaningful long-term outcomes for patients, especially given that SLE is a lifelong illness.

On the other hand, “there are a lot of attributes for both of these new drugs that suggest there is potential for kidney benefit over time,” Brad Rovin, MD, professor of medicine and pathology at the Ohio State University Wexner Medical Center, Columbus, said in an interview.

For example, data from the BLISS-LN study, reported by Dr. Rovin during a meeting last year, suggest that belimumab reduces the flare rate and appears to stabilize kidney function over time, compared with standard therapy alone.

“BLISS-LN was 2 years long, so it gave us an opportunity to look at kidney function over a longer period of time than most of our prior trials in lupus nephritis,” he explained.

“The stabilization of kidney function is important, because it suggests that belimumab has a kidney protective effect, while a decrease in lupus nephritis flares is also important, because each time the disease flares, you can accumulate chronic tissue damage, which can eventually cause end-stage renal disease [ESRD],” he said.

Dr. Rovin also pointed out that the BLISS-LN trial results indicate that patients who achieve a urine protein level less than 700 mg/d after the first year of treatment do very well on long-term follow-up – another hint that belimumab may have long-term benefits for kidney function.

Voclosporin is a calcineurin inhibitor, which are protective of podocytes. “When you start to lose too many podocytes, the kidney can again progress onto ESRD, so this is again an extra benefit of the calcineurin inhibitors in the context of kidney disease that affects the glomeruli,” he noted.

“So both of these drugs have these interesting attributes that go beyond, or at least are maybe tied to, their immunosuppressive actions, but they do offer some kidney protective effects,” he reaffirmed.
 

Black patients underrepresented in trials

The ICER authors voiced concern over the fact that individuals most at risk for SLE – mostly Black patients, but also patients of other racial groups – were underrepresented in clinical trials that evaluated both agents.

“We cannot stress enough that the results are highly uncertain due to the small numbers of Black patients in the available clinical trials and the lack of data on differences among subgroups in long-term outcomes,” they stated.

This is not an academic issue, Dr. Phillips pointed out. Responses to both MMF and cyclophosphamide differ among persons of different races, “so it’s not unreasonable to consider that there could be racial differences in treatment responses to both drugs, and these definitely need to be investigated.”

This is not an academic issue, Dr. Phillips said, because there are racial disparities in how patients respond to both MMF and cyclophosphamide – “so it’s not unreasonable to consider that there could be racial differences in treatment responses to both drugs, and these definitely need to be investigated.”

The ICER authors appear to agree. They urged the manufacturers of the two new agents to expand their research to include adequate representation of lupus nephritis patients from Black and other non-White communities.

However, it is somewhat reassuring that the pivotal voclosporin trial enrolled about 30% of Hispanic patients and that about 17% of participants in the BLISS-LN trial were also Hispanic, Dr. Rovin pointed out.

This is important because Hispanic patients can have very aggressive disease, as can Black patients, he noted. There is some evidence to suggest both drugs are effective in aggressive disease.

The ICER also pointed out that the length of time that both drugs can be used prior to tapering of treatment, after which patients receive standard maintenance therapy alone, has yet to be established.

This is important, Dr. Rovin and Dr. Phillips agreed, because calcineurin inhibitors are known to be nephrotoxic, and both drugs are immunosuppressive. At least with respect to voclosporin, there is some cause of concern regarding prolonged use of the drug for patients with kidney disease.

“We don’t want patients to be on an immunosuppressive drug forever if they don’t need to be,” Dr. Rovin emphasized.

“But we are seeing really long-term remission in the setting of other inflammatory diseases, like vasculitis with rituximab. So there is hope that we can achieve the same thing in lupus. If we use drugs that target T cells in the immune system, like voclosporin, or B cells, like belimumab, maybe we can ‘reset’ the immune system and get rid of potentially autoreactive cells that could allow long-lasting disease remission, which is an unanswered question but an intriguing possibility,” he concluded.

Dr. Rovin has served as a consultant for GlaxoSmithKline. Dr. Phillips disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The prices of two new drugs that have been approved by the Food and Drug Administration for the treatment of lupus nephritis are in “reasonable alignment” with the drugs’ estimated benefits for patients with the disease, the Institute for Clinical and Economic Review has determined.

“Both belimumab [Benlysta] and voclosporin [Lupkynis] are important new treatment options,” Steven Pearson, MD, president of ICER, observed in a summary of the report’s findings.

“Despite remaining uncertainty about both treatments’ longer-term outcomes, their estimated net prices appear to be aligned with their anticipated clinical benefits. ... For patients and clinicians to have responsibly priced options specifically indicated for lupus nephritis is a win for patients and the entire health system,” Dr. Pearson added.

The estimated annual price of belimumab is approximately $43,000 per patient; the estimated annual price for voclosporin is approximately $92,000 per patient.

The incremental cost-effectiveness ratio for belimumab is approximately $90,0000 per quality-adjusted life-year; the corresponding value for voclosporin is higher, at approximately $149,000 per QALY, the ICER authors noted.

The report was published by ICER in April 2021.

Large unmet need for treatment of lupus nephritis

In their report, the ICER reviewed belimumab, a parenteral B-lymphocyte inhibitor, as well as voclosporin, an oral calcineurin inhibitor, as initial treatment of patients with lupus nephritis. Lupus nephritis is a serious complication of systemic lupus erythematosus (SLE).

Belimumab was first approved for the treatment of lupus in adults in the United States in March 2011. In April 2019, it was approved for use for the same indication for children aged 5 years and older. The FDA expanded the indication in December 2020 to include adults with active lupus nephritis who are receiving standard therapy.

Voclosporin was approved for the treatment of lupus nephritis in January 2021.

In the pivotal trials for the two agents, each drug was added to standard induction therapy for lupus nephritis, which consisted of high-dose corticosteroids combined with either mycophenolate mofetil (MMF) or cyclophosphamide.

Compared with standard therapy alone, belimumab increased the complete renal response and the primary efficacy renal response at 2 years. With voclosporin, complete response was nearly doubled, and there was marked increased in partial response at 1 year, compared with standard therapy alone.

Neither drug appeared to increase the adverse-event rate or the rate of discontinuations, compared with standard therapy, although the FDA did add a black box warning regarding the possible risk for serious infections and malignancies with voclosporin use.

“There is a very large unmet need for the treatment of lupus nephritis,” Chris Phillips, MD, of Paducah (Ky.) Rheumatology said in an interview.

“A very large percentage of patients who do not achieve complete remission on traditional treatments have side effects or contraindications to these treatments, so we’ve needed new ones for sure,” he stressed.

The ICER authors made it clear that there is considerable uncertainty as to how short-term assessment of each of the two drugs’ performance might translate into meaningful long-term outcomes for patients, especially given that SLE is a lifelong illness.

On the other hand, “there are a lot of attributes for both of these new drugs that suggest there is potential for kidney benefit over time,” Brad Rovin, MD, professor of medicine and pathology at the Ohio State University Wexner Medical Center, Columbus, said in an interview.

For example, data from the BLISS-LN study, reported by Dr. Rovin during a meeting last year, suggest that belimumab reduces the flare rate and appears to stabilize kidney function over time, compared with standard therapy alone.

“BLISS-LN was 2 years long, so it gave us an opportunity to look at kidney function over a longer period of time than most of our prior trials in lupus nephritis,” he explained.

“The stabilization of kidney function is important, because it suggests that belimumab has a kidney protective effect, while a decrease in lupus nephritis flares is also important, because each time the disease flares, you can accumulate chronic tissue damage, which can eventually cause end-stage renal disease [ESRD],” he said.

Dr. Rovin also pointed out that the BLISS-LN trial results indicate that patients who achieve a urine protein level less than 700 mg/d after the first year of treatment do very well on long-term follow-up – another hint that belimumab may have long-term benefits for kidney function.

Voclosporin is a calcineurin inhibitor, which are protective of podocytes. “When you start to lose too many podocytes, the kidney can again progress onto ESRD, so this is again an extra benefit of the calcineurin inhibitors in the context of kidney disease that affects the glomeruli,” he noted.

“So both of these drugs have these interesting attributes that go beyond, or at least are maybe tied to, their immunosuppressive actions, but they do offer some kidney protective effects,” he reaffirmed.
 

Black patients underrepresented in trials

The ICER authors voiced concern over the fact that individuals most at risk for SLE – mostly Black patients, but also patients of other racial groups – were underrepresented in clinical trials that evaluated both agents.

“We cannot stress enough that the results are highly uncertain due to the small numbers of Black patients in the available clinical trials and the lack of data on differences among subgroups in long-term outcomes,” they stated.

This is not an academic issue, Dr. Phillips pointed out. Responses to both MMF and cyclophosphamide differ among persons of different races, “so it’s not unreasonable to consider that there could be racial differences in treatment responses to both drugs, and these definitely need to be investigated.”

This is not an academic issue, Dr. Phillips said, because there are racial disparities in how patients respond to both MMF and cyclophosphamide – “so it’s not unreasonable to consider that there could be racial differences in treatment responses to both drugs, and these definitely need to be investigated.”

The ICER authors appear to agree. They urged the manufacturers of the two new agents to expand their research to include adequate representation of lupus nephritis patients from Black and other non-White communities.

However, it is somewhat reassuring that the pivotal voclosporin trial enrolled about 30% of Hispanic patients and that about 17% of participants in the BLISS-LN trial were also Hispanic, Dr. Rovin pointed out.

This is important because Hispanic patients can have very aggressive disease, as can Black patients, he noted. There is some evidence to suggest both drugs are effective in aggressive disease.

The ICER also pointed out that the length of time that both drugs can be used prior to tapering of treatment, after which patients receive standard maintenance therapy alone, has yet to be established.

This is important, Dr. Rovin and Dr. Phillips agreed, because calcineurin inhibitors are known to be nephrotoxic, and both drugs are immunosuppressive. At least with respect to voclosporin, there is some cause of concern regarding prolonged use of the drug for patients with kidney disease.

“We don’t want patients to be on an immunosuppressive drug forever if they don’t need to be,” Dr. Rovin emphasized.

“But we are seeing really long-term remission in the setting of other inflammatory diseases, like vasculitis with rituximab. So there is hope that we can achieve the same thing in lupus. If we use drugs that target T cells in the immune system, like voclosporin, or B cells, like belimumab, maybe we can ‘reset’ the immune system and get rid of potentially autoreactive cells that could allow long-lasting disease remission, which is an unanswered question but an intriguing possibility,” he concluded.

Dr. Rovin has served as a consultant for GlaxoSmithKline. Dr. Phillips disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Studies are flagging racial and ethnic disparities in rheumatology training materials, pointing to a need to boost representation of darker skin tones and better educate physicians in evaluating this cohort.

AndreyPopov/Getty Images

Not enough is known about these disparities in rheumatology education, despite the fact that minorities make up 40% of the population in the United States.

The problem starts with books and references used in medical schools, Lynn McKinley-Grant, MD, immediate past president of the Skin of Color Society and associate professor of dermatology at Howard University, Washington, said in an interview. “In the medical literature there has been a dearth of images in skin of color in all specialties,” she said. With an increased diversity in the U.S. population, there is a need for health care providers to be able to recognize disease patterns in all skin types.” If a physician is training at an institution where there are not many patients of color in the community, the rheumatologists are even more limited in terms of their clinical experience.

This lack of training in diagnosis of disease has serious clinical repercussions, as seen in COVID cases, Dr. McKinley-Grant noted. “You end up not being able to recognize early erythema, jaundice, anemia, or hypoxemia because those conditions are a different color or pattern in the darker skin types. This can lead to errors in treatment, diagnosis, and medical care, resulting in increased morbidity and mortality.”

Studies point to education gaps

A team of researchers from Washington University in St. Louis called attention to this issue at the American College of Rhematology’s Convergence 2020 conference.

“Patients of color with lupus are especially vulnerable as they often carry a greater disease burden, yet studies show that individuals with darker skin tones are underrepresented in medical educational materials,” Vijay Kannuthurai, MD, and colleagues wrote in their study abstract. The team surveyed 132 providers in St. Louis, Mo., on their confidence in evaluating any rash, and rashes in patients with lupus and varied skin tones.

Participating clinicians, mostly rheumatologists, dermatologists, or internists, had a higher confidence level in diagnosing any rash versus lupus rashes, but were considerably less confident in diagnosing lupus rash on darker skin, compared with those on fair skin. This represents “a disparity between provider confidence and the patient population lupus traditionally affects,” the investigators concluded.

Another recent study found evidence of disparities in clinical education resources. “The lack of dark skin representation among rheumatology educational materials contributes to the implicit bias and structural racism present in medical education by promoting White-only models of disease,” lead author Adrienne Strait, a medical student at the University of California, San Francisco, said in an interview. “Given that rheumatic diseases disproportionately impact racial and ethnic minorities, we felt it was important to examine the representation of these groups within rheumatology training resources.”

She and her colleagues gathered images of rheumatic diseases from four major databases: the American College of Rheumatology’s Image Library, UpToDate, the New England Journal of Medicine Images in Clinical Medicine and Clinical Cases filtered by “Rheumatology,” and the 9th edition of Kelley’s Textbook of Rheumatology. They used Fitzpatrick’s skin phototypes to independently code images depicting skin as “light” (skin types I-IV), “dark” (skin types V-VI), or “indeterminate,” focusing on systemic lupus erythematosus (SLE) and rheumatoid arthritis, two conditions with a known connection to racial and ethnic health disparities.

Taking into account the high incidence of sarcoidosis and SLE in Black patients when compared with White patients, the investigators did a secondary analysis that excluded these cases.

Among 1,043 patient images studied, just 13.4% represented dark skin, compared with 84% that represented light skin. More than 2% represented an indeterminate skin color. Comparing dark-skin representation in the clinical images and SLE images with the representation of Asian, Native American, and Black individuals in the United States and within lupus cases nationally, the investigators found significant underrepresentation of dark skin.

Only 4.2% of RA images had dark-skin representation, making RA one of the diseases with the lowest representation in the study, along with juvenile idiopathic arthritis, the spondyloarthropathies, and Kawasaki disease. “Representation of dark skin in SLE was also lower than the proportion of Black individuals in SLE studies,” the investigators noted. Overall, representation of dark skin in SLE images was just 22.6%. Sarcoidosis comparatively had the largest representation of dark-skin images (69.6%, n = 32).

“Excluding sarcoidosis and SLE images, the overall representation of dark skin was 9.4% (n = 84), which was significantly lower than the proportion of Asian, Native American, and Black individuals within the U.S. Census population,” according to Ms. Strait and her associates. UpToDate contained the largest proportion of images of dark skin respective to other databases, whereas Kelley’s Textbook had the smallest.
 

Actionable steps

Many physicians are willing to improve upon their skills in identifying conditions on darker skin, as the study by Dr. Kannuthurai and associates suggests. Overall, 93% of the survey’s participants wanted to learn more about rashes in patients of color. “Future educational interventions may help practitioners improve their confidence when diagnosing rashes in lupus patients” with darker skin, they suggested.

Ms. Strait and her colleagues recommended a series of actionable steps to improve diversity and equity of dark skin tone representation in rheumatology curricula.

Editors of educational resources, for example, should make image diversity a priority for those diseases that are most commonly associated with cutaneous manifestations, such as SLE, vasculitis, inflammatory myopathies, systemic sclerosis, sarcoidosis, and psoriasis. They also called for educators in academic rheumatology programs to collaborate to improve diversity in resources used at the undergraduate and graduate medical education level.

Efforts should take place at the local, regional, and national level to publicly discuss and educate clinicians about rheumatic diseases in individuals of color. Speakers at rheumatology conferences should strive to educate learners about presentations of rheumatic diseases in individuals of color. The ACR in the meantime could establish a task force to enhance racial and ethnic diversity in their image library and other published resources.

“These steps may improve provider recognition and diagnosis of rheumatic disease manifestations in skin of color, which may in turn reduce health disparities among racial and ethnic minority groups,” Ms. Strait said.

Beth L. Jonas, MD, chair of the ACR’s Committee on Rheumatology Training and Workforce Issues, called the findings of this study “timely and important.” The researchers highlighted a deficiency in rheumatology training materials that needs addressing, she said in an interview. “I definitely agree that ACR needs to be mindful of this. There’s no doubt that we need to take these recommendations and move along these lines.”

The ACR took a first step in 2020 with the creation of a diversity, equity, and inclusion committee. “We are undergoing a college-wide look at what we do, with an eye toward inclusion. There is a strong interest in addressing health disparities and being an equitable and inclusive community of rheumatology health care professionals,” said Dr. Jonas, chief of the University of North Carolina at Chapel Hill’s division of rheumatology, allergy, and immunology.

The American Academy of Dermatology is also working to improve the image library with images of disease in skin of color. “Everyone’s jumping on this now,” Dr. McKinley-Grant observed. The medical profession can’t afford not to. It’s a life-threatening issue when rheumatoid arthritis and other diseases in people of color aren’t diagnosed early and correctly, she added.

Technologies seek to reduce bias

While many organizations are taking steps to improve representation of darker skin images, VisualDx has taken the lead on this, she said. “They’ve been doing this for years now. There are over 14,000 images of disease in skin of color, including all the rheumatologic diseases. There’s a mobile app and desktop decision support system, and it is very popular. A majority of medical schools have this as a library resource, and hospital systems license it for EHR integration.” Doctors can also get it individually. This enables them to share images and handouts of a diagnosis and select images of patients of color, said Dr. McKinley-Grant, who uses the VisualDx smartphone app DermExpert, which is an app for nondermatologists that features an image library of skin lesions, including darker-skin images.

ProjectIMPACT, powered by VisualDx, is another effort to support reducing health care bias in darker skin. The project is a collaboration between the New England Journal of Medicine Group and the Skin Of Color Society. According to Dr. McKinley-Grant, the organizers are building awareness of the importance of reducing the educational and clinical gaps in diagnosing patients of color and trying to get students and educators to pledge to take meaningful steps and to have real-world impact.

This isn’t just exclusive to dermatology and rheumatology – it involves all medical specialties, she stressed.

ProjectIMPACT isn’t just a resource for physicians, she continued. Librarians can also use it to develop more resources on skin of color.

The Skin Of Color Society and VisualDx have also partnered with the NEJM Group to develop a comprehensive virtual series on the impact of skin color and ethnicity on clinical research. The four-part series addresses structural racism and racial bias in medicine, hair disorders in people of color, pigmentary disorders, keloids, COVID-19 comorbidities, and cutaneous manifestations of systemic diseases in children and adults.

Nuances of recognizing disease

As a medical student, Dr. McKinley-Grant said she was fortunate to attend the Albert Schweitzer Hospital in Lambarene, Gabon, on a fellowship. For 3 months, she gained a wealth of experience examining only African patients with brown skin.

In her other training in medicine, “I’ve been at institutions with diverse populations, in Boston, New York, and Washington,” learning more about all different skin pigments.

This type of training should be more widely available, especially now, with COVID-19 producing new manifestations of skin lesions, she emphasized. Such efforts involve a diversification of images physicians are being trained on so that they can recognize the same disease in a person of color.

“Doctors have to be able to recognize different colors, different shades of brown and shades of white. Not all white skin is the same color,” she noted. In looking at a rash or lesion, “you have to learn how to discern differences in the background color of the skin, which is determined by melanin in the skin (Fitzpatrick skin types I-VI) and by what’s going on in the blood, such as how much oxygen and hemoglobin the patient has in their blood.” Inflammation and infection (erythema) will appear more violaceous in IV-VI skin types, for example.

At the University of North Carolina at Chapel Hill, a group of students and faculty have created a dermatology image library to address the deficiency in the availability of images for teaching purposes. “Our medical students recognized the gap and started this,” Dr. Jonas said. Julie Mervak, MD, assistant professor of dermatology, is spearheading this effort, with students Linnea Westerkam and Anuj Pranav Sanghvi.

“I understand that others around the country are working on similar initiatives,” Dr. Jonas said.

None of the sources for this story had any relevant disclosures.

Studies are flagging racial and ethnic disparities in rheumatology training materials, pointing to a need to boost representation of darker skin tones and better educate physicians in evaluating this cohort.

AndreyPopov/Getty Images

Not enough is known about these disparities in rheumatology education, despite the fact that minorities make up 40% of the population in the United States.

The problem starts with books and references used in medical schools, Lynn McKinley-Grant, MD, immediate past president of the Skin of Color Society and associate professor of dermatology at Howard University, Washington, said in an interview. “In the medical literature there has been a dearth of images in skin of color in all specialties,” she said. With an increased diversity in the U.S. population, there is a need for health care providers to be able to recognize disease patterns in all skin types.” If a physician is training at an institution where there are not many patients of color in the community, the rheumatologists are even more limited in terms of their clinical experience.

This lack of training in diagnosis of disease has serious clinical repercussions, as seen in COVID cases, Dr. McKinley-Grant noted. “You end up not being able to recognize early erythema, jaundice, anemia, or hypoxemia because those conditions are a different color or pattern in the darker skin types. This can lead to errors in treatment, diagnosis, and medical care, resulting in increased morbidity and mortality.”

Studies point to education gaps

A team of researchers from Washington University in St. Louis called attention to this issue at the American College of Rhematology’s Convergence 2020 conference.

“Patients of color with lupus are especially vulnerable as they often carry a greater disease burden, yet studies show that individuals with darker skin tones are underrepresented in medical educational materials,” Vijay Kannuthurai, MD, and colleagues wrote in their study abstract. The team surveyed 132 providers in St. Louis, Mo., on their confidence in evaluating any rash, and rashes in patients with lupus and varied skin tones.

Participating clinicians, mostly rheumatologists, dermatologists, or internists, had a higher confidence level in diagnosing any rash versus lupus rashes, but were considerably less confident in diagnosing lupus rash on darker skin, compared with those on fair skin. This represents “a disparity between provider confidence and the patient population lupus traditionally affects,” the investigators concluded.

Another recent study found evidence of disparities in clinical education resources. “The lack of dark skin representation among rheumatology educational materials contributes to the implicit bias and structural racism present in medical education by promoting White-only models of disease,” lead author Adrienne Strait, a medical student at the University of California, San Francisco, said in an interview. “Given that rheumatic diseases disproportionately impact racial and ethnic minorities, we felt it was important to examine the representation of these groups within rheumatology training resources.”

She and her colleagues gathered images of rheumatic diseases from four major databases: the American College of Rheumatology’s Image Library, UpToDate, the New England Journal of Medicine Images in Clinical Medicine and Clinical Cases filtered by “Rheumatology,” and the 9th edition of Kelley’s Textbook of Rheumatology. They used Fitzpatrick’s skin phototypes to independently code images depicting skin as “light” (skin types I-IV), “dark” (skin types V-VI), or “indeterminate,” focusing on systemic lupus erythematosus (SLE) and rheumatoid arthritis, two conditions with a known connection to racial and ethnic health disparities.

Taking into account the high incidence of sarcoidosis and SLE in Black patients when compared with White patients, the investigators did a secondary analysis that excluded these cases.

Among 1,043 patient images studied, just 13.4% represented dark skin, compared with 84% that represented light skin. More than 2% represented an indeterminate skin color. Comparing dark-skin representation in the clinical images and SLE images with the representation of Asian, Native American, and Black individuals in the United States and within lupus cases nationally, the investigators found significant underrepresentation of dark skin.

Only 4.2% of RA images had dark-skin representation, making RA one of the diseases with the lowest representation in the study, along with juvenile idiopathic arthritis, the spondyloarthropathies, and Kawasaki disease. “Representation of dark skin in SLE was also lower than the proportion of Black individuals in SLE studies,” the investigators noted. Overall, representation of dark skin in SLE images was just 22.6%. Sarcoidosis comparatively had the largest representation of dark-skin images (69.6%, n = 32).

“Excluding sarcoidosis and SLE images, the overall representation of dark skin was 9.4% (n = 84), which was significantly lower than the proportion of Asian, Native American, and Black individuals within the U.S. Census population,” according to Ms. Strait and her associates. UpToDate contained the largest proportion of images of dark skin respective to other databases, whereas Kelley’s Textbook had the smallest.
 

Actionable steps

Many physicians are willing to improve upon their skills in identifying conditions on darker skin, as the study by Dr. Kannuthurai and associates suggests. Overall, 93% of the survey’s participants wanted to learn more about rashes in patients of color. “Future educational interventions may help practitioners improve their confidence when diagnosing rashes in lupus patients” with darker skin, they suggested.

Ms. Strait and her colleagues recommended a series of actionable steps to improve diversity and equity of dark skin tone representation in rheumatology curricula.

Editors of educational resources, for example, should make image diversity a priority for those diseases that are most commonly associated with cutaneous manifestations, such as SLE, vasculitis, inflammatory myopathies, systemic sclerosis, sarcoidosis, and psoriasis. They also called for educators in academic rheumatology programs to collaborate to improve diversity in resources used at the undergraduate and graduate medical education level.

Efforts should take place at the local, regional, and national level to publicly discuss and educate clinicians about rheumatic diseases in individuals of color. Speakers at rheumatology conferences should strive to educate learners about presentations of rheumatic diseases in individuals of color. The ACR in the meantime could establish a task force to enhance racial and ethnic diversity in their image library and other published resources.

“These steps may improve provider recognition and diagnosis of rheumatic disease manifestations in skin of color, which may in turn reduce health disparities among racial and ethnic minority groups,” Ms. Strait said.

Beth L. Jonas, MD, chair of the ACR’s Committee on Rheumatology Training and Workforce Issues, called the findings of this study “timely and important.” The researchers highlighted a deficiency in rheumatology training materials that needs addressing, she said in an interview. “I definitely agree that ACR needs to be mindful of this. There’s no doubt that we need to take these recommendations and move along these lines.”

The ACR took a first step in 2020 with the creation of a diversity, equity, and inclusion committee. “We are undergoing a college-wide look at what we do, with an eye toward inclusion. There is a strong interest in addressing health disparities and being an equitable and inclusive community of rheumatology health care professionals,” said Dr. Jonas, chief of the University of North Carolina at Chapel Hill’s division of rheumatology, allergy, and immunology.

The American Academy of Dermatology is also working to improve the image library with images of disease in skin of color. “Everyone’s jumping on this now,” Dr. McKinley-Grant observed. The medical profession can’t afford not to. It’s a life-threatening issue when rheumatoid arthritis and other diseases in people of color aren’t diagnosed early and correctly, she added.

Technologies seek to reduce bias

While many organizations are taking steps to improve representation of darker skin images, VisualDx has taken the lead on this, she said. “They’ve been doing this for years now. There are over 14,000 images of disease in skin of color, including all the rheumatologic diseases. There’s a mobile app and desktop decision support system, and it is very popular. A majority of medical schools have this as a library resource, and hospital systems license it for EHR integration.” Doctors can also get it individually. This enables them to share images and handouts of a diagnosis and select images of patients of color, said Dr. McKinley-Grant, who uses the VisualDx smartphone app DermExpert, which is an app for nondermatologists that features an image library of skin lesions, including darker-skin images.

ProjectIMPACT, powered by VisualDx, is another effort to support reducing health care bias in darker skin. The project is a collaboration between the New England Journal of Medicine Group and the Skin Of Color Society. According to Dr. McKinley-Grant, the organizers are building awareness of the importance of reducing the educational and clinical gaps in diagnosing patients of color and trying to get students and educators to pledge to take meaningful steps and to have real-world impact.

This isn’t just exclusive to dermatology and rheumatology – it involves all medical specialties, she stressed.

ProjectIMPACT isn’t just a resource for physicians, she continued. Librarians can also use it to develop more resources on skin of color.

The Skin Of Color Society and VisualDx have also partnered with the NEJM Group to develop a comprehensive virtual series on the impact of skin color and ethnicity on clinical research. The four-part series addresses structural racism and racial bias in medicine, hair disorders in people of color, pigmentary disorders, keloids, COVID-19 comorbidities, and cutaneous manifestations of systemic diseases in children and adults.

Nuances of recognizing disease

As a medical student, Dr. McKinley-Grant said she was fortunate to attend the Albert Schweitzer Hospital in Lambarene, Gabon, on a fellowship. For 3 months, she gained a wealth of experience examining only African patients with brown skin.

In her other training in medicine, “I’ve been at institutions with diverse populations, in Boston, New York, and Washington,” learning more about all different skin pigments.

This type of training should be more widely available, especially now, with COVID-19 producing new manifestations of skin lesions, she emphasized. Such efforts involve a diversification of images physicians are being trained on so that they can recognize the same disease in a person of color.

“Doctors have to be able to recognize different colors, different shades of brown and shades of white. Not all white skin is the same color,” she noted. In looking at a rash or lesion, “you have to learn how to discern differences in the background color of the skin, which is determined by melanin in the skin (Fitzpatrick skin types I-VI) and by what’s going on in the blood, such as how much oxygen and hemoglobin the patient has in their blood.” Inflammation and infection (erythema) will appear more violaceous in IV-VI skin types, for example.

At the University of North Carolina at Chapel Hill, a group of students and faculty have created a dermatology image library to address the deficiency in the availability of images for teaching purposes. “Our medical students recognized the gap and started this,” Dr. Jonas said. Julie Mervak, MD, assistant professor of dermatology, is spearheading this effort, with students Linnea Westerkam and Anuj Pranav Sanghvi.

“I understand that others around the country are working on similar initiatives,” Dr. Jonas said.

None of the sources for this story had any relevant disclosures.

Studies are flagging racial and ethnic disparities in rheumatology training materials, pointing to a need to boost representation of darker skin tones and better educate physicians in evaluating this cohort.

AndreyPopov/Getty Images

Not enough is known about these disparities in rheumatology education, despite the fact that minorities make up 40% of the population in the United States.

The problem starts with books and references used in medical schools, Lynn McKinley-Grant, MD, immediate past president of the Skin of Color Society and associate professor of dermatology at Howard University, Washington, said in an interview. “In the medical literature there has been a dearth of images in skin of color in all specialties,” she said. With an increased diversity in the U.S. population, there is a need for health care providers to be able to recognize disease patterns in all skin types.” If a physician is training at an institution where there are not many patients of color in the community, the rheumatologists are even more limited in terms of their clinical experience.

This lack of training in diagnosis of disease has serious clinical repercussions, as seen in COVID cases, Dr. McKinley-Grant noted. “You end up not being able to recognize early erythema, jaundice, anemia, or hypoxemia because those conditions are a different color or pattern in the darker skin types. This can lead to errors in treatment, diagnosis, and medical care, resulting in increased morbidity and mortality.”

Studies point to education gaps

A team of researchers from Washington University in St. Louis called attention to this issue at the American College of Rhematology’s Convergence 2020 conference.

“Patients of color with lupus are especially vulnerable as they often carry a greater disease burden, yet studies show that individuals with darker skin tones are underrepresented in medical educational materials,” Vijay Kannuthurai, MD, and colleagues wrote in their study abstract. The team surveyed 132 providers in St. Louis, Mo., on their confidence in evaluating any rash, and rashes in patients with lupus and varied skin tones.

Participating clinicians, mostly rheumatologists, dermatologists, or internists, had a higher confidence level in diagnosing any rash versus lupus rashes, but were considerably less confident in diagnosing lupus rash on darker skin, compared with those on fair skin. This represents “a disparity between provider confidence and the patient population lupus traditionally affects,” the investigators concluded.

Another recent study found evidence of disparities in clinical education resources. “The lack of dark skin representation among rheumatology educational materials contributes to the implicit bias and structural racism present in medical education by promoting White-only models of disease,” lead author Adrienne Strait, a medical student at the University of California, San Francisco, said in an interview. “Given that rheumatic diseases disproportionately impact racial and ethnic minorities, we felt it was important to examine the representation of these groups within rheumatology training resources.”

She and her colleagues gathered images of rheumatic diseases from four major databases: the American College of Rheumatology’s Image Library, UpToDate, the New England Journal of Medicine Images in Clinical Medicine and Clinical Cases filtered by “Rheumatology,” and the 9th edition of Kelley’s Textbook of Rheumatology. They used Fitzpatrick’s skin phototypes to independently code images depicting skin as “light” (skin types I-IV), “dark” (skin types V-VI), or “indeterminate,” focusing on systemic lupus erythematosus (SLE) and rheumatoid arthritis, two conditions with a known connection to racial and ethnic health disparities.

Taking into account the high incidence of sarcoidosis and SLE in Black patients when compared with White patients, the investigators did a secondary analysis that excluded these cases.

Among 1,043 patient images studied, just 13.4% represented dark skin, compared with 84% that represented light skin. More than 2% represented an indeterminate skin color. Comparing dark-skin representation in the clinical images and SLE images with the representation of Asian, Native American, and Black individuals in the United States and within lupus cases nationally, the investigators found significant underrepresentation of dark skin.

Only 4.2% of RA images had dark-skin representation, making RA one of the diseases with the lowest representation in the study, along with juvenile idiopathic arthritis, the spondyloarthropathies, and Kawasaki disease. “Representation of dark skin in SLE was also lower than the proportion of Black individuals in SLE studies,” the investigators noted. Overall, representation of dark skin in SLE images was just 22.6%. Sarcoidosis comparatively had the largest representation of dark-skin images (69.6%, n = 32).

“Excluding sarcoidosis and SLE images, the overall representation of dark skin was 9.4% (n = 84), which was significantly lower than the proportion of Asian, Native American, and Black individuals within the U.S. Census population,” according to Ms. Strait and her associates. UpToDate contained the largest proportion of images of dark skin respective to other databases, whereas Kelley’s Textbook had the smallest.
 

Actionable steps

Many physicians are willing to improve upon their skills in identifying conditions on darker skin, as the study by Dr. Kannuthurai and associates suggests. Overall, 93% of the survey’s participants wanted to learn more about rashes in patients of color. “Future educational interventions may help practitioners improve their confidence when diagnosing rashes in lupus patients” with darker skin, they suggested.

Ms. Strait and her colleagues recommended a series of actionable steps to improve diversity and equity of dark skin tone representation in rheumatology curricula.

Editors of educational resources, for example, should make image diversity a priority for those diseases that are most commonly associated with cutaneous manifestations, such as SLE, vasculitis, inflammatory myopathies, systemic sclerosis, sarcoidosis, and psoriasis. They also called for educators in academic rheumatology programs to collaborate to improve diversity in resources used at the undergraduate and graduate medical education level.

Efforts should take place at the local, regional, and national level to publicly discuss and educate clinicians about rheumatic diseases in individuals of color. Speakers at rheumatology conferences should strive to educate learners about presentations of rheumatic diseases in individuals of color. The ACR in the meantime could establish a task force to enhance racial and ethnic diversity in their image library and other published resources.

“These steps may improve provider recognition and diagnosis of rheumatic disease manifestations in skin of color, which may in turn reduce health disparities among racial and ethnic minority groups,” Ms. Strait said.

Beth L. Jonas, MD, chair of the ACR’s Committee on Rheumatology Training and Workforce Issues, called the findings of this study “timely and important.” The researchers highlighted a deficiency in rheumatology training materials that needs addressing, she said in an interview. “I definitely agree that ACR needs to be mindful of this. There’s no doubt that we need to take these recommendations and move along these lines.”

The ACR took a first step in 2020 with the creation of a diversity, equity, and inclusion committee. “We are undergoing a college-wide look at what we do, with an eye toward inclusion. There is a strong interest in addressing health disparities and being an equitable and inclusive community of rheumatology health care professionals,” said Dr. Jonas, chief of the University of North Carolina at Chapel Hill’s division of rheumatology, allergy, and immunology.

The American Academy of Dermatology is also working to improve the image library with images of disease in skin of color. “Everyone’s jumping on this now,” Dr. McKinley-Grant observed. The medical profession can’t afford not to. It’s a life-threatening issue when rheumatoid arthritis and other diseases in people of color aren’t diagnosed early and correctly, she added.

Technologies seek to reduce bias

While many organizations are taking steps to improve representation of darker skin images, VisualDx has taken the lead on this, she said. “They’ve been doing this for years now. There are over 14,000 images of disease in skin of color, including all the rheumatologic diseases. There’s a mobile app and desktop decision support system, and it is very popular. A majority of medical schools have this as a library resource, and hospital systems license it for EHR integration.” Doctors can also get it individually. This enables them to share images and handouts of a diagnosis and select images of patients of color, said Dr. McKinley-Grant, who uses the VisualDx smartphone app DermExpert, which is an app for nondermatologists that features an image library of skin lesions, including darker-skin images.

ProjectIMPACT, powered by VisualDx, is another effort to support reducing health care bias in darker skin. The project is a collaboration between the New England Journal of Medicine Group and the Skin Of Color Society. According to Dr. McKinley-Grant, the organizers are building awareness of the importance of reducing the educational and clinical gaps in diagnosing patients of color and trying to get students and educators to pledge to take meaningful steps and to have real-world impact.

This isn’t just exclusive to dermatology and rheumatology – it involves all medical specialties, she stressed.

ProjectIMPACT isn’t just a resource for physicians, she continued. Librarians can also use it to develop more resources on skin of color.

The Skin Of Color Society and VisualDx have also partnered with the NEJM Group to develop a comprehensive virtual series on the impact of skin color and ethnicity on clinical research. The four-part series addresses structural racism and racial bias in medicine, hair disorders in people of color, pigmentary disorders, keloids, COVID-19 comorbidities, and cutaneous manifestations of systemic diseases in children and adults.

Nuances of recognizing disease

As a medical student, Dr. McKinley-Grant said she was fortunate to attend the Albert Schweitzer Hospital in Lambarene, Gabon, on a fellowship. For 3 months, she gained a wealth of experience examining only African patients with brown skin.

In her other training in medicine, “I’ve been at institutions with diverse populations, in Boston, New York, and Washington,” learning more about all different skin pigments.

This type of training should be more widely available, especially now, with COVID-19 producing new manifestations of skin lesions, she emphasized. Such efforts involve a diversification of images physicians are being trained on so that they can recognize the same disease in a person of color.

“Doctors have to be able to recognize different colors, different shades of brown and shades of white. Not all white skin is the same color,” she noted. In looking at a rash or lesion, “you have to learn how to discern differences in the background color of the skin, which is determined by melanin in the skin (Fitzpatrick skin types I-VI) and by what’s going on in the blood, such as how much oxygen and hemoglobin the patient has in their blood.” Inflammation and infection (erythema) will appear more violaceous in IV-VI skin types, for example.

At the University of North Carolina at Chapel Hill, a group of students and faculty have created a dermatology image library to address the deficiency in the availability of images for teaching purposes. “Our medical students recognized the gap and started this,” Dr. Jonas said. Julie Mervak, MD, assistant professor of dermatology, is spearheading this effort, with students Linnea Westerkam and Anuj Pranav Sanghvi.

“I understand that others around the country are working on similar initiatives,” Dr. Jonas said.

None of the sources for this story had any relevant disclosures.

During the first 3 months of the COVID-19 pandemic last year, about one-third of people with rheumatoid arthritis in the United States made changes in their RA medications, and, before the American College of Rheumatology tweaked its guidelines midway through that period, they were about twice as likely to make medication changes on their own than before the pandemic, according to an analysis of data in FORWARD, the National Databank for Rheumatic Diseases.

The study, published in Arthritis Care & Research, also found that about 10% of RA patients on hydroxychloroquine lost access to the drug at a time it was drawing interest as a treatment for COVID-19. Another finding was that a high percentage of patients on non–tumor necrosis factor biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase (JAK) inhibitors canceled or postponed appointments.

“Our results show that persons with RA who had medication changes in the first 3 months of the COVID-19 pandemic in the U.S. were more likely to have worse disease activity and higher exposure to prior DMARDs, but no statistical difference was found in terms of comorbidities,” first author Kaleb Michaud, PhD, and coauthors wrote. Dr. Michaud is with the National Databank for Rheumatic Diseases, Wichita, Kan., and the University of Nebraska Medical Center, Omaha.

The study evaluated responses from 734 adults who participated in FORWARD, an observational, multidisease registry. They answered online surveys about COVID-19 in May 2020 and had provided data on their medication use before the pandemic. A total of 30% (n = 221) reported medication changes in that period.
 

Details on medication changes

Medication changers were more likely to use glucocorticoids (GCs) (32.6% vs. 18.1%) and less likely to use nonhydroxychloroquine conventional DMARDs (49.3% vs. 62%) pre-COVID. Changers also reported higher rates of economic hardship during the pandemic (22.6% vs. 14.6%).

In the midst of the study period, the ACR issued a clinical guideline for treatment of rheumatic and musculoskeletal diseases (RMDs), emphasizing the need to maintain DMARD therapy, control disease activity, and reduce prednisone/GC use. The guideline advised continuing hydroxychloroquine and interleukin-6 inhibitor biologics in people with suspected or confirmed COVID-19.

Dr. Michaud and coauthors acknowledged the ongoing lack of knowledge about real-world treatment patterns for RA during the pandemic. They set out with this study to fill those knowledge gaps.

They noted that patients on bDMARDs (17.6%) and JAK inhibitors (17.1%) were more than twice as likely to discontinue medications than were those on conventional DMARDs (8.2%).

Switching to telehealth was the most common pandemic-related behavior change among patients in all DMARD groups, with rates ranging from 31% to 47.1%, followed by canceling or postponing appointments, with rates ranging from 27.9% to 36.4% depending on the DMARD group.

The study also found that RA patients widely adopted the behavior changes that the Centers for Disease Control and Prevention recommended during the pandemic, although the rates of restricting social contacts were significantly lower than the 90% reported in an early Italian study.

Dr. Michaud and coauthors also provided some explanation of why people on GCs and DMARDs were more likely than others to change medication patterns. “This may reflect efforts to reduce the perceived risk of infections due to GCs as well as the likely less-controlled disease activity associated with GC use,” they wrote. While the ACR’s early pandemic guidance followed the 2015 guidelines – that patients should continue on GCs at the “lowest possible dose” and not stop them “abruptly” – most U.S. rheumatologists reported cutting back on GC use during the pandemic.

The researchers acknowledged that evidence linking GC use with hospitalization for COVID-19, which emerged after they had surveyed study participants, was consistent their findings, but that the overall risk of COVID-19 in RA patients still isn’t known.

Pfizer funded the analysis, and a coauthor is an employee of Pfizer.

During the first 3 months of the COVID-19 pandemic last year, about one-third of people with rheumatoid arthritis in the United States made changes in their RA medications, and, before the American College of Rheumatology tweaked its guidelines midway through that period, they were about twice as likely to make medication changes on their own than before the pandemic, according to an analysis of data in FORWARD, the National Databank for Rheumatic Diseases.

The study, published in Arthritis Care & Research, also found that about 10% of RA patients on hydroxychloroquine lost access to the drug at a time it was drawing interest as a treatment for COVID-19. Another finding was that a high percentage of patients on non–tumor necrosis factor biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase (JAK) inhibitors canceled or postponed appointments.

“Our results show that persons with RA who had medication changes in the first 3 months of the COVID-19 pandemic in the U.S. were more likely to have worse disease activity and higher exposure to prior DMARDs, but no statistical difference was found in terms of comorbidities,” first author Kaleb Michaud, PhD, and coauthors wrote. Dr. Michaud is with the National Databank for Rheumatic Diseases, Wichita, Kan., and the University of Nebraska Medical Center, Omaha.

The study evaluated responses from 734 adults who participated in FORWARD, an observational, multidisease registry. They answered online surveys about COVID-19 in May 2020 and had provided data on their medication use before the pandemic. A total of 30% (n = 221) reported medication changes in that period.
 

Details on medication changes

Medication changers were more likely to use glucocorticoids (GCs) (32.6% vs. 18.1%) and less likely to use nonhydroxychloroquine conventional DMARDs (49.3% vs. 62%) pre-COVID. Changers also reported higher rates of economic hardship during the pandemic (22.6% vs. 14.6%).

In the midst of the study period, the ACR issued a clinical guideline for treatment of rheumatic and musculoskeletal diseases (RMDs), emphasizing the need to maintain DMARD therapy, control disease activity, and reduce prednisone/GC use. The guideline advised continuing hydroxychloroquine and interleukin-6 inhibitor biologics in people with suspected or confirmed COVID-19.

Dr. Michaud and coauthors acknowledged the ongoing lack of knowledge about real-world treatment patterns for RA during the pandemic. They set out with this study to fill those knowledge gaps.

They noted that patients on bDMARDs (17.6%) and JAK inhibitors (17.1%) were more than twice as likely to discontinue medications than were those on conventional DMARDs (8.2%).

Switching to telehealth was the most common pandemic-related behavior change among patients in all DMARD groups, with rates ranging from 31% to 47.1%, followed by canceling or postponing appointments, with rates ranging from 27.9% to 36.4% depending on the DMARD group.

The study also found that RA patients widely adopted the behavior changes that the Centers for Disease Control and Prevention recommended during the pandemic, although the rates of restricting social contacts were significantly lower than the 90% reported in an early Italian study.

Dr. Michaud and coauthors also provided some explanation of why people on GCs and DMARDs were more likely than others to change medication patterns. “This may reflect efforts to reduce the perceived risk of infections due to GCs as well as the likely less-controlled disease activity associated with GC use,” they wrote. While the ACR’s early pandemic guidance followed the 2015 guidelines – that patients should continue on GCs at the “lowest possible dose” and not stop them “abruptly” – most U.S. rheumatologists reported cutting back on GC use during the pandemic.

The researchers acknowledged that evidence linking GC use with hospitalization for COVID-19, which emerged after they had surveyed study participants, was consistent their findings, but that the overall risk of COVID-19 in RA patients still isn’t known.

Pfizer funded the analysis, and a coauthor is an employee of Pfizer.

During the first 3 months of the COVID-19 pandemic last year, about one-third of people with rheumatoid arthritis in the United States made changes in their RA medications, and, before the American College of Rheumatology tweaked its guidelines midway through that period, they were about twice as likely to make medication changes on their own than before the pandemic, according to an analysis of data in FORWARD, the National Databank for Rheumatic Diseases.

The study, published in Arthritis Care & Research, also found that about 10% of RA patients on hydroxychloroquine lost access to the drug at a time it was drawing interest as a treatment for COVID-19. Another finding was that a high percentage of patients on non–tumor necrosis factor biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase (JAK) inhibitors canceled or postponed appointments.

“Our results show that persons with RA who had medication changes in the first 3 months of the COVID-19 pandemic in the U.S. were more likely to have worse disease activity and higher exposure to prior DMARDs, but no statistical difference was found in terms of comorbidities,” first author Kaleb Michaud, PhD, and coauthors wrote. Dr. Michaud is with the National Databank for Rheumatic Diseases, Wichita, Kan., and the University of Nebraska Medical Center, Omaha.

The study evaluated responses from 734 adults who participated in FORWARD, an observational, multidisease registry. They answered online surveys about COVID-19 in May 2020 and had provided data on their medication use before the pandemic. A total of 30% (n = 221) reported medication changes in that period.
 

Details on medication changes

Medication changers were more likely to use glucocorticoids (GCs) (32.6% vs. 18.1%) and less likely to use nonhydroxychloroquine conventional DMARDs (49.3% vs. 62%) pre-COVID. Changers also reported higher rates of economic hardship during the pandemic (22.6% vs. 14.6%).

In the midst of the study period, the ACR issued a clinical guideline for treatment of rheumatic and musculoskeletal diseases (RMDs), emphasizing the need to maintain DMARD therapy, control disease activity, and reduce prednisone/GC use. The guideline advised continuing hydroxychloroquine and interleukin-6 inhibitor biologics in people with suspected or confirmed COVID-19.

Dr. Michaud and coauthors acknowledged the ongoing lack of knowledge about real-world treatment patterns for RA during the pandemic. They set out with this study to fill those knowledge gaps.

They noted that patients on bDMARDs (17.6%) and JAK inhibitors (17.1%) were more than twice as likely to discontinue medications than were those on conventional DMARDs (8.2%).

Switching to telehealth was the most common pandemic-related behavior change among patients in all DMARD groups, with rates ranging from 31% to 47.1%, followed by canceling or postponing appointments, with rates ranging from 27.9% to 36.4% depending on the DMARD group.

The study also found that RA patients widely adopted the behavior changes that the Centers for Disease Control and Prevention recommended during the pandemic, although the rates of restricting social contacts were significantly lower than the 90% reported in an early Italian study.

Dr. Michaud and coauthors also provided some explanation of why people on GCs and DMARDs were more likely than others to change medication patterns. “This may reflect efforts to reduce the perceived risk of infections due to GCs as well as the likely less-controlled disease activity associated with GC use,” they wrote. While the ACR’s early pandemic guidance followed the 2015 guidelines – that patients should continue on GCs at the “lowest possible dose” and not stop them “abruptly” – most U.S. rheumatologists reported cutting back on GC use during the pandemic.

The researchers acknowledged that evidence linking GC use with hospitalization for COVID-19, which emerged after they had surveyed study participants, was consistent their findings, but that the overall risk of COVID-19 in RA patients still isn’t known.

Pfizer funded the analysis, and a coauthor is an employee of Pfizer.

Although most patients with chronic inflammatory diseases mounted immune responses after two doses of mRNA-based COVID-19 vaccines, glucocorticoids and B-cell–depleting therapies markedly reduced the response, according to a recently published preprint of a new study.

Mongkolchon Akesin/Getty Images

The study, published on MedRxiv and not yet peer reviewed, involved a prospective look at 133 patients with chronic inflammatory disease (CID) and 53 patients with healthy immune systems at Washington University, St. Louis, and the University of California, San Francisco. It is regarded as the largest and most detailed study yet in how vaccines perform in people with immune-mediated inflammatory disease. The patients were enrolled between December 2020 and March 2021, and the most common diseases were inflammatory bowel disease (32%), rheumatoid arthritis (29%), spondyloarthritis (15%), and systemic lupus erythematosus (11%).
 

A ‘modest’ reduction in antibody response

Senior author Alfred Kim, MD, PhD, of the department of medicine at Washington University, said the overall results so far are encouraging.

“Most patients with an autoimmune disease that are on immunosuppression can mount antibody responses,” he said. “We’re seeing the majority of our subjects respond.”

The immune-healthy controls and most of the patients with CID had a robust immune response against the spike protein, although the CID group had a mean reduction in antibody titers that was three times lower than the controls (P = .0092). The CID group similarly had a 2.7-fold reduction in preventing neutralization, or halting the virus’ ability to infect (P < .0001), researchers reported.

This reduction in response is “modest,” he said.

“Is the level of reduction going to be detrimental for protection? Time will tell,” he said, adding that researchers anticipate that it won’t have a critical effect on protection because responses tended to be within the range of the immunocompetent controls, who themselves had wildly varied antibody titers across a 20-fold range. “ ‘Optimal’ isn’t necessarily the same as ‘sufficient.’ ”
 

Type of medication has big impact on antibody titers

But there was a wide variety of effects on the immune response depending on the medication. Glucorticoids resulted in a response that was 10 times lower than the immune-healthy controls, as well as fewer circulating plasmablasts after vaccination. Researchers found that 98% of controls were seropositive for antibody, compared with 92% of those with CID who were not taking prednisone, and 65% of CID patients on prednisone (P = .0006 and .0115, respectively). Prevention of neutralization of the virus was similarly reduced in those groups, compared with the controls. Dr. Kim noted this was a small sample size, with about 15 patients. These effects were seen regardless of the dose.

“We would’ve anticipated this would have been dose dependent, so this was a little bit surprising,” Dr. Kim said.

B-cell–depleting therapies, such as rituximab (Rituxan) and ocrelizumab (Ocrevus), reduced antibody titers by 36 times, compared with controls (P < .0001), with a similar reduction in preventing infection (P = .0066), the researchers found. The reduction in antibody titers was the most pronounced among those who had received B-cell–depleting therapies within the previous 6 months. Dr. Kim noted this was a small sample size, with about 10 patients.

CID study subjects taking an antimetabolite, including methotrexate, had an average of a two- to threefold reduction in antibody titers and in neutralization (P = .0006). This reduction was greatest with methotrexate, researchers found (P = .0027).

JAK inhibitors also significantly reduced antibody titers (P = .0066), but the reduction in neutralization of the virus was not significant. In addition, researchers found a reduction in antibody titers, the prevention of viral infection, and circulating plasmablasts among those on tumor necrosis factor (TNF) inhibitors, compared with controls, but these were insignificant statistically except for virus neutralization.

Dr. Kim said he hopes the glucocorticoid data spur physicians to try harder to wean patients off the drugs, when possible, in keeping with recommendations already in place.

“The general culture in rheumatology has been very lax about the need to reduce glucocorticoids,” he said. “This reinvigorates that call.” Questions about possible drug holidays from glucocorticoids remain, regarding how long a holiday would be needed, he said. He noted that many patients on glucocorticoids nonetheless mounted responses.

Those on B-cell–depleting therapies present a “much more difficult” question, he said. Some patients possibly could wait a bit longer than their normal, every-6-month schedule, but it’s an individual decision, he said. Since a booster of influenza vaccine has been found to enhance the response even within the 6-month window among ocrelizumab patients, a booster of COVID-19 vaccine might also help, although this remains to be studied.

The study group has already increased its sample size and is looking at adverse reactions and long-term immune responses, Dr. Kim said.

Encouraging, rather than discouraging, results

Leonard Calabrese, DO, professor of medicine at the Cleveland Clinic in Ohio, said the findings shouldn’t discourage clinicians from encouraging vaccination.

“There’s still a preponderance of people who will develop a robust antibody vaccine response,” he said.

He cautioned that the findings look only at antibodies to the spike protein and at plasmablasts. The reduction in these titers is “of concern,” he said, but “we don’t really know with certainty what are the effects of these drugs, and these data are on the overall biologic protective effect of the vaccine. There’s much more to a vaccine response than anti–spike protein and plasmablasts,” including cell-mediated immune response.

For an individual patient, the findings “mean a lot,” he said.

“I think that people who are on significant prednisone and B-cell–depleting agents, I think you have to share with them that there’s a reasonable chance that you’re not going to be making a response similar to healthy people,” he said. “Thus, even with your vaccine, we’re not going to cut you loose to do things that are violating social distancing and group settings. … Should you be hugging your grandchildren if you’re a rituximab vaccine recipient? I think I would wait until we have a little bit more data.”

Kevin Winthrop, MD, MPH, professor of ophthalmology at Oregon Health & Science University, Portland, where he studies vaccinations in the immunocompromised, said that glucocorticoids tend to have little effect on vaccinations generally at low doses.

When effects are seen they can be difficult to interpret, he said.

“It’s hard to extricate that from the effect of the underlying disease,” he said. The drug can be a proxy for worse disease control.

Although it’s a small study, it’s reassuring that overall the responses were similar to healthy controls.

For B-cell–depleting therapies, his usual guidance is to not give vaccine until a patient is at least 3 months out from their last dose, and not to restart until at least 2 weeks after vaccination.

“It’s not surprising that some of these DMARDs [disease-modifying antirheumatic drugs] do negatively affect vaccine response, particularly B-cell–depletion therapy. We need to do some studies to find a way to overcome that, or optimize delivery of the vaccine.”

Dr. Kim reported participating in consulting, advisory board, or speaker’s bureau for Alexion, Aurinia, Annexon Biosciences, Exagen Diagnostics, and GlaxoSmithKline, and receiving funding under a sponsored research agreement unrelated to the data in the paper from GlaxoSmithKline. Dr. Winthrop reported receiving consulting fees from Pfizer, AbbVie, UCB, Eli Lilly, Galapagos, GlaxoSmithKline, Roche, Gilead, Bristol-Myers Squibb, Regeneron, Sanofi, AstraZeneca, Novartis, and research grants from Bristol-Myers Squibb and Pfizer. Dr. Calabrese reported no relevant disclosures.

Although most patients with chronic inflammatory diseases mounted immune responses after two doses of mRNA-based COVID-19 vaccines, glucocorticoids and B-cell–depleting therapies markedly reduced the response, according to a recently published preprint of a new study.

Mongkolchon Akesin/Getty Images

The study, published on MedRxiv and not yet peer reviewed, involved a prospective look at 133 patients with chronic inflammatory disease (CID) and 53 patients with healthy immune systems at Washington University, St. Louis, and the University of California, San Francisco. It is regarded as the largest and most detailed study yet in how vaccines perform in people with immune-mediated inflammatory disease. The patients were enrolled between December 2020 and March 2021, and the most common diseases were inflammatory bowel disease (32%), rheumatoid arthritis (29%), spondyloarthritis (15%), and systemic lupus erythematosus (11%).
 

A ‘modest’ reduction in antibody response

Senior author Alfred Kim, MD, PhD, of the department of medicine at Washington University, said the overall results so far are encouraging.

“Most patients with an autoimmune disease that are on immunosuppression can mount antibody responses,” he said. “We’re seeing the majority of our subjects respond.”

The immune-healthy controls and most of the patients with CID had a robust immune response against the spike protein, although the CID group had a mean reduction in antibody titers that was three times lower than the controls (P = .0092). The CID group similarly had a 2.7-fold reduction in preventing neutralization, or halting the virus’ ability to infect (P < .0001), researchers reported.

This reduction in response is “modest,” he said.

“Is the level of reduction going to be detrimental for protection? Time will tell,” he said, adding that researchers anticipate that it won’t have a critical effect on protection because responses tended to be within the range of the immunocompetent controls, who themselves had wildly varied antibody titers across a 20-fold range. “ ‘Optimal’ isn’t necessarily the same as ‘sufficient.’ ”
 

Type of medication has big impact on antibody titers

But there was a wide variety of effects on the immune response depending on the medication. Glucorticoids resulted in a response that was 10 times lower than the immune-healthy controls, as well as fewer circulating plasmablasts after vaccination. Researchers found that 98% of controls were seropositive for antibody, compared with 92% of those with CID who were not taking prednisone, and 65% of CID patients on prednisone (P = .0006 and .0115, respectively). Prevention of neutralization of the virus was similarly reduced in those groups, compared with the controls. Dr. Kim noted this was a small sample size, with about 15 patients. These effects were seen regardless of the dose.

“We would’ve anticipated this would have been dose dependent, so this was a little bit surprising,” Dr. Kim said.

B-cell–depleting therapies, such as rituximab (Rituxan) and ocrelizumab (Ocrevus), reduced antibody titers by 36 times, compared with controls (P < .0001), with a similar reduction in preventing infection (P = .0066), the researchers found. The reduction in antibody titers was the most pronounced among those who had received B-cell–depleting therapies within the previous 6 months. Dr. Kim noted this was a small sample size, with about 10 patients.

CID study subjects taking an antimetabolite, including methotrexate, had an average of a two- to threefold reduction in antibody titers and in neutralization (P = .0006). This reduction was greatest with methotrexate, researchers found (P = .0027).

JAK inhibitors also significantly reduced antibody titers (P = .0066), but the reduction in neutralization of the virus was not significant. In addition, researchers found a reduction in antibody titers, the prevention of viral infection, and circulating plasmablasts among those on tumor necrosis factor (TNF) inhibitors, compared with controls, but these were insignificant statistically except for virus neutralization.

Dr. Kim said he hopes the glucocorticoid data spur physicians to try harder to wean patients off the drugs, when possible, in keeping with recommendations already in place.

“The general culture in rheumatology has been very lax about the need to reduce glucocorticoids,” he said. “This reinvigorates that call.” Questions about possible drug holidays from glucocorticoids remain, regarding how long a holiday would be needed, he said. He noted that many patients on glucocorticoids nonetheless mounted responses.

Those on B-cell–depleting therapies present a “much more difficult” question, he said. Some patients possibly could wait a bit longer than their normal, every-6-month schedule, but it’s an individual decision, he said. Since a booster of influenza vaccine has been found to enhance the response even within the 6-month window among ocrelizumab patients, a booster of COVID-19 vaccine might also help, although this remains to be studied.

The study group has already increased its sample size and is looking at adverse reactions and long-term immune responses, Dr. Kim said.

Encouraging, rather than discouraging, results

Leonard Calabrese, DO, professor of medicine at the Cleveland Clinic in Ohio, said the findings shouldn’t discourage clinicians from encouraging vaccination.

“There’s still a preponderance of people who will develop a robust antibody vaccine response,” he said.

He cautioned that the findings look only at antibodies to the spike protein and at plasmablasts. The reduction in these titers is “of concern,” he said, but “we don’t really know with certainty what are the effects of these drugs, and these data are on the overall biologic protective effect of the vaccine. There’s much more to a vaccine response than anti–spike protein and plasmablasts,” including cell-mediated immune response.

For an individual patient, the findings “mean a lot,” he said.

“I think that people who are on significant prednisone and B-cell–depleting agents, I think you have to share with them that there’s a reasonable chance that you’re not going to be making a response similar to healthy people,” he said. “Thus, even with your vaccine, we’re not going to cut you loose to do things that are violating social distancing and group settings. … Should you be hugging your grandchildren if you’re a rituximab vaccine recipient? I think I would wait until we have a little bit more data.”

Kevin Winthrop, MD, MPH, professor of ophthalmology at Oregon Health & Science University, Portland, where he studies vaccinations in the immunocompromised, said that glucocorticoids tend to have little effect on vaccinations generally at low doses.

When effects are seen they can be difficult to interpret, he said.

“It’s hard to extricate that from the effect of the underlying disease,” he said. The drug can be a proxy for worse disease control.

Although it’s a small study, it’s reassuring that overall the responses were similar to healthy controls.

For B-cell–depleting therapies, his usual guidance is to not give vaccine until a patient is at least 3 months out from their last dose, and not to restart until at least 2 weeks after vaccination.

“It’s not surprising that some of these DMARDs [disease-modifying antirheumatic drugs] do negatively affect vaccine response, particularly B-cell–depletion therapy. We need to do some studies to find a way to overcome that, or optimize delivery of the vaccine.”

Dr. Kim reported participating in consulting, advisory board, or speaker’s bureau for Alexion, Aurinia, Annexon Biosciences, Exagen Diagnostics, and GlaxoSmithKline, and receiving funding under a sponsored research agreement unrelated to the data in the paper from GlaxoSmithKline. Dr. Winthrop reported receiving consulting fees from Pfizer, AbbVie, UCB, Eli Lilly, Galapagos, GlaxoSmithKline, Roche, Gilead, Bristol-Myers Squibb, Regeneron, Sanofi, AstraZeneca, Novartis, and research grants from Bristol-Myers Squibb and Pfizer. Dr. Calabrese reported no relevant disclosures.

Although most patients with chronic inflammatory diseases mounted immune responses after two doses of mRNA-based COVID-19 vaccines, glucocorticoids and B-cell–depleting therapies markedly reduced the response, according to a recently published preprint of a new study.

Mongkolchon Akesin/Getty Images

The study, published on MedRxiv and not yet peer reviewed, involved a prospective look at 133 patients with chronic inflammatory disease (CID) and 53 patients with healthy immune systems at Washington University, St. Louis, and the University of California, San Francisco. It is regarded as the largest and most detailed study yet in how vaccines perform in people with immune-mediated inflammatory disease. The patients were enrolled between December 2020 and March 2021, and the most common diseases were inflammatory bowel disease (32%), rheumatoid arthritis (29%), spondyloarthritis (15%), and systemic lupus erythematosus (11%).
 

A ‘modest’ reduction in antibody response

Senior author Alfred Kim, MD, PhD, of the department of medicine at Washington University, said the overall results so far are encouraging.

“Most patients with an autoimmune disease that are on immunosuppression can mount antibody responses,” he said. “We’re seeing the majority of our subjects respond.”

The immune-healthy controls and most of the patients with CID had a robust immune response against the spike protein, although the CID group had a mean reduction in antibody titers that was three times lower than the controls (P = .0092). The CID group similarly had a 2.7-fold reduction in preventing neutralization, or halting the virus’ ability to infect (P < .0001), researchers reported.

This reduction in response is “modest,” he said.

“Is the level of reduction going to be detrimental for protection? Time will tell,” he said, adding that researchers anticipate that it won’t have a critical effect on protection because responses tended to be within the range of the immunocompetent controls, who themselves had wildly varied antibody titers across a 20-fold range. “ ‘Optimal’ isn’t necessarily the same as ‘sufficient.’ ”
 

Type of medication has big impact on antibody titers

But there was a wide variety of effects on the immune response depending on the medication. Glucorticoids resulted in a response that was 10 times lower than the immune-healthy controls, as well as fewer circulating plasmablasts after vaccination. Researchers found that 98% of controls were seropositive for antibody, compared with 92% of those with CID who were not taking prednisone, and 65% of CID patients on prednisone (P = .0006 and .0115, respectively). Prevention of neutralization of the virus was similarly reduced in those groups, compared with the controls. Dr. Kim noted this was a small sample size, with about 15 patients. These effects were seen regardless of the dose.

“We would’ve anticipated this would have been dose dependent, so this was a little bit surprising,” Dr. Kim said.

B-cell–depleting therapies, such as rituximab (Rituxan) and ocrelizumab (Ocrevus), reduced antibody titers by 36 times, compared with controls (P < .0001), with a similar reduction in preventing infection (P = .0066), the researchers found. The reduction in antibody titers was the most pronounced among those who had received B-cell–depleting therapies within the previous 6 months. Dr. Kim noted this was a small sample size, with about 10 patients.

CID study subjects taking an antimetabolite, including methotrexate, had an average of a two- to threefold reduction in antibody titers and in neutralization (P = .0006). This reduction was greatest with methotrexate, researchers found (P = .0027).

JAK inhibitors also significantly reduced antibody titers (P = .0066), but the reduction in neutralization of the virus was not significant. In addition, researchers found a reduction in antibody titers, the prevention of viral infection, and circulating plasmablasts among those on tumor necrosis factor (TNF) inhibitors, compared with controls, but these were insignificant statistically except for virus neutralization.

Dr. Kim said he hopes the glucocorticoid data spur physicians to try harder to wean patients off the drugs, when possible, in keeping with recommendations already in place.

“The general culture in rheumatology has been very lax about the need to reduce glucocorticoids,” he said. “This reinvigorates that call.” Questions about possible drug holidays from glucocorticoids remain, regarding how long a holiday would be needed, he said. He noted that many patients on glucocorticoids nonetheless mounted responses.

Those on B-cell–depleting therapies present a “much more difficult” question, he said. Some patients possibly could wait a bit longer than their normal, every-6-month schedule, but it’s an individual decision, he said. Since a booster of influenza vaccine has been found to enhance the response even within the 6-month window among ocrelizumab patients, a booster of COVID-19 vaccine might also help, although this remains to be studied.

The study group has already increased its sample size and is looking at adverse reactions and long-term immune responses, Dr. Kim said.

Encouraging, rather than discouraging, results

Leonard Calabrese, DO, professor of medicine at the Cleveland Clinic in Ohio, said the findings shouldn’t discourage clinicians from encouraging vaccination.

“There’s still a preponderance of people who will develop a robust antibody vaccine response,” he said.

He cautioned that the findings look only at antibodies to the spike protein and at plasmablasts. The reduction in these titers is “of concern,” he said, but “we don’t really know with certainty what are the effects of these drugs, and these data are on the overall biologic protective effect of the vaccine. There’s much more to a vaccine response than anti–spike protein and plasmablasts,” including cell-mediated immune response.

For an individual patient, the findings “mean a lot,” he said.

“I think that people who are on significant prednisone and B-cell–depleting agents, I think you have to share with them that there’s a reasonable chance that you’re not going to be making a response similar to healthy people,” he said. “Thus, even with your vaccine, we’re not going to cut you loose to do things that are violating social distancing and group settings. … Should you be hugging your grandchildren if you’re a rituximab vaccine recipient? I think I would wait until we have a little bit more data.”

Kevin Winthrop, MD, MPH, professor of ophthalmology at Oregon Health & Science University, Portland, where he studies vaccinations in the immunocompromised, said that glucocorticoids tend to have little effect on vaccinations generally at low doses.

When effects are seen they can be difficult to interpret, he said.

“It’s hard to extricate that from the effect of the underlying disease,” he said. The drug can be a proxy for worse disease control.

Although it’s a small study, it’s reassuring that overall the responses were similar to healthy controls.

For B-cell–depleting therapies, his usual guidance is to not give vaccine until a patient is at least 3 months out from their last dose, and not to restart until at least 2 weeks after vaccination.

“It’s not surprising that some of these DMARDs [disease-modifying antirheumatic drugs] do negatively affect vaccine response, particularly B-cell–depletion therapy. We need to do some studies to find a way to overcome that, or optimize delivery of the vaccine.”

Dr. Kim reported participating in consulting, advisory board, or speaker’s bureau for Alexion, Aurinia, Annexon Biosciences, Exagen Diagnostics, and GlaxoSmithKline, and receiving funding under a sponsored research agreement unrelated to the data in the paper from GlaxoSmithKline. Dr. Winthrop reported receiving consulting fees from Pfizer, AbbVie, UCB, Eli Lilly, Galapagos, GlaxoSmithKline, Roche, Gilead, Bristol-Myers Squibb, Regeneron, Sanofi, AstraZeneca, Novartis, and research grants from Bristol-Myers Squibb and Pfizer. Dr. Calabrese reported no relevant disclosures.

Adults with knee osteoarthritis (OA) who participated in a self-directed, web-based exercise program with automated text-message reminders and encouragement for 6 months showed significant improvement in overall knee pain and physical function, compared with patients who received web-based OA information alone, in a randomized trial of 180 individuals.

copyright Nandyphotos/Thinkstock

The results support a role for web-based exercise intervention to improve knee OA patients’ access to recommended exercises and to assist clinicians in managing patients on a population level, according to the first author of the study, Rachel Kate Nelligan, of the University of Melbourne, and colleagues. Their report is in JAMA Internal Medicine.

“Our free-to-access, unsupervised program could serve as an entry-level intervention, with participants who do not experience clinical benefits progressing to subsequent steps for more intensive, personalized management,” they said. “Such an approach has the potential to better distribute limited health care resources and reduce demand for contact with health professionals, thus improving access for those requiring it.”

Only two other randomized, clinical trials have evaluated web-based interventions for OA without contact from health professionals, according to the authors. While one of those did not find any differences in outcomes at 4 months when comparing a self-directed progressive lower-limb strength, flexibility, and walking program to being on a wait list, a separate trial evaluating a 9-module physical activity program in adults with knee and/or hip OA vs. a wait-list control group found evidence for efficacy for physical function at 3 months, but not quality of life or function in sport and recreation.

For the current study, researchers recruited 206 adults in Australia with clinically diagnosed knee OA via online advertisements and a volunteer database. Participants were aged 45 years or older, and reported activity-related knee pain and morning knee stiffness lasting at least 30 minutes; knee pain on most days for at least 3 months; and average knee pain severity of 4 or higher on an 11-point numeric rating scale in the previous week. In addition, participants were required to own a cell phone with text messaging, have Internet access, and be able to complete assessments.

Patients randomized to the intervention of the My Knee Exercise website received web-based information about OA and the value of exercise, with a 24-week self-directed program of strengthening exercises plus automated text messages to motivate behavior changes and encourage adherence to the exercise program. Controls received access to web-based information about OA and the value of exercise, but without the prescribed exercises or texts. Patients in the intervention group received an average of 60 text messages during the study period, and the average reply rate was 73%.

The primary study outcomes were changes in overall knee pain based on a numeric 0-10 rating scale and changes in physical function based on the Western Ontario and McMaster Universities Osteoarthritis Index 0-68 scale. A total of 180 participants completed both primary outcome measures at 24 weeks. The average age of the participants was 60 years, and 61% were women.

After 24 weeks, the intervention group averaged significantly greater improvement of 1.6 units for overall knee pain (P < .001) and 5.2 units for physical function (P = .002), compared with controls.

In addition, the proportion of patients who exceeded the minimal clinically important difference in pain improvement of at least 1.8 units was significantly higher in the intervention group, compared with controls (72.1% vs. 42.0%; P < .001). Similarly, more intervention-group patients achieved the minimal clinically important difference in WOMAC physical function of improvement of at least 6 units (68.0% vs. 40.8%; P < .001).

Secondary outcomes included additional measures of knee pain, knee function for sport and recreation, quality of life, physical activity, self-efficacy, overall improvement, and treatment satisfaction. Between-group differences favored the intervention on most measures, including Knee Injury and Osteoarthritis Outcome Score subscales for pain, sports/recreation, and quality of life; health-related quality of life; Arthritis Self-Efficacy Scale (ASES) pain subscale, individual change since baseline, and overall patient satisfaction. “Changes in PASE [Physical Activity Scale for the Elderly], ASES function, and SEE [Self Efficacy Exercise] were similar in both groups,” the researchers said.

No serious adverse events were reported by any study participants. Eight patients in the intervention group reported knee pain during the study, compared with one of the controls, and use of pain medications was similar between the groups, except that more control participants used massage, heat or cold, and topical anti-inflammatories.

The results suggest that a majority of participants in the intervention group improved pain and function without the need for in-person contact with a health professional, the researchers noted. However, more intensive management may be needed to support the 30% who did not benefit from the unsupervised approach, they said.

The study findings were limited by several factors, including the potential bias of a volunteer study population, possible lack of generalizability to individuals with lower levels of education or self-efficacy, and lack of direct comparison between web-based intervention and clinician-delivered intervention, the researchers noted.

The study was funded by the National Health and Medical Research Council, whose fellowships supported two of the authors. Lead author Ms. Nelligan disclosed a PhD scholarship from the Australian Government Research Training Program and personal fees from the University of Melbourne unrelated to the current study.

Adults with knee osteoarthritis (OA) who participated in a self-directed, web-based exercise program with automated text-message reminders and encouragement for 6 months showed significant improvement in overall knee pain and physical function, compared with patients who received web-based OA information alone, in a randomized trial of 180 individuals.

copyright Nandyphotos/Thinkstock

The results support a role for web-based exercise intervention to improve knee OA patients’ access to recommended exercises and to assist clinicians in managing patients on a population level, according to the first author of the study, Rachel Kate Nelligan, of the University of Melbourne, and colleagues. Their report is in JAMA Internal Medicine.

“Our free-to-access, unsupervised program could serve as an entry-level intervention, with participants who do not experience clinical benefits progressing to subsequent steps for more intensive, personalized management,” they said. “Such an approach has the potential to better distribute limited health care resources and reduce demand for contact with health professionals, thus improving access for those requiring it.”

Only two other randomized, clinical trials have evaluated web-based interventions for OA without contact from health professionals, according to the authors. While one of those did not find any differences in outcomes at 4 months when comparing a self-directed progressive lower-limb strength, flexibility, and walking program to being on a wait list, a separate trial evaluating a 9-module physical activity program in adults with knee and/or hip OA vs. a wait-list control group found evidence for efficacy for physical function at 3 months, but not quality of life or function in sport and recreation.

For the current study, researchers recruited 206 adults in Australia with clinically diagnosed knee OA via online advertisements and a volunteer database. Participants were aged 45 years or older, and reported activity-related knee pain and morning knee stiffness lasting at least 30 minutes; knee pain on most days for at least 3 months; and average knee pain severity of 4 or higher on an 11-point numeric rating scale in the previous week. In addition, participants were required to own a cell phone with text messaging, have Internet access, and be able to complete assessments.

Patients randomized to the intervention of the My Knee Exercise website received web-based information about OA and the value of exercise, with a 24-week self-directed program of strengthening exercises plus automated text messages to motivate behavior changes and encourage adherence to the exercise program. Controls received access to web-based information about OA and the value of exercise, but without the prescribed exercises or texts. Patients in the intervention group received an average of 60 text messages during the study period, and the average reply rate was 73%.

The primary study outcomes were changes in overall knee pain based on a numeric 0-10 rating scale and changes in physical function based on the Western Ontario and McMaster Universities Osteoarthritis Index 0-68 scale. A total of 180 participants completed both primary outcome measures at 24 weeks. The average age of the participants was 60 years, and 61% were women.

After 24 weeks, the intervention group averaged significantly greater improvement of 1.6 units for overall knee pain (P < .001) and 5.2 units for physical function (P = .002), compared with controls.

In addition, the proportion of patients who exceeded the minimal clinically important difference in pain improvement of at least 1.8 units was significantly higher in the intervention group, compared with controls (72.1% vs. 42.0%; P < .001). Similarly, more intervention-group patients achieved the minimal clinically important difference in WOMAC physical function of improvement of at least 6 units (68.0% vs. 40.8%; P < .001).

Secondary outcomes included additional measures of knee pain, knee function for sport and recreation, quality of life, physical activity, self-efficacy, overall improvement, and treatment satisfaction. Between-group differences favored the intervention on most measures, including Knee Injury and Osteoarthritis Outcome Score subscales for pain, sports/recreation, and quality of life; health-related quality of life; Arthritis Self-Efficacy Scale (ASES) pain subscale, individual change since baseline, and overall patient satisfaction. “Changes in PASE [Physical Activity Scale for the Elderly], ASES function, and SEE [Self Efficacy Exercise] were similar in both groups,” the researchers said.

No serious adverse events were reported by any study participants. Eight patients in the intervention group reported knee pain during the study, compared with one of the controls, and use of pain medications was similar between the groups, except that more control participants used massage, heat or cold, and topical anti-inflammatories.

The results suggest that a majority of participants in the intervention group improved pain and function without the need for in-person contact with a health professional, the researchers noted. However, more intensive management may be needed to support the 30% who did not benefit from the unsupervised approach, they said.

The study findings were limited by several factors, including the potential bias of a volunteer study population, possible lack of generalizability to individuals with lower levels of education or self-efficacy, and lack of direct comparison between web-based intervention and clinician-delivered intervention, the researchers noted.

The study was funded by the National Health and Medical Research Council, whose fellowships supported two of the authors. Lead author Ms. Nelligan disclosed a PhD scholarship from the Australian Government Research Training Program and personal fees from the University of Melbourne unrelated to the current study.

Adults with knee osteoarthritis (OA) who participated in a self-directed, web-based exercise program with automated text-message reminders and encouragement for 6 months showed significant improvement in overall knee pain and physical function, compared with patients who received web-based OA information alone, in a randomized trial of 180 individuals.

copyright Nandyphotos/Thinkstock

The results support a role for web-based exercise intervention to improve knee OA patients’ access to recommended exercises and to assist clinicians in managing patients on a population level, according to the first author of the study, Rachel Kate Nelligan, of the University of Melbourne, and colleagues. Their report is in JAMA Internal Medicine.

“Our free-to-access, unsupervised program could serve as an entry-level intervention, with participants who do not experience clinical benefits progressing to subsequent steps for more intensive, personalized management,” they said. “Such an approach has the potential to better distribute limited health care resources and reduce demand for contact with health professionals, thus improving access for those requiring it.”

Only two other randomized, clinical trials have evaluated web-based interventions for OA without contact from health professionals, according to the authors. While one of those did not find any differences in outcomes at 4 months when comparing a self-directed progressive lower-limb strength, flexibility, and walking program to being on a wait list, a separate trial evaluating a 9-module physical activity program in adults with knee and/or hip OA vs. a wait-list control group found evidence for efficacy for physical function at 3 months, but not quality of life or function in sport and recreation.

For the current study, researchers recruited 206 adults in Australia with clinically diagnosed knee OA via online advertisements and a volunteer database. Participants were aged 45 years or older, and reported activity-related knee pain and morning knee stiffness lasting at least 30 minutes; knee pain on most days for at least 3 months; and average knee pain severity of 4 or higher on an 11-point numeric rating scale in the previous week. In addition, participants were required to own a cell phone with text messaging, have Internet access, and be able to complete assessments.

Patients randomized to the intervention of the My Knee Exercise website received web-based information about OA and the value of exercise, with a 24-week self-directed program of strengthening exercises plus automated text messages to motivate behavior changes and encourage adherence to the exercise program. Controls received access to web-based information about OA and the value of exercise, but without the prescribed exercises or texts. Patients in the intervention group received an average of 60 text messages during the study period, and the average reply rate was 73%.

The primary study outcomes were changes in overall knee pain based on a numeric 0-10 rating scale and changes in physical function based on the Western Ontario and McMaster Universities Osteoarthritis Index 0-68 scale. A total of 180 participants completed both primary outcome measures at 24 weeks. The average age of the participants was 60 years, and 61% were women.

After 24 weeks, the intervention group averaged significantly greater improvement of 1.6 units for overall knee pain (P < .001) and 5.2 units for physical function (P = .002), compared with controls.

In addition, the proportion of patients who exceeded the minimal clinically important difference in pain improvement of at least 1.8 units was significantly higher in the intervention group, compared with controls (72.1% vs. 42.0%; P < .001). Similarly, more intervention-group patients achieved the minimal clinically important difference in WOMAC physical function of improvement of at least 6 units (68.0% vs. 40.8%; P < .001).

Secondary outcomes included additional measures of knee pain, knee function for sport and recreation, quality of life, physical activity, self-efficacy, overall improvement, and treatment satisfaction. Between-group differences favored the intervention on most measures, including Knee Injury and Osteoarthritis Outcome Score subscales for pain, sports/recreation, and quality of life; health-related quality of life; Arthritis Self-Efficacy Scale (ASES) pain subscale, individual change since baseline, and overall patient satisfaction. “Changes in PASE [Physical Activity Scale for the Elderly], ASES function, and SEE [Self Efficacy Exercise] were similar in both groups,” the researchers said.

No serious adverse events were reported by any study participants. Eight patients in the intervention group reported knee pain during the study, compared with one of the controls, and use of pain medications was similar between the groups, except that more control participants used massage, heat or cold, and topical anti-inflammatories.

The results suggest that a majority of participants in the intervention group improved pain and function without the need for in-person contact with a health professional, the researchers noted. However, more intensive management may be needed to support the 30% who did not benefit from the unsupervised approach, they said.

The study findings were limited by several factors, including the potential bias of a volunteer study population, possible lack of generalizability to individuals with lower levels of education or self-efficacy, and lack of direct comparison between web-based intervention and clinician-delivered intervention, the researchers noted.

The study was funded by the National Health and Medical Research Council, whose fellowships supported two of the authors. Lead author Ms. Nelligan disclosed a PhD scholarship from the Australian Government Research Training Program and personal fees from the University of Melbourne unrelated to the current study.