Lupus & Connective Tissue Diseases

PHILADELPHIA – Combining the immunomodulatory agent mycophenolate with the antifibrotic pirfenidone led to more rapid improvement and showed a trend to be more effective than mycophenolate mofetil alone for treating the signs and symptoms of scleroderma-related interstitial lung disease, but the combination therapy came with an increase in side effects, according to results from the Scleroderma Lung Study III.

Dinesh Khanna, MBBS, MSc, of the University of Michigan, Ann Arbor, presented the results at the annual meeting of the American College of Rheumatology. He noted some problems with the study – namely its small size, enrolling only 51 patients, about one-third of its original goal. But he also said it showed a potential signal for efficacy and that the study itself could serve as a “template” for future studies of combination mycophenolate mofetil (MMF) plus pirfenidone therapy for scleroderma-related interstitial lung disease (SSc-ILD).

“The pirfenidone patients had quite a bit more GI side effects and photosensitivity, and those are known side effects,” Dr. Khanna said in an interview. “So the combination therapy had more side effects but trends to higher efficacy.”

The design of SLS-III, a phase 2 clinical trial, was a challenge, Dr. Khanna explained. The goal was to enroll 150 SSc-ILD patients who hadn’t had any previous treatment for their disease. Finding those patients proved difficult. “In fact, if you look at the recent history, 70% of the patients with early diffuse scleroderma are on MMF,” he said in his presentation. Compounding low study enrollment was the intervening COVID-19 pandemic, he added.
 

Testing a faster-acting combination

Nonetheless, the trial managed to enroll 27 patients in the combination therapy group and 24 in the MMF-plus-placebo group and compared their outcomes over 18 months. Study dosing was 1,500 mg MMF twice daily and pirfenidone 801 mg three times daily, titrated to the tolerable dose.

Despite the study’s being underpowered, Dr. Khanna said, it still reported some notable outcomes that merit further investigation. “I think what was intriguing in the study was the long-term benefit in the patient-reported outcomes and the structural changes,” he said in the interview.

Among those notable outcomes was a clinically significant change in forced vital capacity (FVC) percentage for the combination vs. the placebo groups: 2.24% vs. 2.09%. He also noted that the combination group saw a somewhat more robust improvement in FVC at six months: 2.59% (± 0.98%) vs. 0.92% (± 1.1%) in the placebo group.

The combination group showed greater improvements in high-resolution computed tomography-evaluated lung involvement and lung fibrosis and patient-reported outcomes, including a statistically significant 3.67-point greater improvement in PROMIS-29 physical function score (4.42 vs. 0.75).

The patients on combination therapy had higher rates of serious adverse events (SAEs), and seven discontinued one or both study drugs early, all in the combined arm. Four combination therapy patients had six SAEs, compared to two placebo patients with three SAEs. In the combination group, SAEs included chest pain, herpes zoster ophthalmicus, nodular basal cell cancer, marginal zone B cell lymphoma, renal crisis, and dyspnea. SAEs in the placebo group were colitis, COVID-19 and hypoxic respiratory failure.

Study design challenges

Nonetheless, Dr. Khanna said the SLS-III data are consistent with the SLS-II findings, with mean improvements in FVC of 2.24% and 2.1%, respectively.

“The next study may be able to replicate what we tried to do, keeping in mind that there are really no MMF-naive patients who are walking around,” Dr. Khanna said. “So the challenge is about the feasibility of recruiting within a trial vs. trying to show a statistical difference between the drug and placebo.”

This study could serve as a foundation for future studies of MMF in patients with SSc-ILD, Robert Spiera, MD, of the Hospital for Special Surgery in New York, said in an interview. “There are lessons to be learned both from the study but also from prior studies looking at MMF use in the background in patients treated with other drugs in clinical trials,” he said.

Dr. Spiera noted that the study had other challenges besides the difficulty in recruiting patients who hadn’t been on MMF therapy. “A great challenge is that the benefit with regard to the impact on the lungs from MMF seems most prominent in the first 6 months to a year to even 2 years that somebody is on the drug,” he said.

The other challenge with this study is that a large proportion of patients had limited systemic disease and relatively lower levels of skin disease compared with other studies of patients on MMF, Dr. Spiera said.

“The optimal treatment of scleroderma-associated lung disease remains a very important and not-adequately met need,” he said. “Particularly, we’re looking for drugs that are tolerable in a patient population that are very prone to GI side effects in general. This study and others have taught us a lot about trial design, and I think more globally this will allow us to move this field forward.”

Dr. Khanna disclosed relationships with Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Horizon Therapeutics USA, Janssen Global Services, Prometheus Biosciences, Mitsubishi Tanabe Pharma Corp., Genentech/Roche, Theraly, and Pfizer. Genentech provided funding for the study and pirfenidone and placebo drugs at no cost.

Dr. Spiera disclosed relationships with GlaxoSmithKline, Boehringer-Ingelheim, Corbus Pharmaceutical, InflaRx, AbbVie/Abbott, Sanofi, Novartis, Chemocentryx, Roche and Vera.

PHILADELPHIA – Combining the immunomodulatory agent mycophenolate with the antifibrotic pirfenidone led to more rapid improvement and showed a trend to be more effective than mycophenolate mofetil alone for treating the signs and symptoms of scleroderma-related interstitial lung disease, but the combination therapy came with an increase in side effects, according to results from the Scleroderma Lung Study III.

Dinesh Khanna, MBBS, MSc, of the University of Michigan, Ann Arbor, presented the results at the annual meeting of the American College of Rheumatology. He noted some problems with the study – namely its small size, enrolling only 51 patients, about one-third of its original goal. But he also said it showed a potential signal for efficacy and that the study itself could serve as a “template” for future studies of combination mycophenolate mofetil (MMF) plus pirfenidone therapy for scleroderma-related interstitial lung disease (SSc-ILD).

“The pirfenidone patients had quite a bit more GI side effects and photosensitivity, and those are known side effects,” Dr. Khanna said in an interview. “So the combination therapy had more side effects but trends to higher efficacy.”

The design of SLS-III, a phase 2 clinical trial, was a challenge, Dr. Khanna explained. The goal was to enroll 150 SSc-ILD patients who hadn’t had any previous treatment for their disease. Finding those patients proved difficult. “In fact, if you look at the recent history, 70% of the patients with early diffuse scleroderma are on MMF,” he said in his presentation. Compounding low study enrollment was the intervening COVID-19 pandemic, he added.
 

Testing a faster-acting combination

Nonetheless, the trial managed to enroll 27 patients in the combination therapy group and 24 in the MMF-plus-placebo group and compared their outcomes over 18 months. Study dosing was 1,500 mg MMF twice daily and pirfenidone 801 mg three times daily, titrated to the tolerable dose.

Despite the study’s being underpowered, Dr. Khanna said, it still reported some notable outcomes that merit further investigation. “I think what was intriguing in the study was the long-term benefit in the patient-reported outcomes and the structural changes,” he said in the interview.

Among those notable outcomes was a clinically significant change in forced vital capacity (FVC) percentage for the combination vs. the placebo groups: 2.24% vs. 2.09%. He also noted that the combination group saw a somewhat more robust improvement in FVC at six months: 2.59% (± 0.98%) vs. 0.92% (± 1.1%) in the placebo group.

The combination group showed greater improvements in high-resolution computed tomography-evaluated lung involvement and lung fibrosis and patient-reported outcomes, including a statistically significant 3.67-point greater improvement in PROMIS-29 physical function score (4.42 vs. 0.75).

The patients on combination therapy had higher rates of serious adverse events (SAEs), and seven discontinued one or both study drugs early, all in the combined arm. Four combination therapy patients had six SAEs, compared to two placebo patients with three SAEs. In the combination group, SAEs included chest pain, herpes zoster ophthalmicus, nodular basal cell cancer, marginal zone B cell lymphoma, renal crisis, and dyspnea. SAEs in the placebo group were colitis, COVID-19 and hypoxic respiratory failure.

Study design challenges

Nonetheless, Dr. Khanna said the SLS-III data are consistent with the SLS-II findings, with mean improvements in FVC of 2.24% and 2.1%, respectively.

“The next study may be able to replicate what we tried to do, keeping in mind that there are really no MMF-naive patients who are walking around,” Dr. Khanna said. “So the challenge is about the feasibility of recruiting within a trial vs. trying to show a statistical difference between the drug and placebo.”

This study could serve as a foundation for future studies of MMF in patients with SSc-ILD, Robert Spiera, MD, of the Hospital for Special Surgery in New York, said in an interview. “There are lessons to be learned both from the study but also from prior studies looking at MMF use in the background in patients treated with other drugs in clinical trials,” he said.

Dr. Spiera noted that the study had other challenges besides the difficulty in recruiting patients who hadn’t been on MMF therapy. “A great challenge is that the benefit with regard to the impact on the lungs from MMF seems most prominent in the first 6 months to a year to even 2 years that somebody is on the drug,” he said.

The other challenge with this study is that a large proportion of patients had limited systemic disease and relatively lower levels of skin disease compared with other studies of patients on MMF, Dr. Spiera said.

“The optimal treatment of scleroderma-associated lung disease remains a very important and not-adequately met need,” he said. “Particularly, we’re looking for drugs that are tolerable in a patient population that are very prone to GI side effects in general. This study and others have taught us a lot about trial design, and I think more globally this will allow us to move this field forward.”

Dr. Khanna disclosed relationships with Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Horizon Therapeutics USA, Janssen Global Services, Prometheus Biosciences, Mitsubishi Tanabe Pharma Corp., Genentech/Roche, Theraly, and Pfizer. Genentech provided funding for the study and pirfenidone and placebo drugs at no cost.

Dr. Spiera disclosed relationships with GlaxoSmithKline, Boehringer-Ingelheim, Corbus Pharmaceutical, InflaRx, AbbVie/Abbott, Sanofi, Novartis, Chemocentryx, Roche and Vera.

PHILADELPHIA – Combining the immunomodulatory agent mycophenolate with the antifibrotic pirfenidone led to more rapid improvement and showed a trend to be more effective than mycophenolate mofetil alone for treating the signs and symptoms of scleroderma-related interstitial lung disease, but the combination therapy came with an increase in side effects, according to results from the Scleroderma Lung Study III.

Dinesh Khanna, MBBS, MSc, of the University of Michigan, Ann Arbor, presented the results at the annual meeting of the American College of Rheumatology. He noted some problems with the study – namely its small size, enrolling only 51 patients, about one-third of its original goal. But he also said it showed a potential signal for efficacy and that the study itself could serve as a “template” for future studies of combination mycophenolate mofetil (MMF) plus pirfenidone therapy for scleroderma-related interstitial lung disease (SSc-ILD).

“The pirfenidone patients had quite a bit more GI side effects and photosensitivity, and those are known side effects,” Dr. Khanna said in an interview. “So the combination therapy had more side effects but trends to higher efficacy.”

The design of SLS-III, a phase 2 clinical trial, was a challenge, Dr. Khanna explained. The goal was to enroll 150 SSc-ILD patients who hadn’t had any previous treatment for their disease. Finding those patients proved difficult. “In fact, if you look at the recent history, 70% of the patients with early diffuse scleroderma are on MMF,” he said in his presentation. Compounding low study enrollment was the intervening COVID-19 pandemic, he added.
 

Testing a faster-acting combination

Nonetheless, the trial managed to enroll 27 patients in the combination therapy group and 24 in the MMF-plus-placebo group and compared their outcomes over 18 months. Study dosing was 1,500 mg MMF twice daily and pirfenidone 801 mg three times daily, titrated to the tolerable dose.

Despite the study’s being underpowered, Dr. Khanna said, it still reported some notable outcomes that merit further investigation. “I think what was intriguing in the study was the long-term benefit in the patient-reported outcomes and the structural changes,” he said in the interview.

Among those notable outcomes was a clinically significant change in forced vital capacity (FVC) percentage for the combination vs. the placebo groups: 2.24% vs. 2.09%. He also noted that the combination group saw a somewhat more robust improvement in FVC at six months: 2.59% (± 0.98%) vs. 0.92% (± 1.1%) in the placebo group.

The combination group showed greater improvements in high-resolution computed tomography-evaluated lung involvement and lung fibrosis and patient-reported outcomes, including a statistically significant 3.67-point greater improvement in PROMIS-29 physical function score (4.42 vs. 0.75).

The patients on combination therapy had higher rates of serious adverse events (SAEs), and seven discontinued one or both study drugs early, all in the combined arm. Four combination therapy patients had six SAEs, compared to two placebo patients with three SAEs. In the combination group, SAEs included chest pain, herpes zoster ophthalmicus, nodular basal cell cancer, marginal zone B cell lymphoma, renal crisis, and dyspnea. SAEs in the placebo group were colitis, COVID-19 and hypoxic respiratory failure.

Study design challenges

Nonetheless, Dr. Khanna said the SLS-III data are consistent with the SLS-II findings, with mean improvements in FVC of 2.24% and 2.1%, respectively.

“The next study may be able to replicate what we tried to do, keeping in mind that there are really no MMF-naive patients who are walking around,” Dr. Khanna said. “So the challenge is about the feasibility of recruiting within a trial vs. trying to show a statistical difference between the drug and placebo.”

This study could serve as a foundation for future studies of MMF in patients with SSc-ILD, Robert Spiera, MD, of the Hospital for Special Surgery in New York, said in an interview. “There are lessons to be learned both from the study but also from prior studies looking at MMF use in the background in patients treated with other drugs in clinical trials,” he said.

Dr. Spiera noted that the study had other challenges besides the difficulty in recruiting patients who hadn’t been on MMF therapy. “A great challenge is that the benefit with regard to the impact on the lungs from MMF seems most prominent in the first 6 months to a year to even 2 years that somebody is on the drug,” he said.

The other challenge with this study is that a large proportion of patients had limited systemic disease and relatively lower levels of skin disease compared with other studies of patients on MMF, Dr. Spiera said.

“The optimal treatment of scleroderma-associated lung disease remains a very important and not-adequately met need,” he said. “Particularly, we’re looking for drugs that are tolerable in a patient population that are very prone to GI side effects in general. This study and others have taught us a lot about trial design, and I think more globally this will allow us to move this field forward.”

Dr. Khanna disclosed relationships with Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Horizon Therapeutics USA, Janssen Global Services, Prometheus Biosciences, Mitsubishi Tanabe Pharma Corp., Genentech/Roche, Theraly, and Pfizer. Genentech provided funding for the study and pirfenidone and placebo drugs at no cost.

Dr. Spiera disclosed relationships with GlaxoSmithKline, Boehringer-Ingelheim, Corbus Pharmaceutical, InflaRx, AbbVie/Abbott, Sanofi, Novartis, Chemocentryx, Roche and Vera.

PHILADELPHIA – Patients with systemic lupus erythematosus treated with lower doses of hydroxychloroquine (HCQ) had an increased risk for hospitalization for flares, according to study results presented during a press conference at the annual meeting of the American College of Rheumatology.

Doses decreased with changing guidelines

Guidelines over the years have recommended decreasing doses of HCQ. In 2011, ophthalmology guidelines recommended limiting HCQ dosing to 6.5 mg/kg per day or less of ideal body weight to reduce the chance of retinopathy. For many patients, this required a dose lower than 400 mg/day, an amount frequently used to treat lupus.

In 2016, updated guidelines further lowered the dosage of HCQ, recommending 5 mg/kg or less of patient’s actual body weight.

The effects that lower dosing has had on SLE-associated hospitalizations was unknown, which inspired Dr. Nestor’s research.

The team conducted a case-crossover study within the Mass General Brigham SLE cohort.

Hospitalizations studied over a decade

Dr. Nestor and colleagues identified patients with SLE (via electronic health records) who had at least one visit for SLE and were prescribed HCQ between January 2011 and December 2021, the period over which the recommendations were made.

They identified patients who had been hospitalized during that decade with SLE as the primary discharge diagnosis.

Patients were excluded if they had non-SLE indications, such as kidney transplant or infection without a concomitant SLE flare.

Of 2,971 patients with SLE who used HCQ, 576 had at least one hospitalization with primary discharge diagnosis of SLE.

Of these, 108 were hospitalized for an SLE flare and had used HCQ prior to that hospitalization and had at least one control period with HCQ use during the study period.

All of the patients in the study had to have a case period and a control period, Dr. Nestor explained. The case period was 6 months on HCQ ending in hospitalization for lupus and the control period was 6 months on HCQ that did not end in hospitalization for lupus.
 

Significantly increased hospitalizations

Low-dose HCQ by weight-based dose (≤ 5 vs. > 5 mg/kg per day) and by non–weight-based dose (< 400 vs. 400 mg per day) were both associated with significantly increased hospitalizations for SLE (adjusted odds ratio, 4.41; 95% confidence interval, 1.50-12.98; and AOR, 3.48; 95% CI, 1.33-9.13, respectively).

The average age of the hospitalized group was 36 years. Most patients (92%) were female, 43.5% were White, and 32.4% were Black.

In calling for reassessment of the dosing, Dr. Nestor said, “We are protecting our patients against a very long-term side effect of hydroxychloroquine retinopathy. [It] typically takes 10-20 years to develop in our patients. But by doing that, we’re missing many of the short-term benefits from hydroxychloroquine in our patients, leading to more lupus flares, which leads to more end-organ damage.”

She said patients taking HCQ for lupus are asked to see an ophthalmologist once a year to monitor for the side effect, adding that rheumatologists and ophthalmologists could work together to adjust the guidelines.

Dr. Nestor suggested it’s possible that patients need higher doses of HCQ earlier in their disease and lower doses later. “Perhaps it’s just the patients who are particularly active who need the higher doses,” she said.

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

PHILADELPHIA – Patients with systemic lupus erythematosus treated with lower doses of hydroxychloroquine (HCQ) had an increased risk for hospitalization for flares, according to study results presented during a press conference at the annual meeting of the American College of Rheumatology.

Doses decreased with changing guidelines

Guidelines over the years have recommended decreasing doses of HCQ. In 2011, ophthalmology guidelines recommended limiting HCQ dosing to 6.5 mg/kg per day or less of ideal body weight to reduce the chance of retinopathy. For many patients, this required a dose lower than 400 mg/day, an amount frequently used to treat lupus.

In 2016, updated guidelines further lowered the dosage of HCQ, recommending 5 mg/kg or less of patient’s actual body weight.

The effects that lower dosing has had on SLE-associated hospitalizations was unknown, which inspired Dr. Nestor’s research.

The team conducted a case-crossover study within the Mass General Brigham SLE cohort.

Hospitalizations studied over a decade

Dr. Nestor and colleagues identified patients with SLE (via electronic health records) who had at least one visit for SLE and were prescribed HCQ between January 2011 and December 2021, the period over which the recommendations were made.

They identified patients who had been hospitalized during that decade with SLE as the primary discharge diagnosis.

Patients were excluded if they had non-SLE indications, such as kidney transplant or infection without a concomitant SLE flare.

Of 2,971 patients with SLE who used HCQ, 576 had at least one hospitalization with primary discharge diagnosis of SLE.

Of these, 108 were hospitalized for an SLE flare and had used HCQ prior to that hospitalization and had at least one control period with HCQ use during the study period.

All of the patients in the study had to have a case period and a control period, Dr. Nestor explained. The case period was 6 months on HCQ ending in hospitalization for lupus and the control period was 6 months on HCQ that did not end in hospitalization for lupus.
 

Significantly increased hospitalizations

Low-dose HCQ by weight-based dose (≤ 5 vs. > 5 mg/kg per day) and by non–weight-based dose (< 400 vs. 400 mg per day) were both associated with significantly increased hospitalizations for SLE (adjusted odds ratio, 4.41; 95% confidence interval, 1.50-12.98; and AOR, 3.48; 95% CI, 1.33-9.13, respectively).

The average age of the hospitalized group was 36 years. Most patients (92%) were female, 43.5% were White, and 32.4% were Black.

In calling for reassessment of the dosing, Dr. Nestor said, “We are protecting our patients against a very long-term side effect of hydroxychloroquine retinopathy. [It] typically takes 10-20 years to develop in our patients. But by doing that, we’re missing many of the short-term benefits from hydroxychloroquine in our patients, leading to more lupus flares, which leads to more end-organ damage.”

She said patients taking HCQ for lupus are asked to see an ophthalmologist once a year to monitor for the side effect, adding that rheumatologists and ophthalmologists could work together to adjust the guidelines.

Dr. Nestor suggested it’s possible that patients need higher doses of HCQ earlier in their disease and lower doses later. “Perhaps it’s just the patients who are particularly active who need the higher doses,” she said.

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

PHILADELPHIA – Patients with systemic lupus erythematosus treated with lower doses of hydroxychloroquine (HCQ) had an increased risk for hospitalization for flares, according to study results presented during a press conference at the annual meeting of the American College of Rheumatology.

Doses decreased with changing guidelines

Guidelines over the years have recommended decreasing doses of HCQ. In 2011, ophthalmology guidelines recommended limiting HCQ dosing to 6.5 mg/kg per day or less of ideal body weight to reduce the chance of retinopathy. For many patients, this required a dose lower than 400 mg/day, an amount frequently used to treat lupus.

In 2016, updated guidelines further lowered the dosage of HCQ, recommending 5 mg/kg or less of patient’s actual body weight.

The effects that lower dosing has had on SLE-associated hospitalizations was unknown, which inspired Dr. Nestor’s research.

The team conducted a case-crossover study within the Mass General Brigham SLE cohort.

Hospitalizations studied over a decade

Dr. Nestor and colleagues identified patients with SLE (via electronic health records) who had at least one visit for SLE and were prescribed HCQ between January 2011 and December 2021, the period over which the recommendations were made.

They identified patients who had been hospitalized during that decade with SLE as the primary discharge diagnosis.

Patients were excluded if they had non-SLE indications, such as kidney transplant or infection without a concomitant SLE flare.

Of 2,971 patients with SLE who used HCQ, 576 had at least one hospitalization with primary discharge diagnosis of SLE.

Of these, 108 were hospitalized for an SLE flare and had used HCQ prior to that hospitalization and had at least one control period with HCQ use during the study period.

All of the patients in the study had to have a case period and a control period, Dr. Nestor explained. The case period was 6 months on HCQ ending in hospitalization for lupus and the control period was 6 months on HCQ that did not end in hospitalization for lupus.
 

Significantly increased hospitalizations

Low-dose HCQ by weight-based dose (≤ 5 vs. > 5 mg/kg per day) and by non–weight-based dose (< 400 vs. 400 mg per day) were both associated with significantly increased hospitalizations for SLE (adjusted odds ratio, 4.41; 95% confidence interval, 1.50-12.98; and AOR, 3.48; 95% CI, 1.33-9.13, respectively).

The average age of the hospitalized group was 36 years. Most patients (92%) were female, 43.5% were White, and 32.4% were Black.

In calling for reassessment of the dosing, Dr. Nestor said, “We are protecting our patients against a very long-term side effect of hydroxychloroquine retinopathy. [It] typically takes 10-20 years to develop in our patients. But by doing that, we’re missing many of the short-term benefits from hydroxychloroquine in our patients, leading to more lupus flares, which leads to more end-organ damage.”

She said patients taking HCQ for lupus are asked to see an ophthalmologist once a year to monitor for the side effect, adding that rheumatologists and ophthalmologists could work together to adjust the guidelines.

Dr. Nestor suggested it’s possible that patients need higher doses of HCQ earlier in their disease and lower doses later. “Perhaps it’s just the patients who are particularly active who need the higher doses,” she said.

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

PHILADELPHIA – Oral remibrutinib was well tolerated and had a good safety profile over 24 weeks among patients with moderate to severe Sjögren syndrome (SS), according to new phase 2 data presented at the annual meeting of the American College of Rheumatology.

Thomas Dörner, MD, with the department of rheumatology and clinical immunology at Charité Universitätsmedizin Berlin, presented the data from the double-blind, randomized, placebo-controlled, proof-of-concept study.

The authors said the results of the study suggest that remibrutinib, a highly specific inhibitor of Bruton tyrosine kinase, has the potential to become the first effective oral disease-modifying therapy for SS.

The 73 participants in the study had moderate to severe SS. The baseline EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score was at least 5, EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) was at least 5, and anti-Ro/SSA antibody positivity was 3 months or less before screening. The patients’ unstimulated whole salivary flow rate was > 0 mL/min.

Overall, 73 patients (71 women) were randomly assigned to receive either remibrutinib 100 mg twice a day (n = 24), remibrutinib 100 mg four times a day (n = 25), or placebo (n = 24) between August 2019 and May 2021.

Remibrutinib met the primary endpoint and resulted in a statistically significant improvement in ESSDAI score for both regimens combined compared with placebo at week 24 (ESSDAI, –2.86).
 

Patient-reported outcomes similar to placebo

Patient-reported outcomes, including scores on ESSPRI, Functional Assessment of Chronic Illness Therapy–Fatigue, and EuroQol-5 Dimension, were similar in the treatment groups and the placebo group.

“All of the patients, including the placebo patients, improved over the time of the study,” Dr. Dörner said.

The average age of the patients was 51.8 years (range, 18-75 years). Groups were generally balanced with regard to demographic qualities and disease severity at baseline, and the patients represented the SS population well, Dr. Dörner said.

No severe adverse events were reported. Infections were the most frequently reported adverse events, and the rates were similar with the study drug and placebo. No notable liver abnormalities were reported in any of the groups.

Chrisanna Dobrowolski, MD, assistant professor of medicine at Icahn School of Medicine at Mount Sinai in New York, told this news organization, “Preliminary results are promising, but they failed to show improvements in patient-reported quality-of-life measures.

“Having statistical improvements in disease activity measures without clinically meaningful improvement in patient quality of life may limit the value of this treatment,” she said.

Dr. Dobrowolski added that the follow-up period of 6 months is short, and larger studies over a longer period are needed to better assess the effect on patients’ quality of life.

“Regardless, this is the first oral medication which has shown disease-modifying potential for the glandular symptoms of SS and is an exciting new avenue of investigation to be further explored,” she said.

Patients with SS 15 to 20 times more likely to develop B-cell lymphoma as a life-threatening complication. SS is a systemic autoimmune disease characterized by B-cell hyperactivation, lymphoid infiltration, progressive destruction of exocrine glands, and various complications outside the glands, the study authors wrote in the abstract.
 

Nearly 4 million in U.S. live with the disease

Nearly 4 million people in the United States live with the disease. Common symptoms include light sensitivity, dry eye, dry mouth, fatigue, and joint pain.

SS can be difficult to diagnose because the symptoms vary from person to person and can be confused with those caused by other diseases.

Ardy Fenando, MD, a rheumatology fellow with the University of Kansas Medical Center, said in an interview, “We need more therapies for Sjögren’s. Heterogeneity complicates the way we set the primary endpoints. Therefore, we haven’t had a proven treatment for Sjögren’s. This is supported by previous RCTs [randomized controlled trials] that failed to meet the primary end points.”

Dr. Dörner has relationships with AbbVie, Eli Lilly, Roche/Genentech, Janssen, Novartis, Bristol-Myers Squibb), and UCB. Other authors have various relationships with industry. Dr. Fenando and Dr. Dobrowolski have disclosed no relevant financial relationships.

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

PHILADELPHIA – Oral remibrutinib was well tolerated and had a good safety profile over 24 weeks among patients with moderate to severe Sjögren syndrome (SS), according to new phase 2 data presented at the annual meeting of the American College of Rheumatology.

Thomas Dörner, MD, with the department of rheumatology and clinical immunology at Charité Universitätsmedizin Berlin, presented the data from the double-blind, randomized, placebo-controlled, proof-of-concept study.

The authors said the results of the study suggest that remibrutinib, a highly specific inhibitor of Bruton tyrosine kinase, has the potential to become the first effective oral disease-modifying therapy for SS.

The 73 participants in the study had moderate to severe SS. The baseline EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score was at least 5, EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) was at least 5, and anti-Ro/SSA antibody positivity was 3 months or less before screening. The patients’ unstimulated whole salivary flow rate was > 0 mL/min.

Overall, 73 patients (71 women) were randomly assigned to receive either remibrutinib 100 mg twice a day (n = 24), remibrutinib 100 mg four times a day (n = 25), or placebo (n = 24) between August 2019 and May 2021.

Remibrutinib met the primary endpoint and resulted in a statistically significant improvement in ESSDAI score for both regimens combined compared with placebo at week 24 (ESSDAI, –2.86).
 

Patient-reported outcomes similar to placebo

Patient-reported outcomes, including scores on ESSPRI, Functional Assessment of Chronic Illness Therapy–Fatigue, and EuroQol-5 Dimension, were similar in the treatment groups and the placebo group.

“All of the patients, including the placebo patients, improved over the time of the study,” Dr. Dörner said.

The average age of the patients was 51.8 years (range, 18-75 years). Groups were generally balanced with regard to demographic qualities and disease severity at baseline, and the patients represented the SS population well, Dr. Dörner said.

No severe adverse events were reported. Infections were the most frequently reported adverse events, and the rates were similar with the study drug and placebo. No notable liver abnormalities were reported in any of the groups.

Chrisanna Dobrowolski, MD, assistant professor of medicine at Icahn School of Medicine at Mount Sinai in New York, told this news organization, “Preliminary results are promising, but they failed to show improvements in patient-reported quality-of-life measures.

“Having statistical improvements in disease activity measures without clinically meaningful improvement in patient quality of life may limit the value of this treatment,” she said.

Dr. Dobrowolski added that the follow-up period of 6 months is short, and larger studies over a longer period are needed to better assess the effect on patients’ quality of life.

“Regardless, this is the first oral medication which has shown disease-modifying potential for the glandular symptoms of SS and is an exciting new avenue of investigation to be further explored,” she said.

Patients with SS 15 to 20 times more likely to develop B-cell lymphoma as a life-threatening complication. SS is a systemic autoimmune disease characterized by B-cell hyperactivation, lymphoid infiltration, progressive destruction of exocrine glands, and various complications outside the glands, the study authors wrote in the abstract.
 

Nearly 4 million in U.S. live with the disease

Nearly 4 million people in the United States live with the disease. Common symptoms include light sensitivity, dry eye, dry mouth, fatigue, and joint pain.

SS can be difficult to diagnose because the symptoms vary from person to person and can be confused with those caused by other diseases.

Ardy Fenando, MD, a rheumatology fellow with the University of Kansas Medical Center, said in an interview, “We need more therapies for Sjögren’s. Heterogeneity complicates the way we set the primary endpoints. Therefore, we haven’t had a proven treatment for Sjögren’s. This is supported by previous RCTs [randomized controlled trials] that failed to meet the primary end points.”

Dr. Dörner has relationships with AbbVie, Eli Lilly, Roche/Genentech, Janssen, Novartis, Bristol-Myers Squibb), and UCB. Other authors have various relationships with industry. Dr. Fenando and Dr. Dobrowolski have disclosed no relevant financial relationships.

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

PHILADELPHIA – Oral remibrutinib was well tolerated and had a good safety profile over 24 weeks among patients with moderate to severe Sjögren syndrome (SS), according to new phase 2 data presented at the annual meeting of the American College of Rheumatology.

Thomas Dörner, MD, with the department of rheumatology and clinical immunology at Charité Universitätsmedizin Berlin, presented the data from the double-blind, randomized, placebo-controlled, proof-of-concept study.

The authors said the results of the study suggest that remibrutinib, a highly specific inhibitor of Bruton tyrosine kinase, has the potential to become the first effective oral disease-modifying therapy for SS.

The 73 participants in the study had moderate to severe SS. The baseline EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score was at least 5, EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) was at least 5, and anti-Ro/SSA antibody positivity was 3 months or less before screening. The patients’ unstimulated whole salivary flow rate was > 0 mL/min.

Overall, 73 patients (71 women) were randomly assigned to receive either remibrutinib 100 mg twice a day (n = 24), remibrutinib 100 mg four times a day (n = 25), or placebo (n = 24) between August 2019 and May 2021.

Remibrutinib met the primary endpoint and resulted in a statistically significant improvement in ESSDAI score for both regimens combined compared with placebo at week 24 (ESSDAI, –2.86).
 

Patient-reported outcomes similar to placebo

Patient-reported outcomes, including scores on ESSPRI, Functional Assessment of Chronic Illness Therapy–Fatigue, and EuroQol-5 Dimension, were similar in the treatment groups and the placebo group.

“All of the patients, including the placebo patients, improved over the time of the study,” Dr. Dörner said.

The average age of the patients was 51.8 years (range, 18-75 years). Groups were generally balanced with regard to demographic qualities and disease severity at baseline, and the patients represented the SS population well, Dr. Dörner said.

No severe adverse events were reported. Infections were the most frequently reported adverse events, and the rates were similar with the study drug and placebo. No notable liver abnormalities were reported in any of the groups.

Chrisanna Dobrowolski, MD, assistant professor of medicine at Icahn School of Medicine at Mount Sinai in New York, told this news organization, “Preliminary results are promising, but they failed to show improvements in patient-reported quality-of-life measures.

“Having statistical improvements in disease activity measures without clinically meaningful improvement in patient quality of life may limit the value of this treatment,” she said.

Dr. Dobrowolski added that the follow-up period of 6 months is short, and larger studies over a longer period are needed to better assess the effect on patients’ quality of life.

“Regardless, this is the first oral medication which has shown disease-modifying potential for the glandular symptoms of SS and is an exciting new avenue of investigation to be further explored,” she said.

Patients with SS 15 to 20 times more likely to develop B-cell lymphoma as a life-threatening complication. SS is a systemic autoimmune disease characterized by B-cell hyperactivation, lymphoid infiltration, progressive destruction of exocrine glands, and various complications outside the glands, the study authors wrote in the abstract.
 

Nearly 4 million in U.S. live with the disease

Nearly 4 million people in the United States live with the disease. Common symptoms include light sensitivity, dry eye, dry mouth, fatigue, and joint pain.

SS can be difficult to diagnose because the symptoms vary from person to person and can be confused with those caused by other diseases.

Ardy Fenando, MD, a rheumatology fellow with the University of Kansas Medical Center, said in an interview, “We need more therapies for Sjögren’s. Heterogeneity complicates the way we set the primary endpoints. Therefore, we haven’t had a proven treatment for Sjögren’s. This is supported by previous RCTs [randomized controlled trials] that failed to meet the primary end points.”

Dr. Dörner has relationships with AbbVie, Eli Lilly, Roche/Genentech, Janssen, Novartis, Bristol-Myers Squibb), and UCB. Other authors have various relationships with industry. Dr. Fenando and Dr. Dobrowolski have disclosed no relevant financial relationships.

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

PHILADELPHIA – In the first controlled clinical trial to compare the two drugs, rituximab and cyclophosphamide were similarly effective in improving lung function in patients with interstitial lung disease (ILD) associated with idiopathic inflammatory myositis and mixed connective tissue disease (CTD). The findings also revealed some nuanced findings that could help clarify which drug to use in specific patients.

“We feel that rituximab is a reasonable alternative to cyclophosphamide as a treatment in patients with these diseases,” said Toby Maher, MD, of the University of Southern California, Los Angeles, who presented results of an analysis of three disease subgroups from the RECITAL (Rituximab versus Cyclophosphamide for the Treatment of Connective Tissue Disease Associated Interstitial Lung Disease) study at the annual meeting of the American College of Rheumatology.

“We didn’t show it to be better, so I think you can reasonably choose between the two, but rituximab almost certainly has the advantage of being safer and better tolerated than cyclophosphamide,” Dr. Maher said in an interview. The findings were published simultaneously in The Lancet Respiratory Medicine.
 

Double-blind, double-dummy

RECITAL is a phase 2b, randomized, controlled trial to test the hypothesis that intravenous rituximab would be superior to cyclophosphamide for ILD-associated CTD.

The study included adults with three separate diagnoses: myositis (n = 44), mixed CTD (n = 16), and systemic sclerosis (SSc, n = 37). The study was done in the United Kingdom when Dr. Maher was with Imperial College London.

Patients in the rituximab group received 1,000 mg of IV treatment at baseline and 2 weeks, then placebo treatment every 4 weeks to week 20. Cyclophosphamide patients received 600 mg/m² of body surface area intravenously every 4 weeks for six doses.

“When we designed this study there was limited evidence for any treatment for any disease associated with ILD,” Dr. Maher said. “But cyclophosphamide brings with it many challenges. It can be poorly tolerated and carries issues like infertility and risk of bladder cancer.”
 

Improved lung function

While the study failed to meet its primary endpoint – superiority of rituximab versus cyclophosphamide – it did show that both drugs led to improvement in lung function, measured by the rate of change in forced vital capacity (FVC), as well as quality of life measures, Dr. Maher said.

“Overall by week 48, we saw about a 5% improvement in FVC in the cyclophosphamide group and approximately a 4% improvement in FVC from baseline in the rituximab group, suggesting that both drugs almost certainly had a positive benefit in this patient group,” he said.

But secondary outcomes varied somewhat across the different disease groups. Patients with SSc saw a slight deterioration with cyclophosphamide in the modified Rodnan skin score at 24 weeks (1.6 ± 5.7 units) but an improvement with rituximab (–3.4 ± 8.1 units).

“One area where we did see a difference was in the number of adverse events,” Dr. Maher said. “They were fewer in the rituximab arm – namely gastrointestinal disorders [and] nausea, which we saw quite frequently following cyclophosphamide. Also, they had fewer headaches, which we saw quite frequently following cyclophosphamide.”

Rituximab patients also had fewer infusion reactions, but the number of infections was similar between the two treatment groups, he said.

“The patient group that responded best to treatment was the myositis group,” Dr. Maher said in his presentation. “Cyclophosphamide actually appears to be more effective than rituximab in improving their disease. By the end of 48 weeks, the cyclophosphamide group actually gained about 400 mL in FVC, so a close to 20% improvement.”

The rituximab group had “a little bit of a drop-off” in efficacy from weeks 24 to 48, although the trial didn’t repeat dosing at 6 months, “which is what perhaps one might do in clinical practice,” he said.

Oliver Distler, MD, chair of rheumatology at the University Hospital Zürich, raised questions about concurrent corticosteroid use in study patients that may have caused a “spillover” in the study’s efficacy analysis. But Dr. Maher noted that steroid use was balanced in all treatment arms. Patients in the cyclophosphamide arm averaged 42.9 mg of hydrocortisone daily versus 37.6 mg daily in the rituximab arm. That represents a 12.3% reduction in steroid exposure for the latter.

Dr. Distler noted that the myositis population represented the bulk of those study patients on steroids. “So in the myositis subanalysis we do see a combination of high-dose steroid plus cyclophosphamide and rituximab.”

Dr. Maher disclosed relationships with Boehringer Ingelheim, Genentech, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, Trevi, CSL Behring, Pliant and Veracyte. Dr. Distler disclosed relationships with numerous pharmaceutical companies.






 

PHILADELPHIA – In the first controlled clinical trial to compare the two drugs, rituximab and cyclophosphamide were similarly effective in improving lung function in patients with interstitial lung disease (ILD) associated with idiopathic inflammatory myositis and mixed connective tissue disease (CTD). The findings also revealed some nuanced findings that could help clarify which drug to use in specific patients.

“We feel that rituximab is a reasonable alternative to cyclophosphamide as a treatment in patients with these diseases,” said Toby Maher, MD, of the University of Southern California, Los Angeles, who presented results of an analysis of three disease subgroups from the RECITAL (Rituximab versus Cyclophosphamide for the Treatment of Connective Tissue Disease Associated Interstitial Lung Disease) study at the annual meeting of the American College of Rheumatology.

“We didn’t show it to be better, so I think you can reasonably choose between the two, but rituximab almost certainly has the advantage of being safer and better tolerated than cyclophosphamide,” Dr. Maher said in an interview. The findings were published simultaneously in The Lancet Respiratory Medicine.
 

Double-blind, double-dummy

RECITAL is a phase 2b, randomized, controlled trial to test the hypothesis that intravenous rituximab would be superior to cyclophosphamide for ILD-associated CTD.

The study included adults with three separate diagnoses: myositis (n = 44), mixed CTD (n = 16), and systemic sclerosis (SSc, n = 37). The study was done in the United Kingdom when Dr. Maher was with Imperial College London.

Patients in the rituximab group received 1,000 mg of IV treatment at baseline and 2 weeks, then placebo treatment every 4 weeks to week 20. Cyclophosphamide patients received 600 mg/m² of body surface area intravenously every 4 weeks for six doses.

“When we designed this study there was limited evidence for any treatment for any disease associated with ILD,” Dr. Maher said. “But cyclophosphamide brings with it many challenges. It can be poorly tolerated and carries issues like infertility and risk of bladder cancer.”
 

Improved lung function

While the study failed to meet its primary endpoint – superiority of rituximab versus cyclophosphamide – it did show that both drugs led to improvement in lung function, measured by the rate of change in forced vital capacity (FVC), as well as quality of life measures, Dr. Maher said.

“Overall by week 48, we saw about a 5% improvement in FVC in the cyclophosphamide group and approximately a 4% improvement in FVC from baseline in the rituximab group, suggesting that both drugs almost certainly had a positive benefit in this patient group,” he said.

But secondary outcomes varied somewhat across the different disease groups. Patients with SSc saw a slight deterioration with cyclophosphamide in the modified Rodnan skin score at 24 weeks (1.6 ± 5.7 units) but an improvement with rituximab (–3.4 ± 8.1 units).

“One area where we did see a difference was in the number of adverse events,” Dr. Maher said. “They were fewer in the rituximab arm – namely gastrointestinal disorders [and] nausea, which we saw quite frequently following cyclophosphamide. Also, they had fewer headaches, which we saw quite frequently following cyclophosphamide.”

Rituximab patients also had fewer infusion reactions, but the number of infections was similar between the two treatment groups, he said.

“The patient group that responded best to treatment was the myositis group,” Dr. Maher said in his presentation. “Cyclophosphamide actually appears to be more effective than rituximab in improving their disease. By the end of 48 weeks, the cyclophosphamide group actually gained about 400 mL in FVC, so a close to 20% improvement.”

The rituximab group had “a little bit of a drop-off” in efficacy from weeks 24 to 48, although the trial didn’t repeat dosing at 6 months, “which is what perhaps one might do in clinical practice,” he said.

Oliver Distler, MD, chair of rheumatology at the University Hospital Zürich, raised questions about concurrent corticosteroid use in study patients that may have caused a “spillover” in the study’s efficacy analysis. But Dr. Maher noted that steroid use was balanced in all treatment arms. Patients in the cyclophosphamide arm averaged 42.9 mg of hydrocortisone daily versus 37.6 mg daily in the rituximab arm. That represents a 12.3% reduction in steroid exposure for the latter.

Dr. Distler noted that the myositis population represented the bulk of those study patients on steroids. “So in the myositis subanalysis we do see a combination of high-dose steroid plus cyclophosphamide and rituximab.”

Dr. Maher disclosed relationships with Boehringer Ingelheim, Genentech, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, Trevi, CSL Behring, Pliant and Veracyte. Dr. Distler disclosed relationships with numerous pharmaceutical companies.






 

PHILADELPHIA – In the first controlled clinical trial to compare the two drugs, rituximab and cyclophosphamide were similarly effective in improving lung function in patients with interstitial lung disease (ILD) associated with idiopathic inflammatory myositis and mixed connective tissue disease (CTD). The findings also revealed some nuanced findings that could help clarify which drug to use in specific patients.

“We feel that rituximab is a reasonable alternative to cyclophosphamide as a treatment in patients with these diseases,” said Toby Maher, MD, of the University of Southern California, Los Angeles, who presented results of an analysis of three disease subgroups from the RECITAL (Rituximab versus Cyclophosphamide for the Treatment of Connective Tissue Disease Associated Interstitial Lung Disease) study at the annual meeting of the American College of Rheumatology.

“We didn’t show it to be better, so I think you can reasonably choose between the two, but rituximab almost certainly has the advantage of being safer and better tolerated than cyclophosphamide,” Dr. Maher said in an interview. The findings were published simultaneously in The Lancet Respiratory Medicine.
 

Double-blind, double-dummy

RECITAL is a phase 2b, randomized, controlled trial to test the hypothesis that intravenous rituximab would be superior to cyclophosphamide for ILD-associated CTD.

The study included adults with three separate diagnoses: myositis (n = 44), mixed CTD (n = 16), and systemic sclerosis (SSc, n = 37). The study was done in the United Kingdom when Dr. Maher was with Imperial College London.

Patients in the rituximab group received 1,000 mg of IV treatment at baseline and 2 weeks, then placebo treatment every 4 weeks to week 20. Cyclophosphamide patients received 600 mg/m² of body surface area intravenously every 4 weeks for six doses.

“When we designed this study there was limited evidence for any treatment for any disease associated with ILD,” Dr. Maher said. “But cyclophosphamide brings with it many challenges. It can be poorly tolerated and carries issues like infertility and risk of bladder cancer.”
 

Improved lung function

While the study failed to meet its primary endpoint – superiority of rituximab versus cyclophosphamide – it did show that both drugs led to improvement in lung function, measured by the rate of change in forced vital capacity (FVC), as well as quality of life measures, Dr. Maher said.

“Overall by week 48, we saw about a 5% improvement in FVC in the cyclophosphamide group and approximately a 4% improvement in FVC from baseline in the rituximab group, suggesting that both drugs almost certainly had a positive benefit in this patient group,” he said.

But secondary outcomes varied somewhat across the different disease groups. Patients with SSc saw a slight deterioration with cyclophosphamide in the modified Rodnan skin score at 24 weeks (1.6 ± 5.7 units) but an improvement with rituximab (–3.4 ± 8.1 units).

“One area where we did see a difference was in the number of adverse events,” Dr. Maher said. “They were fewer in the rituximab arm – namely gastrointestinal disorders [and] nausea, which we saw quite frequently following cyclophosphamide. Also, they had fewer headaches, which we saw quite frequently following cyclophosphamide.”

Rituximab patients also had fewer infusion reactions, but the number of infections was similar between the two treatment groups, he said.

“The patient group that responded best to treatment was the myositis group,” Dr. Maher said in his presentation. “Cyclophosphamide actually appears to be more effective than rituximab in improving their disease. By the end of 48 weeks, the cyclophosphamide group actually gained about 400 mL in FVC, so a close to 20% improvement.”

The rituximab group had “a little bit of a drop-off” in efficacy from weeks 24 to 48, although the trial didn’t repeat dosing at 6 months, “which is what perhaps one might do in clinical practice,” he said.

Oliver Distler, MD, chair of rheumatology at the University Hospital Zürich, raised questions about concurrent corticosteroid use in study patients that may have caused a “spillover” in the study’s efficacy analysis. But Dr. Maher noted that steroid use was balanced in all treatment arms. Patients in the cyclophosphamide arm averaged 42.9 mg of hydrocortisone daily versus 37.6 mg daily in the rituximab arm. That represents a 12.3% reduction in steroid exposure for the latter.

Dr. Distler noted that the myositis population represented the bulk of those study patients on steroids. “So in the myositis subanalysis we do see a combination of high-dose steroid plus cyclophosphamide and rituximab.”

Dr. Maher disclosed relationships with Boehringer Ingelheim, Genentech, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, Trevi, CSL Behring, Pliant and Veracyte. Dr. Distler disclosed relationships with numerous pharmaceutical companies.






 

Researchers have found a link between age of diagnosis and various clinical characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The findings, presented at the annual meeting of the American College of Rheumatology, may have implications for research and treatment, especially in children.

AAV is a group of conditions characterized by the development of autoantibodies to the neutrophil proteins proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA).

The rare autoimmune condition can cause systemic inflammation and damage, sometimes permanent, to small- and medium-sized arteries. Clinical presentations vary and can include several organs, including skin, stomach, intestines, lung, and kidney, as well as airways in ear, nose, and throat.
 

Data limited on child vs. adult characteristics

AAV can be diagnosed in any decade of life, but clinical characteristics and outcomes often differ between children and adults, and data are limited. Studies often exclude children.

Lead author Jessica Bloom, MD, MSCS, a pediatric rheumatologist and assistant professor of pediatrics at Children’s Hospital Colorado, Aurora, and colleagues performed an analysis of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) who were enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies from 2013 to 2021.

Patients with eosinophilic GPA (EGPA) were analyzed separately. Children and young adults with EGPA were combined because of the small sample size (n = 87).

The groups were sorted by the age they were diagnosed: under 18 years old, 18-40, 40-65, and older than 65.
 

More than 1,000 patients included

Dr. Bloom’s team analyzed data from 1,020 patients: 61 diagnosed as children, 240 as young adults, 560 as middle-aged adults, and 159 diagnosed as older adults. At all ages, about nine out of 10 patients were White.

They found 852 (84%) had GPA and 165 (16%) had MPA. The analysis also showed 893 (92%) of patients with ANCA results were ANCA positive: 637 (65%) with PR3-ANCA, 247 (25%) with MPO-ANCA, and 9 (1%) with both.

Differences between age groups included:

• Children experienced more subglottic stenosis and alveolar hemorrhage than adults with the condition.
• About half of patients diagnosed in childhood received both cyclophosphamide and rituximab. That rate decreased with increasing age of diagnosis to as low as 14% for those diagnosed in older adulthood. 
• More females than males in all age groups were diagnosed with AAV, but the difference was most pronounced when diagnosed in childhood, and female predominance declined as age increased.
• Older adults experienced more neurologic disease and less musculoskeletal and sinus involvement.

Additionally, for those diagnosed after age 65, after adjusting for disease length and whether they were taking cyclophosphamide and/or rituximab, the Vasculitis Damage Index (VDI) and ANCA Vasculitis Index of Damage (AVID) scores were higher than for those diagnosed in childhood.

“However, these differences are no longer significant when medication toxicity and comorbidity-related items are excluded. Thus, differences in the VDI and AVID scores are driven by non–disease-specific damage,” Dr. Bloom said.
 

Bringing children into the clinical discussion

Dr. Bloom said in an interview that many pediatric rheumatologists believe kids with vasculitis are like small adults and should be treated similarly, but she said the picture may be more complex than that.

For example, the findings that children have more subglottic stenosis and alveolar hemorrhage than adults “may warrant more aggressive therapy,” she said. Children also have different growth and psychosocial risk factors during their disease course and may live longer with the disease than those in older age groups.

“Our study helps to point out these differences and bring children into the discussion,” Dr. Bloom said. “It also recognizes that damage scores used in studies and care may not adequately assess disease across the lifespan, as they are largely influenced by items not specific to the disease but rather medication toxicity and comorbidities, such as osteoporosis, cataracts, and malignancy.”

Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at Hospital for Special Surgery, New York, said in an interview that the work highlights interesting information about the fact that disease features are skewed differently in children – “in particular the higher likelihood of upper airway [subglottic] disease, and potentially severe lower airway disease [alveolar hemorrhage].”

However, from a practical standpoint, Dr. Spiera said, “I am not sure that this will change our clinical approach to different patients, but the differences in disease features and even the sex differences in terms of who are afflicted with GPA [more often children and more likely to be female] may offer insights into disease pathogenesis.”

Dr. Bloom received funding from the Vasculitis Clinical Research Consortium and Vasculitis Foundation to conduct this work as a VCRC-VF fellow. Several coauthors reported various conflicts of interest with pharmaceutical companies. Dr. Spiera declared no relevant financial relationships.

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

Researchers have found a link between age of diagnosis and various clinical characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The findings, presented at the annual meeting of the American College of Rheumatology, may have implications for research and treatment, especially in children.

AAV is a group of conditions characterized by the development of autoantibodies to the neutrophil proteins proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA).

The rare autoimmune condition can cause systemic inflammation and damage, sometimes permanent, to small- and medium-sized arteries. Clinical presentations vary and can include several organs, including skin, stomach, intestines, lung, and kidney, as well as airways in ear, nose, and throat.
 

Data limited on child vs. adult characteristics

AAV can be diagnosed in any decade of life, but clinical characteristics and outcomes often differ between children and adults, and data are limited. Studies often exclude children.

Lead author Jessica Bloom, MD, MSCS, a pediatric rheumatologist and assistant professor of pediatrics at Children’s Hospital Colorado, Aurora, and colleagues performed an analysis of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) who were enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies from 2013 to 2021.

Patients with eosinophilic GPA (EGPA) were analyzed separately. Children and young adults with EGPA were combined because of the small sample size (n = 87).

The groups were sorted by the age they were diagnosed: under 18 years old, 18-40, 40-65, and older than 65.
 

More than 1,000 patients included

Dr. Bloom’s team analyzed data from 1,020 patients: 61 diagnosed as children, 240 as young adults, 560 as middle-aged adults, and 159 diagnosed as older adults. At all ages, about nine out of 10 patients were White.

They found 852 (84%) had GPA and 165 (16%) had MPA. The analysis also showed 893 (92%) of patients with ANCA results were ANCA positive: 637 (65%) with PR3-ANCA, 247 (25%) with MPO-ANCA, and 9 (1%) with both.

Differences between age groups included:

• Children experienced more subglottic stenosis and alveolar hemorrhage than adults with the condition.
• About half of patients diagnosed in childhood received both cyclophosphamide and rituximab. That rate decreased with increasing age of diagnosis to as low as 14% for those diagnosed in older adulthood. 
• More females than males in all age groups were diagnosed with AAV, but the difference was most pronounced when diagnosed in childhood, and female predominance declined as age increased.
• Older adults experienced more neurologic disease and less musculoskeletal and sinus involvement.

Additionally, for those diagnosed after age 65, after adjusting for disease length and whether they were taking cyclophosphamide and/or rituximab, the Vasculitis Damage Index (VDI) and ANCA Vasculitis Index of Damage (AVID) scores were higher than for those diagnosed in childhood.

“However, these differences are no longer significant when medication toxicity and comorbidity-related items are excluded. Thus, differences in the VDI and AVID scores are driven by non–disease-specific damage,” Dr. Bloom said.
 

Bringing children into the clinical discussion

Dr. Bloom said in an interview that many pediatric rheumatologists believe kids with vasculitis are like small adults and should be treated similarly, but she said the picture may be more complex than that.

For example, the findings that children have more subglottic stenosis and alveolar hemorrhage than adults “may warrant more aggressive therapy,” she said. Children also have different growth and psychosocial risk factors during their disease course and may live longer with the disease than those in older age groups.

“Our study helps to point out these differences and bring children into the discussion,” Dr. Bloom said. “It also recognizes that damage scores used in studies and care may not adequately assess disease across the lifespan, as they are largely influenced by items not specific to the disease but rather medication toxicity and comorbidities, such as osteoporosis, cataracts, and malignancy.”

Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at Hospital for Special Surgery, New York, said in an interview that the work highlights interesting information about the fact that disease features are skewed differently in children – “in particular the higher likelihood of upper airway [subglottic] disease, and potentially severe lower airway disease [alveolar hemorrhage].”

However, from a practical standpoint, Dr. Spiera said, “I am not sure that this will change our clinical approach to different patients, but the differences in disease features and even the sex differences in terms of who are afflicted with GPA [more often children and more likely to be female] may offer insights into disease pathogenesis.”

Dr. Bloom received funding from the Vasculitis Clinical Research Consortium and Vasculitis Foundation to conduct this work as a VCRC-VF fellow. Several coauthors reported various conflicts of interest with pharmaceutical companies. Dr. Spiera declared no relevant financial relationships.

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

Researchers have found a link between age of diagnosis and various clinical characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The findings, presented at the annual meeting of the American College of Rheumatology, may have implications for research and treatment, especially in children.

AAV is a group of conditions characterized by the development of autoantibodies to the neutrophil proteins proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA).

The rare autoimmune condition can cause systemic inflammation and damage, sometimes permanent, to small- and medium-sized arteries. Clinical presentations vary and can include several organs, including skin, stomach, intestines, lung, and kidney, as well as airways in ear, nose, and throat.
 

Data limited on child vs. adult characteristics

AAV can be diagnosed in any decade of life, but clinical characteristics and outcomes often differ between children and adults, and data are limited. Studies often exclude children.

Lead author Jessica Bloom, MD, MSCS, a pediatric rheumatologist and assistant professor of pediatrics at Children’s Hospital Colorado, Aurora, and colleagues performed an analysis of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) who were enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies from 2013 to 2021.

Patients with eosinophilic GPA (EGPA) were analyzed separately. Children and young adults with EGPA were combined because of the small sample size (n = 87).

The groups were sorted by the age they were diagnosed: under 18 years old, 18-40, 40-65, and older than 65.
 

More than 1,000 patients included

Dr. Bloom’s team analyzed data from 1,020 patients: 61 diagnosed as children, 240 as young adults, 560 as middle-aged adults, and 159 diagnosed as older adults. At all ages, about nine out of 10 patients were White.

They found 852 (84%) had GPA and 165 (16%) had MPA. The analysis also showed 893 (92%) of patients with ANCA results were ANCA positive: 637 (65%) with PR3-ANCA, 247 (25%) with MPO-ANCA, and 9 (1%) with both.

Differences between age groups included:

• Children experienced more subglottic stenosis and alveolar hemorrhage than adults with the condition.
• About half of patients diagnosed in childhood received both cyclophosphamide and rituximab. That rate decreased with increasing age of diagnosis to as low as 14% for those diagnosed in older adulthood. 
• More females than males in all age groups were diagnosed with AAV, but the difference was most pronounced when diagnosed in childhood, and female predominance declined as age increased.
• Older adults experienced more neurologic disease and less musculoskeletal and sinus involvement.

Additionally, for those diagnosed after age 65, after adjusting for disease length and whether they were taking cyclophosphamide and/or rituximab, the Vasculitis Damage Index (VDI) and ANCA Vasculitis Index of Damage (AVID) scores were higher than for those diagnosed in childhood.

“However, these differences are no longer significant when medication toxicity and comorbidity-related items are excluded. Thus, differences in the VDI and AVID scores are driven by non–disease-specific damage,” Dr. Bloom said.
 

Bringing children into the clinical discussion

Dr. Bloom said in an interview that many pediatric rheumatologists believe kids with vasculitis are like small adults and should be treated similarly, but she said the picture may be more complex than that.

For example, the findings that children have more subglottic stenosis and alveolar hemorrhage than adults “may warrant more aggressive therapy,” she said. Children also have different growth and psychosocial risk factors during their disease course and may live longer with the disease than those in older age groups.

“Our study helps to point out these differences and bring children into the discussion,” Dr. Bloom said. “It also recognizes that damage scores used in studies and care may not adequately assess disease across the lifespan, as they are largely influenced by items not specific to the disease but rather medication toxicity and comorbidities, such as osteoporosis, cataracts, and malignancy.”

Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at Hospital for Special Surgery, New York, said in an interview that the work highlights interesting information about the fact that disease features are skewed differently in children – “in particular the higher likelihood of upper airway [subglottic] disease, and potentially severe lower airway disease [alveolar hemorrhage].”

However, from a practical standpoint, Dr. Spiera said, “I am not sure that this will change our clinical approach to different patients, but the differences in disease features and even the sex differences in terms of who are afflicted with GPA [more often children and more likely to be female] may offer insights into disease pathogenesis.”

Dr. Bloom received funding from the Vasculitis Clinical Research Consortium and Vasculitis Foundation to conduct this work as a VCRC-VF fellow. Several coauthors reported various conflicts of interest with pharmaceutical companies. Dr. Spiera declared no relevant financial relationships.

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

AT ACR 2022

PHILADELPHIA – The first consensus screening guidelines for patients with idiopathic inflammatory myopathy (IIM) provide recommendations on risk stratification for individuals, basic and enhanced screening protocols, and screening frequency.

The recommendations, issued by the International Myositis Assessment and Clinical Studies Group (IMACS), stratify cancer risk for individual patients into low, intermediate, or high categories based on the IIM disease subtype, autoantibody status, and clinical features, reported Alexander Oldroyd, PhD, MSc, MBChB of the University of Manchester, England.

Neil Osterweil/MDedge News

“There’s a big unmet need for cancer screening. One in four adults with myositis has cancer, either 3 years before or after a diagnosis of myositis. It’s one of the leading causes of death in these patients, and they’re overwhelmingly diagnosed at a late stage, so we need standardized approaches to get early diagnosis,” he said in an interview at the annual meeting of the American College of Rheumatology.

Sharon Kolasinski, MD, of the University of Pennsylvania in Philadelphia, said in an interview that the guideline is a welcome development for rheumatologists. Dr. Kolasinski moderated the session where Dr. Oldroyd described the guideline, but she was not involved in its formulation.

“I think that we all have wondered for a very long time: What is the optimal cancer screening for myositis patients? We all worry that the onset of their diseases is associated with a coincident cancer, or that they will develop it soon,” she said.

Dr. Oldroyd emphasized that all patients with myositis have elevated risk for cancer compared with the general population and that the guideline categories of low, intermediate, and high are relative only to patients with IIM.
 

International consensus

The data on which the recommendations are based come from a systematic review and meta-analysis by Dr. Oldroyd and colleagues of 69 studies on cancer risk factors and 9 on IIM-specific cancer screening.

The authors of that paper found that the dermatomyositis subtype, older age, male sex, dysphagia, cutaneous ulceration and antitranscriptional intermediary factor-1 gamma (anti-TIF1-gamma) positivity were associated with significantly increased risk of cancer.

In contrast, polymyositis and clinically amyopathic dermatomyositis subtypes, Raynaud’s phenomenon, interstitial lung disease, very high serum creatine kinase or lactate dehydrogenase levels, and positivity for anti-Jo1 or anti-EJ antibodies were associated with significantly reduced risk of cancer.

The consensus recommendations were developed with anonymous contributions from 75 expert participants in 22 countries, with additional input from 3 patient partners.
 

Do this

The guideline lists 18 recommendations, of which 13 are strong and 5 are conditional.

An example of a strong recommendation is number 3, based on a moderate level of evidences:

“All adult IIM patients, irrespective of cancer risk, should continue to participate in country/region-specific age and sex appropriate cancer screening programs,” the guideline recommends.

Patients with verified inclusion body myositis or juvenile-onset IIM do not, however, require routine screening for myositis-associated cancer, the guideline says (recommendations 1 and 2).

There are also recommendations that all adults with new-onset IIM be tested for myositis-specific and myositis-associated autoantibodies to assist in stratifying patients by risk category.

The guideline divides screening recommendations into basic and enhanced. The basic screening should include a comprehensive history and physical exam, complete blood count, liver functions tests, erythrocyte sedimentation rates/plasma viscosity, serum protein electrophoresis, urinalysis, and chest x-ray.

Adults with IIM who are determined to be at low risk for IIM-related cancer should have basic cancer screening at the time of IIM diagnosis. Adults with intermediate risk should undergo both basic and enhanced screening at the time of IIM diagnosis, and those with high risk should undergo enhanced screening at the time of myositis diagnosis, with basic screening annually for 3 years, the recommendations say.
 

Consider doing this

Conditional recommendations (“clinicians should consider ...”) include the use of PET/CT for adults at high risk for cancer when an underlying cancer has not been detected at the time of IIM diagnosis. They also include a single screening test for anti-TIF1-gamma positive dermatomyositis patients whose disease onset was after age 40 and who have at least one additional risk factor.

Also conditionally recommended are upper and lower gastrointestinal endoscopy for patients at high risk when an underlying cancer is not found at the time of IIM diagnosis, nasoendoscopy in geographical regions with elevated risk for nasopharyngeal cancers, and screening for all IIM patients with red-flag symptoms or clinical features of cancer, including unexplained weight loss, family history of cancer, smoking, unexplained fever, or night sweats.
 

Guided steps

“I think clinicians have a lot of questions such as, ‘well, what should I do, when should I do it?’ These are important clinical questions, and we need guidance about this. We need to balance comprehensiveness with cost-effectiveness, and we need expert opinion about what steps we should take now and which should we take later,” Dr. Kolasinski said.

The guideline development process was supported by the University of Manchester, IMACS, National Institute for Health Research (United Kingdom), National Institutes of Health, National Health Service Northern Care Alliance, The Myositis Association, Myositis UK, University of Pittsburgh, Versus Arthritis, and the Center for Musculoskeletal Research. Dr. Oldroyd and Dr. Kolasinski reported having no relevant conflicts of interest.

AT ACR 2022

PHILADELPHIA – The first consensus screening guidelines for patients with idiopathic inflammatory myopathy (IIM) provide recommendations on risk stratification for individuals, basic and enhanced screening protocols, and screening frequency.

The recommendations, issued by the International Myositis Assessment and Clinical Studies Group (IMACS), stratify cancer risk for individual patients into low, intermediate, or high categories based on the IIM disease subtype, autoantibody status, and clinical features, reported Alexander Oldroyd, PhD, MSc, MBChB of the University of Manchester, England.

Neil Osterweil/MDedge News

“There’s a big unmet need for cancer screening. One in four adults with myositis has cancer, either 3 years before or after a diagnosis of myositis. It’s one of the leading causes of death in these patients, and they’re overwhelmingly diagnosed at a late stage, so we need standardized approaches to get early diagnosis,” he said in an interview at the annual meeting of the American College of Rheumatology.

Sharon Kolasinski, MD, of the University of Pennsylvania in Philadelphia, said in an interview that the guideline is a welcome development for rheumatologists. Dr. Kolasinski moderated the session where Dr. Oldroyd described the guideline, but she was not involved in its formulation.

“I think that we all have wondered for a very long time: What is the optimal cancer screening for myositis patients? We all worry that the onset of their diseases is associated with a coincident cancer, or that they will develop it soon,” she said.

Dr. Oldroyd emphasized that all patients with myositis have elevated risk for cancer compared with the general population and that the guideline categories of low, intermediate, and high are relative only to patients with IIM.
 

International consensus

The data on which the recommendations are based come from a systematic review and meta-analysis by Dr. Oldroyd and colleagues of 69 studies on cancer risk factors and 9 on IIM-specific cancer screening.

The authors of that paper found that the dermatomyositis subtype, older age, male sex, dysphagia, cutaneous ulceration and antitranscriptional intermediary factor-1 gamma (anti-TIF1-gamma) positivity were associated with significantly increased risk of cancer.

In contrast, polymyositis and clinically amyopathic dermatomyositis subtypes, Raynaud’s phenomenon, interstitial lung disease, very high serum creatine kinase or lactate dehydrogenase levels, and positivity for anti-Jo1 or anti-EJ antibodies were associated with significantly reduced risk of cancer.

The consensus recommendations were developed with anonymous contributions from 75 expert participants in 22 countries, with additional input from 3 patient partners.
 

Do this

The guideline lists 18 recommendations, of which 13 are strong and 5 are conditional.

An example of a strong recommendation is number 3, based on a moderate level of evidences:

“All adult IIM patients, irrespective of cancer risk, should continue to participate in country/region-specific age and sex appropriate cancer screening programs,” the guideline recommends.

Patients with verified inclusion body myositis or juvenile-onset IIM do not, however, require routine screening for myositis-associated cancer, the guideline says (recommendations 1 and 2).

There are also recommendations that all adults with new-onset IIM be tested for myositis-specific and myositis-associated autoantibodies to assist in stratifying patients by risk category.

The guideline divides screening recommendations into basic and enhanced. The basic screening should include a comprehensive history and physical exam, complete blood count, liver functions tests, erythrocyte sedimentation rates/plasma viscosity, serum protein electrophoresis, urinalysis, and chest x-ray.

Adults with IIM who are determined to be at low risk for IIM-related cancer should have basic cancer screening at the time of IIM diagnosis. Adults with intermediate risk should undergo both basic and enhanced screening at the time of IIM diagnosis, and those with high risk should undergo enhanced screening at the time of myositis diagnosis, with basic screening annually for 3 years, the recommendations say.
 

Consider doing this

Conditional recommendations (“clinicians should consider ...”) include the use of PET/CT for adults at high risk for cancer when an underlying cancer has not been detected at the time of IIM diagnosis. They also include a single screening test for anti-TIF1-gamma positive dermatomyositis patients whose disease onset was after age 40 and who have at least one additional risk factor.

Also conditionally recommended are upper and lower gastrointestinal endoscopy for patients at high risk when an underlying cancer is not found at the time of IIM diagnosis, nasoendoscopy in geographical regions with elevated risk for nasopharyngeal cancers, and screening for all IIM patients with red-flag symptoms or clinical features of cancer, including unexplained weight loss, family history of cancer, smoking, unexplained fever, or night sweats.
 

Guided steps

“I think clinicians have a lot of questions such as, ‘well, what should I do, when should I do it?’ These are important clinical questions, and we need guidance about this. We need to balance comprehensiveness with cost-effectiveness, and we need expert opinion about what steps we should take now and which should we take later,” Dr. Kolasinski said.

The guideline development process was supported by the University of Manchester, IMACS, National Institute for Health Research (United Kingdom), National Institutes of Health, National Health Service Northern Care Alliance, The Myositis Association, Myositis UK, University of Pittsburgh, Versus Arthritis, and the Center for Musculoskeletal Research. Dr. Oldroyd and Dr. Kolasinski reported having no relevant conflicts of interest.

AT ACR 2022

PHILADELPHIA – The first consensus screening guidelines for patients with idiopathic inflammatory myopathy (IIM) provide recommendations on risk stratification for individuals, basic and enhanced screening protocols, and screening frequency.

The recommendations, issued by the International Myositis Assessment and Clinical Studies Group (IMACS), stratify cancer risk for individual patients into low, intermediate, or high categories based on the IIM disease subtype, autoantibody status, and clinical features, reported Alexander Oldroyd, PhD, MSc, MBChB of the University of Manchester, England.

Neil Osterweil/MDedge News

“There’s a big unmet need for cancer screening. One in four adults with myositis has cancer, either 3 years before or after a diagnosis of myositis. It’s one of the leading causes of death in these patients, and they’re overwhelmingly diagnosed at a late stage, so we need standardized approaches to get early diagnosis,” he said in an interview at the annual meeting of the American College of Rheumatology.

Sharon Kolasinski, MD, of the University of Pennsylvania in Philadelphia, said in an interview that the guideline is a welcome development for rheumatologists. Dr. Kolasinski moderated the session where Dr. Oldroyd described the guideline, but she was not involved in its formulation.

“I think that we all have wondered for a very long time: What is the optimal cancer screening for myositis patients? We all worry that the onset of their diseases is associated with a coincident cancer, or that they will develop it soon,” she said.

Dr. Oldroyd emphasized that all patients with myositis have elevated risk for cancer compared with the general population and that the guideline categories of low, intermediate, and high are relative only to patients with IIM.
 

International consensus

The data on which the recommendations are based come from a systematic review and meta-analysis by Dr. Oldroyd and colleagues of 69 studies on cancer risk factors and 9 on IIM-specific cancer screening.

The authors of that paper found that the dermatomyositis subtype, older age, male sex, dysphagia, cutaneous ulceration and antitranscriptional intermediary factor-1 gamma (anti-TIF1-gamma) positivity were associated with significantly increased risk of cancer.

In contrast, polymyositis and clinically amyopathic dermatomyositis subtypes, Raynaud’s phenomenon, interstitial lung disease, very high serum creatine kinase or lactate dehydrogenase levels, and positivity for anti-Jo1 or anti-EJ antibodies were associated with significantly reduced risk of cancer.

The consensus recommendations were developed with anonymous contributions from 75 expert participants in 22 countries, with additional input from 3 patient partners.
 

Do this

The guideline lists 18 recommendations, of which 13 are strong and 5 are conditional.

An example of a strong recommendation is number 3, based on a moderate level of evidences:

“All adult IIM patients, irrespective of cancer risk, should continue to participate in country/region-specific age and sex appropriate cancer screening programs,” the guideline recommends.

Patients with verified inclusion body myositis or juvenile-onset IIM do not, however, require routine screening for myositis-associated cancer, the guideline says (recommendations 1 and 2).

There are also recommendations that all adults with new-onset IIM be tested for myositis-specific and myositis-associated autoantibodies to assist in stratifying patients by risk category.

The guideline divides screening recommendations into basic and enhanced. The basic screening should include a comprehensive history and physical exam, complete blood count, liver functions tests, erythrocyte sedimentation rates/plasma viscosity, serum protein electrophoresis, urinalysis, and chest x-ray.

Adults with IIM who are determined to be at low risk for IIM-related cancer should have basic cancer screening at the time of IIM diagnosis. Adults with intermediate risk should undergo both basic and enhanced screening at the time of IIM diagnosis, and those with high risk should undergo enhanced screening at the time of myositis diagnosis, with basic screening annually for 3 years, the recommendations say.
 

Consider doing this

Conditional recommendations (“clinicians should consider ...”) include the use of PET/CT for adults at high risk for cancer when an underlying cancer has not been detected at the time of IIM diagnosis. They also include a single screening test for anti-TIF1-gamma positive dermatomyositis patients whose disease onset was after age 40 and who have at least one additional risk factor.

Also conditionally recommended are upper and lower gastrointestinal endoscopy for patients at high risk when an underlying cancer is not found at the time of IIM diagnosis, nasoendoscopy in geographical regions with elevated risk for nasopharyngeal cancers, and screening for all IIM patients with red-flag symptoms or clinical features of cancer, including unexplained weight loss, family history of cancer, smoking, unexplained fever, or night sweats.
 

Guided steps

“I think clinicians have a lot of questions such as, ‘well, what should I do, when should I do it?’ These are important clinical questions, and we need guidance about this. We need to balance comprehensiveness with cost-effectiveness, and we need expert opinion about what steps we should take now and which should we take later,” Dr. Kolasinski said.

The guideline development process was supported by the University of Manchester, IMACS, National Institute for Health Research (United Kingdom), National Institutes of Health, National Health Service Northern Care Alliance, The Myositis Association, Myositis UK, University of Pittsburgh, Versus Arthritis, and the Center for Musculoskeletal Research. Dr. Oldroyd and Dr. Kolasinski reported having no relevant conflicts of interest.

The field of “reproductive rheumatology” has received growing attention in recent years as we learn more about how autoimmune rheumatic diseases and their treatment affect women of reproductive age. In 2020, the American College of Rheumatology published a comprehensive guideline that includes recommendations and supporting evidence for managing issues related to reproductive health in patients with rheumatic diseases and has since launched an ongoing Reproductive Health Initiative, with the goal of translating established guidelines into practice through various education and awareness campaigns. One area addressed by the guideline that comes up commonly in practice but receives less attention and research is the use of assisted reproductive technology (ART) in patients with rheumatic diseases.

Literature is conflicting regarding whether patients with autoimmune rheumatic diseases are inherently at increased risk for infertility, defined as failure to achieve a clinical pregnancy after 12 months or more of regular unprotected intercourse, or subfertility, defined as a delay in conception. Regardless, several factors indirectly contribute to a disproportionate risk for infertility or subfertility in this patient population, including active inflammatory disease, reduced ovarian reserve, and medications.

Patients with subfertility or infertility who desire pregnancy may pursue ovulation induction with timed intercourse or intrauterine insemination, in vitro fertilization (IVF)/intracytoplasmic sperm injection with either embryo transfer, or gestational surrogacy. Those who require treatment with cyclophosphamide or who plan to defer pregnancy for whatever reason can opt for oocyte cryopreservation (colloquially known as “egg freezing”). For IVF and oocyte cryopreservation, controlled ovarian stimulation is typically the first step (except in unstimulated, or “natural cycle,” IVF).

Various protocols are used for ovarian stimulation and ovulation induction, the nuances of which are beyond the scope of this article. In general, ovarian stimulation involves gonadotropin therapy (follicle-stimulating hormone and/or human menopausal gonadotropin) administered via scheduled subcutaneous injections to stimulate follicular growth, as well as gonadotropin-releasing hormone (GnRH) agonists or antagonists to suppress luteinizing hormone, preventing ovulation. Adjunctive oral therapy (clomiphene citrate or letrozole, an aromatase inhibitor) may be used as well. The patient has frequent lab monitoring of hormone levels and transvaginal ultrasounds to measure follicle number and size and, when the timing is right, receives an “ovulation trigger” – either human chorionic gonadotropin or GnRH agonist, depending on the protocol. At this point, transvaginal ultrasound–guided egg retrieval is done under sedation. Recovered oocytes are then either frozen for later use or fertilized in the lab for embryo transfer. Lastly, exogenous hormones are often used: estrogen to support frozen embryo transfers and progesterone for so-called luteal phase support.

ART is not contraindicated in patients with autoimmune rheumatic diseases, but there may be additional factors to consider, particularly for those with systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and antiphospholipid antibodies (aPL) without clinical APS.

Ovarian stimulation elevates estrogen levels to varying degrees depending on the patient and the medications used. In all cases, though, peak levels are significantly lower than levels reached during pregnancy. It is well established that elevated estrogen – whether from hormone therapies or pregnancy – significantly increases thrombotic risk, even in healthy people. High-risk patients should receive low-molecular-weight heparin – a prophylactic dose for patients with either positive aPL without clinical APS (including those with SLE) or with obstetric APS, and a therapeutic dose for those with thrombotic APS – during ART procedures.

In patients with SLE, another concern is that increased estrogen will cause disease flare. One case series published in 2017 reported 37 patients with SLE and/or APS who underwent 97 IVF cycles, of which 8% were complicated by flare or thrombotic events. Notably, half of these complications occurred in patients who stopped prescribed therapies (immunomodulatory therapy in two patients with SLE, anticoagulation in two patients with APS) after failure to conceive. In a separate study from 2000 including 19 patients with SLE, APS, or high-titer aPL who underwent 68 IVF cycles, 19% of cycles in patients with SLE were complicated by flare, and no thrombotic events occurred in the cohort. The authors concluded that ovulation induction does not exacerbate SLE or APS. In these studies, the overall pregnancy rates were felt to be consistent with those achieved by the general population through IVF. Although obstetric complications, such as preeclampsia and preterm delivery, were reported in about half of the pregnancies described, these are known to occur more frequently in those with SLE and APS, especially when active disease or other risk factors are present. There are no large-scale, controlled studies evaluating ART outcomes in patients with autoimmune rheumatic diseases to date.

Finally, ovarian hyperstimulation syndrome (OHSS) is an increasingly rare but severe complication of ovarian stimulation. OHSS is characterized by capillary leak, fluid overload, and cytokine release syndrome and can lead to thromboembolic events. Comorbidities like hypertension and renal failure, which can go along with autoimmune rheumatic diseases, are risk factors for OHSS. The use of human chorionic gonadotropin to trigger ovulation is also associated with an increased risk for OHSS, so a GnRH agonist trigger may be preferable.

The ACR guideline recommends that individuals with any of these underlying conditions undergo ART only in expert centers. The ovarian stimulation protocol needs to be tailored to the individual patient to minimize risk and optimize outcomes. The overall goal when managing patients with autoimmune rheumatic diseases during ART is to establish and maintain disease control with pregnancy-compatible medications (when pregnancy is the goal). With adequate planning, appropriate treatment, and collaboration between obstetricians and rheumatologists, individuals with autoimmune rheumatic diseases can safely pursue ART and go on to have successful pregnancies.

Dr. Siegel is a 2022-2023 UCB Women’s Health rheumatology fellow in the rheumatology reproductive health program of the Barbara Volcker Center for Women and Rheumatic Diseases at Hospital for Special Surgery/Weill Cornell Medicine, New York. Her clinical and research focus is on reproductive health issues in individuals with rheumatic disease. Dr. Chan is an assistant professor at Weill Cornell Medical College and an attending physician at Hospital for Special Surgery and Memorial Sloan Kettering Cancer Center in New York. Before moving to New York City, she spent 7 years in private practice in Rhode Island and was a columnist for a monthly rheumatology publication, writing about the challenges of starting life as a full-fledged rheumatologist in a private practice. Follow Dr Chan on Twitter. Dr. Siegel and Dr. Chan disclosed no relevant financial relationships.

A version of this article – an editorial collaboration between Medscape and the Hospital for Special Surgery – first appeared on Medscape.com.

The field of “reproductive rheumatology” has received growing attention in recent years as we learn more about how autoimmune rheumatic diseases and their treatment affect women of reproductive age. In 2020, the American College of Rheumatology published a comprehensive guideline that includes recommendations and supporting evidence for managing issues related to reproductive health in patients with rheumatic diseases and has since launched an ongoing Reproductive Health Initiative, with the goal of translating established guidelines into practice through various education and awareness campaigns. One area addressed by the guideline that comes up commonly in practice but receives less attention and research is the use of assisted reproductive technology (ART) in patients with rheumatic diseases.

Literature is conflicting regarding whether patients with autoimmune rheumatic diseases are inherently at increased risk for infertility, defined as failure to achieve a clinical pregnancy after 12 months or more of regular unprotected intercourse, or subfertility, defined as a delay in conception. Regardless, several factors indirectly contribute to a disproportionate risk for infertility or subfertility in this patient population, including active inflammatory disease, reduced ovarian reserve, and medications.

Patients with subfertility or infertility who desire pregnancy may pursue ovulation induction with timed intercourse or intrauterine insemination, in vitro fertilization (IVF)/intracytoplasmic sperm injection with either embryo transfer, or gestational surrogacy. Those who require treatment with cyclophosphamide or who plan to defer pregnancy for whatever reason can opt for oocyte cryopreservation (colloquially known as “egg freezing”). For IVF and oocyte cryopreservation, controlled ovarian stimulation is typically the first step (except in unstimulated, or “natural cycle,” IVF).

Various protocols are used for ovarian stimulation and ovulation induction, the nuances of which are beyond the scope of this article. In general, ovarian stimulation involves gonadotropin therapy (follicle-stimulating hormone and/or human menopausal gonadotropin) administered via scheduled subcutaneous injections to stimulate follicular growth, as well as gonadotropin-releasing hormone (GnRH) agonists or antagonists to suppress luteinizing hormone, preventing ovulation. Adjunctive oral therapy (clomiphene citrate or letrozole, an aromatase inhibitor) may be used as well. The patient has frequent lab monitoring of hormone levels and transvaginal ultrasounds to measure follicle number and size and, when the timing is right, receives an “ovulation trigger” – either human chorionic gonadotropin or GnRH agonist, depending on the protocol. At this point, transvaginal ultrasound–guided egg retrieval is done under sedation. Recovered oocytes are then either frozen for later use or fertilized in the lab for embryo transfer. Lastly, exogenous hormones are often used: estrogen to support frozen embryo transfers and progesterone for so-called luteal phase support.

ART is not contraindicated in patients with autoimmune rheumatic diseases, but there may be additional factors to consider, particularly for those with systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and antiphospholipid antibodies (aPL) without clinical APS.

Ovarian stimulation elevates estrogen levels to varying degrees depending on the patient and the medications used. In all cases, though, peak levels are significantly lower than levels reached during pregnancy. It is well established that elevated estrogen – whether from hormone therapies or pregnancy – significantly increases thrombotic risk, even in healthy people. High-risk patients should receive low-molecular-weight heparin – a prophylactic dose for patients with either positive aPL without clinical APS (including those with SLE) or with obstetric APS, and a therapeutic dose for those with thrombotic APS – during ART procedures.

In patients with SLE, another concern is that increased estrogen will cause disease flare. One case series published in 2017 reported 37 patients with SLE and/or APS who underwent 97 IVF cycles, of which 8% were complicated by flare or thrombotic events. Notably, half of these complications occurred in patients who stopped prescribed therapies (immunomodulatory therapy in two patients with SLE, anticoagulation in two patients with APS) after failure to conceive. In a separate study from 2000 including 19 patients with SLE, APS, or high-titer aPL who underwent 68 IVF cycles, 19% of cycles in patients with SLE were complicated by flare, and no thrombotic events occurred in the cohort. The authors concluded that ovulation induction does not exacerbate SLE or APS. In these studies, the overall pregnancy rates were felt to be consistent with those achieved by the general population through IVF. Although obstetric complications, such as preeclampsia and preterm delivery, were reported in about half of the pregnancies described, these are known to occur more frequently in those with SLE and APS, especially when active disease or other risk factors are present. There are no large-scale, controlled studies evaluating ART outcomes in patients with autoimmune rheumatic diseases to date.

Finally, ovarian hyperstimulation syndrome (OHSS) is an increasingly rare but severe complication of ovarian stimulation. OHSS is characterized by capillary leak, fluid overload, and cytokine release syndrome and can lead to thromboembolic events. Comorbidities like hypertension and renal failure, which can go along with autoimmune rheumatic diseases, are risk factors for OHSS. The use of human chorionic gonadotropin to trigger ovulation is also associated with an increased risk for OHSS, so a GnRH agonist trigger may be preferable.

The ACR guideline recommends that individuals with any of these underlying conditions undergo ART only in expert centers. The ovarian stimulation protocol needs to be tailored to the individual patient to minimize risk and optimize outcomes. The overall goal when managing patients with autoimmune rheumatic diseases during ART is to establish and maintain disease control with pregnancy-compatible medications (when pregnancy is the goal). With adequate planning, appropriate treatment, and collaboration between obstetricians and rheumatologists, individuals with autoimmune rheumatic diseases can safely pursue ART and go on to have successful pregnancies.

Dr. Siegel is a 2022-2023 UCB Women’s Health rheumatology fellow in the rheumatology reproductive health program of the Barbara Volcker Center for Women and Rheumatic Diseases at Hospital for Special Surgery/Weill Cornell Medicine, New York. Her clinical and research focus is on reproductive health issues in individuals with rheumatic disease. Dr. Chan is an assistant professor at Weill Cornell Medical College and an attending physician at Hospital for Special Surgery and Memorial Sloan Kettering Cancer Center in New York. Before moving to New York City, she spent 7 years in private practice in Rhode Island and was a columnist for a monthly rheumatology publication, writing about the challenges of starting life as a full-fledged rheumatologist in a private practice. Follow Dr Chan on Twitter. Dr. Siegel and Dr. Chan disclosed no relevant financial relationships.

A version of this article – an editorial collaboration between Medscape and the Hospital for Special Surgery – first appeared on Medscape.com.

The field of “reproductive rheumatology” has received growing attention in recent years as we learn more about how autoimmune rheumatic diseases and their treatment affect women of reproductive age. In 2020, the American College of Rheumatology published a comprehensive guideline that includes recommendations and supporting evidence for managing issues related to reproductive health in patients with rheumatic diseases and has since launched an ongoing Reproductive Health Initiative, with the goal of translating established guidelines into practice through various education and awareness campaigns. One area addressed by the guideline that comes up commonly in practice but receives less attention and research is the use of assisted reproductive technology (ART) in patients with rheumatic diseases.

Literature is conflicting regarding whether patients with autoimmune rheumatic diseases are inherently at increased risk for infertility, defined as failure to achieve a clinical pregnancy after 12 months or more of regular unprotected intercourse, or subfertility, defined as a delay in conception. Regardless, several factors indirectly contribute to a disproportionate risk for infertility or subfertility in this patient population, including active inflammatory disease, reduced ovarian reserve, and medications.

Patients with subfertility or infertility who desire pregnancy may pursue ovulation induction with timed intercourse or intrauterine insemination, in vitro fertilization (IVF)/intracytoplasmic sperm injection with either embryo transfer, or gestational surrogacy. Those who require treatment with cyclophosphamide or who plan to defer pregnancy for whatever reason can opt for oocyte cryopreservation (colloquially known as “egg freezing”). For IVF and oocyte cryopreservation, controlled ovarian stimulation is typically the first step (except in unstimulated, or “natural cycle,” IVF).

Various protocols are used for ovarian stimulation and ovulation induction, the nuances of which are beyond the scope of this article. In general, ovarian stimulation involves gonadotropin therapy (follicle-stimulating hormone and/or human menopausal gonadotropin) administered via scheduled subcutaneous injections to stimulate follicular growth, as well as gonadotropin-releasing hormone (GnRH) agonists or antagonists to suppress luteinizing hormone, preventing ovulation. Adjunctive oral therapy (clomiphene citrate or letrozole, an aromatase inhibitor) may be used as well. The patient has frequent lab monitoring of hormone levels and transvaginal ultrasounds to measure follicle number and size and, when the timing is right, receives an “ovulation trigger” – either human chorionic gonadotropin or GnRH agonist, depending on the protocol. At this point, transvaginal ultrasound–guided egg retrieval is done under sedation. Recovered oocytes are then either frozen for later use or fertilized in the lab for embryo transfer. Lastly, exogenous hormones are often used: estrogen to support frozen embryo transfers and progesterone for so-called luteal phase support.

ART is not contraindicated in patients with autoimmune rheumatic diseases, but there may be additional factors to consider, particularly for those with systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and antiphospholipid antibodies (aPL) without clinical APS.

Ovarian stimulation elevates estrogen levels to varying degrees depending on the patient and the medications used. In all cases, though, peak levels are significantly lower than levels reached during pregnancy. It is well established that elevated estrogen – whether from hormone therapies or pregnancy – significantly increases thrombotic risk, even in healthy people. High-risk patients should receive low-molecular-weight heparin – a prophylactic dose for patients with either positive aPL without clinical APS (including those with SLE) or with obstetric APS, and a therapeutic dose for those with thrombotic APS – during ART procedures.

In patients with SLE, another concern is that increased estrogen will cause disease flare. One case series published in 2017 reported 37 patients with SLE and/or APS who underwent 97 IVF cycles, of which 8% were complicated by flare or thrombotic events. Notably, half of these complications occurred in patients who stopped prescribed therapies (immunomodulatory therapy in two patients with SLE, anticoagulation in two patients with APS) after failure to conceive. In a separate study from 2000 including 19 patients with SLE, APS, or high-titer aPL who underwent 68 IVF cycles, 19% of cycles in patients with SLE were complicated by flare, and no thrombotic events occurred in the cohort. The authors concluded that ovulation induction does not exacerbate SLE or APS. In these studies, the overall pregnancy rates were felt to be consistent with those achieved by the general population through IVF. Although obstetric complications, such as preeclampsia and preterm delivery, were reported in about half of the pregnancies described, these are known to occur more frequently in those with SLE and APS, especially when active disease or other risk factors are present. There are no large-scale, controlled studies evaluating ART outcomes in patients with autoimmune rheumatic diseases to date.

Finally, ovarian hyperstimulation syndrome (OHSS) is an increasingly rare but severe complication of ovarian stimulation. OHSS is characterized by capillary leak, fluid overload, and cytokine release syndrome and can lead to thromboembolic events. Comorbidities like hypertension and renal failure, which can go along with autoimmune rheumatic diseases, are risk factors for OHSS. The use of human chorionic gonadotropin to trigger ovulation is also associated with an increased risk for OHSS, so a GnRH agonist trigger may be preferable.

The ACR guideline recommends that individuals with any of these underlying conditions undergo ART only in expert centers. The ovarian stimulation protocol needs to be tailored to the individual patient to minimize risk and optimize outcomes. The overall goal when managing patients with autoimmune rheumatic diseases during ART is to establish and maintain disease control with pregnancy-compatible medications (when pregnancy is the goal). With adequate planning, appropriate treatment, and collaboration between obstetricians and rheumatologists, individuals with autoimmune rheumatic diseases can safely pursue ART and go on to have successful pregnancies.

Dr. Siegel is a 2022-2023 UCB Women’s Health rheumatology fellow in the rheumatology reproductive health program of the Barbara Volcker Center for Women and Rheumatic Diseases at Hospital for Special Surgery/Weill Cornell Medicine, New York. Her clinical and research focus is on reproductive health issues in individuals with rheumatic disease. Dr. Chan is an assistant professor at Weill Cornell Medical College and an attending physician at Hospital for Special Surgery and Memorial Sloan Kettering Cancer Center in New York. Before moving to New York City, she spent 7 years in private practice in Rhode Island and was a columnist for a monthly rheumatology publication, writing about the challenges of starting life as a full-fledged rheumatologist in a private practice. Follow Dr Chan on Twitter. Dr. Siegel and Dr. Chan disclosed no relevant financial relationships.

A version of this article – an editorial collaboration between Medscape and the Hospital for Special Surgery – first appeared on Medscape.com.

Patients with the systemic sclerosis subtype of pulmonary arterial hypertension showed a distinctive bioactive metabolic profile associated with more severe disease than other subgroups, based on data from approximately 1,500 individuals.

The overall prognosis and therapeutic response for patients with pulmonary arterial hypertension associated with systemic sclerosis (SSc-PAH) tends to be worse than for patients with other types of PAH, such as idiopathic pulmonary arterial hypertension (IPAH), but the impact of different metabolite profiles among subtypes of disease has not been explored, wrote Mona Alotaibi, MD, of the University of California, San Diego, and colleagues.

“Recently, metabolic dysregulation has been proposed as a key mechanism by which IPAH and SSc-PAH differ and could control such disparities,” they noted. Clarifying the molecular mechanisms of SSc-PAH could inform management and treatment, they added.

In a study published in the journal Chest, the researchers sought to identify a bioactive lipid signature unique to SSc-PAH. They identified 400 patients with SSc-PAH and 1,082 with IPAH. An additional 100 patients with scleroderma but no PH and 44 patients with scleroderma who had PH were included for external validation. The mean ages of the patients with IPAH and SSc-PAH in the discovery and validation cohorts ranged from approximately 51 to 65 years; more than 75% of patients across the groups were women.

The researchers tested more than 700 bioactive lipid metabolites using liquid chromatography/mass spectrometry. They found five metabolites that distinguished SSc-PAH and IPAH that were significantly associated with markers of disease severity: 17-beta estradiol, novel Eic, nervonic acid, fatty acid esters of hydroxy fatty acids, and prostaglandin F2 alpha (PGF 2 alpha).

The biomarkers were increased in SSc-PAH patients compared to patients with SSC alone, which suggests that the biomarkers are related to PAH and not to scleroderma alone, the researchers noted.

In particular, nervonic acid was associated with worse functional capacity, in SSc-PAH patients, as were higher levels of 17-beta estradiol and prostaglandin F2 alpha. Also, 17-beta estradiol was associated with lower cardiac impairment (CI) and stroke volume index (SVI) in SSc-PAH patients, but higher SVI in IPAH patients. PGF 2 alpha was associated with lower CI and SVI and higher pulmonary vascular resistance in SSc-PAH and IPAH combined.

The study findings were limited by several factors including the inability to adjust for all potential confounders between IPAH and SSc-PAH, and the fact that a clear causal relationship could not be determined, the researchers noted. Inadequate statistical power to analyze SSc-PAH data was another limitation, and studies with detailed scleroderma phenotypes are needed to validate the results, they said.

However, the current study provides insight on the metabolic differences in SSc-PAH and the potential impact on disease pathology that may inform diagnosis, prognosis, and treatment strategies for SSc-PAH patients, they concluded.

The study was supported by the National Institutes of Health. Several individual investigators received support from organizations including the American Heart Association and the Chest Foundation, and from companies including Livanova, Equillium, Corvus, Bayer, and Actelion, but the authors had no relevant financial conflicts to disclose.

Patients with the systemic sclerosis subtype of pulmonary arterial hypertension showed a distinctive bioactive metabolic profile associated with more severe disease than other subgroups, based on data from approximately 1,500 individuals.

The overall prognosis and therapeutic response for patients with pulmonary arterial hypertension associated with systemic sclerosis (SSc-PAH) tends to be worse than for patients with other types of PAH, such as idiopathic pulmonary arterial hypertension (IPAH), but the impact of different metabolite profiles among subtypes of disease has not been explored, wrote Mona Alotaibi, MD, of the University of California, San Diego, and colleagues.

“Recently, metabolic dysregulation has been proposed as a key mechanism by which IPAH and SSc-PAH differ and could control such disparities,” they noted. Clarifying the molecular mechanisms of SSc-PAH could inform management and treatment, they added.

In a study published in the journal Chest, the researchers sought to identify a bioactive lipid signature unique to SSc-PAH. They identified 400 patients with SSc-PAH and 1,082 with IPAH. An additional 100 patients with scleroderma but no PH and 44 patients with scleroderma who had PH were included for external validation. The mean ages of the patients with IPAH and SSc-PAH in the discovery and validation cohorts ranged from approximately 51 to 65 years; more than 75% of patients across the groups were women.

The researchers tested more than 700 bioactive lipid metabolites using liquid chromatography/mass spectrometry. They found five metabolites that distinguished SSc-PAH and IPAH that were significantly associated with markers of disease severity: 17-beta estradiol, novel Eic, nervonic acid, fatty acid esters of hydroxy fatty acids, and prostaglandin F2 alpha (PGF 2 alpha).

The biomarkers were increased in SSc-PAH patients compared to patients with SSC alone, which suggests that the biomarkers are related to PAH and not to scleroderma alone, the researchers noted.

In particular, nervonic acid was associated with worse functional capacity, in SSc-PAH patients, as were higher levels of 17-beta estradiol and prostaglandin F2 alpha. Also, 17-beta estradiol was associated with lower cardiac impairment (CI) and stroke volume index (SVI) in SSc-PAH patients, but higher SVI in IPAH patients. PGF 2 alpha was associated with lower CI and SVI and higher pulmonary vascular resistance in SSc-PAH and IPAH combined.

The study findings were limited by several factors including the inability to adjust for all potential confounders between IPAH and SSc-PAH, and the fact that a clear causal relationship could not be determined, the researchers noted. Inadequate statistical power to analyze SSc-PAH data was another limitation, and studies with detailed scleroderma phenotypes are needed to validate the results, they said.

However, the current study provides insight on the metabolic differences in SSc-PAH and the potential impact on disease pathology that may inform diagnosis, prognosis, and treatment strategies for SSc-PAH patients, they concluded.

The study was supported by the National Institutes of Health. Several individual investigators received support from organizations including the American Heart Association and the Chest Foundation, and from companies including Livanova, Equillium, Corvus, Bayer, and Actelion, but the authors had no relevant financial conflicts to disclose.

Patients with the systemic sclerosis subtype of pulmonary arterial hypertension showed a distinctive bioactive metabolic profile associated with more severe disease than other subgroups, based on data from approximately 1,500 individuals.

The overall prognosis and therapeutic response for patients with pulmonary arterial hypertension associated with systemic sclerosis (SSc-PAH) tends to be worse than for patients with other types of PAH, such as idiopathic pulmonary arterial hypertension (IPAH), but the impact of different metabolite profiles among subtypes of disease has not been explored, wrote Mona Alotaibi, MD, of the University of California, San Diego, and colleagues.

“Recently, metabolic dysregulation has been proposed as a key mechanism by which IPAH and SSc-PAH differ and could control such disparities,” they noted. Clarifying the molecular mechanisms of SSc-PAH could inform management and treatment, they added.

In a study published in the journal Chest, the researchers sought to identify a bioactive lipid signature unique to SSc-PAH. They identified 400 patients with SSc-PAH and 1,082 with IPAH. An additional 100 patients with scleroderma but no PH and 44 patients with scleroderma who had PH were included for external validation. The mean ages of the patients with IPAH and SSc-PAH in the discovery and validation cohorts ranged from approximately 51 to 65 years; more than 75% of patients across the groups were women.

The researchers tested more than 700 bioactive lipid metabolites using liquid chromatography/mass spectrometry. They found five metabolites that distinguished SSc-PAH and IPAH that were significantly associated with markers of disease severity: 17-beta estradiol, novel Eic, nervonic acid, fatty acid esters of hydroxy fatty acids, and prostaglandin F2 alpha (PGF 2 alpha).

The biomarkers were increased in SSc-PAH patients compared to patients with SSC alone, which suggests that the biomarkers are related to PAH and not to scleroderma alone, the researchers noted.

In particular, nervonic acid was associated with worse functional capacity, in SSc-PAH patients, as were higher levels of 17-beta estradiol and prostaglandin F2 alpha. Also, 17-beta estradiol was associated with lower cardiac impairment (CI) and stroke volume index (SVI) in SSc-PAH patients, but higher SVI in IPAH patients. PGF 2 alpha was associated with lower CI and SVI and higher pulmonary vascular resistance in SSc-PAH and IPAH combined.

The study findings were limited by several factors including the inability to adjust for all potential confounders between IPAH and SSc-PAH, and the fact that a clear causal relationship could not be determined, the researchers noted. Inadequate statistical power to analyze SSc-PAH data was another limitation, and studies with detailed scleroderma phenotypes are needed to validate the results, they said.

However, the current study provides insight on the metabolic differences in SSc-PAH and the potential impact on disease pathology that may inform diagnosis, prognosis, and treatment strategies for SSc-PAH patients, they concluded.

The study was supported by the National Institutes of Health. Several individual investigators received support from organizations including the American Heart Association and the Chest Foundation, and from companies including Livanova, Equillium, Corvus, Bayer, and Actelion, but the authors had no relevant financial conflicts to disclose.

With use of intravenous immunoglobulin for the treatment of adults with dermatomyositis, a significantly higher percentage of patients experienced at least minimal improvement in disease activity in comparison with placebo in the first-ever phase 3 trial of the blood-product therapy for the condition.

Until this trial, published in the New England Journal of Medicine, there had not been an extensive evaluation of IVIG for the treatment of dermatomyositis, the study’s authors noted.

Glucocorticoids are typically offered as first-line therapy, followed by various immunosuppressants. IVIG is composed of purified liquid IgG concentrates from human plasma. It has been prescribed off label as second- or third-line therapy for dermatomyositis, usually along with immunosuppressive drugs. In European guidelines, it has been recommended as a glucocorticoid-sparing agent for patients with this condition.

“The study provides support that IVIG is effective in treating the signs and symptoms of patients with dermatomyositis, at least in the short term,” said David Fiorentino, MD, PhD, professor of dermatology and associate residency program director at Stanford Health Care, Stanford, California, who was not involved in the study.

“IVIG appears to be effective for patients with any severity level and works relatively quickly [within 1 month of therapy],” he added. “IVIG is effective in treating both the muscle symptoms as well as the rash of dermatomyositis, which is important, as both organ systems can cause significant patient morbidity in this disease.”

Time to improvement was shorter with IVIG than with placebo (a median of 35 days vs. 115 days), said Kathryn H. Dao, MD, associate professor in the division of rheumatic diseases at the University of Texas Southwestern Medical Center, Dallas, who was not involved in the study.

The study’s greatest strengths are its international, multicenter, randomized, placebo-controlled design, Dr. Dao said. In addition, “these patients were permitted to be on background medicines that we typically use in real-world situations.”
 

Study methodology

Researchers led by Rohit Aggarwal, MD, of the division of rheumatology and clinical immunology at the University of Pittsburgh, recruited patients aged 18-80 years with active dermatomyositis. Individuals were randomly assigned in a 1:1 ratio to receive either IVIG at a dose of 2.0 g/kg of body weight or placebo (0.9% sodium chloride) every 4 weeks for 16 weeks.

Courtesy RegionalDerm.com

Those who were administered placebo and those who did not experience confirmed clinical deterioration while receiving IVIG could participate in an open-label extension phase for another 24 weeks.

The primary endpoint was a response, defined as a Total Improvement Score (TIS) of at least 20 (indicating at least minimal improvement) at week 16 and no confirmed deterioration up to week 16. The TIS is a weighted composite score that reflects the change in a core set of six measures of myositis activity over time. Scores span from 0 to 100, with higher scores indicating more significant improvement.
 

Secondary endpoints

Key secondary endpoints included moderate improvement (TIS ≥ 40) and major improvement (TIS ≥ 60) and change in score on the Cutaneous Dermatomyositis Disease Area and Severity Index.

A total of 95 patients underwent randomization; 47 patients received IVIG and 48 received placebo. At 16 weeks, a TIS of at least 20 occurred in 37 of 47 (79%) patients who received IVIG and in 21 of 48 (44%) patients with placebo (difference, 35%; 95% confidence interval, 17%-53%; P < .001).

The results with respect to the secondary endpoints, including at least moderate improvement and major improvement, were generally in the same direction as the results of the primary endpoint analysis, except for change in creatine kinase (CK) level (an individual core measure of the TIS), which did not differ meaningfully between the two groups.

Adverse events

Over the course of 40 weeks, 282 treatment-related adverse events were documented among patients who received IVIG. Headache was experienced by 42%, pyrexia by 19%, and nausea by 16%. Nine serious adverse events occurred and were believed to be associated with IVIG, including six thromboembolic events.

Despite the favorable outcome observed with IVIG, in an editorial that accompanied the study, Anthony A. Amato, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, noted that “most of the core components of the TIS are subjective. Because of the high percentage of patients who had a response with placebo, large numbers of patients will be needed in future trials to show a significant difference between trial groups, or the primary endpoint would need to be set higher (e.g., a TIS of ≥40).”

Dr. Dao thought it was significant that the study proactively assessed patients for venous thrombotic events (VTEs) after each infusion. There were eight events in six patients who received IVIG. “Of interest and possibly practice changing is the finding that slowing the IVIG infusion rate from 0.12 to 0.04 mL/kg per minute reduced the incidence of VTEs from 1.54/100 patient-months to 0.54/100 patient-months,” she said. “This is important, as it informs clinicians that IVIG infusion rates should be slower for patients with active dermatomyositis to reduce the risk for blood clots.”
 

Study weaknesses

A considerable proportion of patients with dermatomyositis do not have clinical muscle involvement but do have rash and do not substantially differ in any other ways from those with classic dermatomyositis, Dr. Fiorentino said.

“These patients were not eligible to enter the trial, and so we have no data on the efficacy of IVIG in this population,” he said. “Unfortunately, these patients might now be denied insurance reimbursement for IVIG therapy, given that they are not part of the indicated patient population in the label.”

In addition, there is limited information about Black, Asian, or Hispanic patients because few of those patients participated in the study. That is also the case for patients younger than 18, which for this disease is relevant because incidence peaks in younger patients (juvenile dermatomyositis), Dr. Fiorentino noted.

Among the study’s weaknesses, Dr. Dao noted that more than 70% of participants were women. The study was short in duration, fewer than half of patients underwent muscle biopsy to confirm myositis, and only two thirds of patients underwent electromyography/nerve conduction studies to show evidence of myositis. There was a high placebo response (44%), the CK values were not high at the start of the trial, and they did not change with treatment.

No analysis was performed to evaluate the efficacy of IVIG across dermatomyositis subgroups – defined by autoantibodies – but the study likely was not powered to do so. These subgroups might respond differently to IVIG, yielding important information, Fiorentino said.

The study provided efficacy data for only one formulation of IVIG, Octagam 10%, which was approved for dermatomyositis by the Food and Drug Administration in 2021 on the basis of this trial. However, in the United States, patients with dermatomyositis are treated with multiple brands of IVIG. “The decision around IVIG brand is largely determined by third-party payers, and for the most part, the different brands are used interchangeably from the standpoint of the treating provider,” Dr. Fiorentino said. “This will likely continue to be the case, as the results of this study are generally being extrapolated to all brands of IVIG.”

Multiple IVIG brands that have been used for immune-mediated diseases differ in concentration, content of IgA, sugar concentration, additives, and preparations (for example, the need for reconstitution vs. being ready to use), Dr. Dao said. Octagam 10% is the only brand approved by the FDA for adult dermatomyositis; hence, cost can be an issue for patients if other brands are used off label. The typical cost of IVIG is $100-$400 per gram; a typical course of treatment is estimated to be $30,000-$40,000 per month. “However, if Octagam is not available or a patient has a reaction to it, clinicians may use other IVIG brands as deemed medically necessary to treat their patients,” she said.

Dr. Aggarwal has financial relationships with more than 15 pharmaceutical companies, including Octapharma, which provided financial support for this trial. Some of the coauthors were employees of Octapharma or had financial relationships with the company. Dr. Dao disclosed no relevant financial relationships. Dr. Fiorentino has conducted sponsored research for Pfizer and Argenyx, has received research funding from Serono, and is a paid adviser to Bristol-Myers Squibb, Janssen, Acelyrin, and Corbus.

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

With use of intravenous immunoglobulin for the treatment of adults with dermatomyositis, a significantly higher percentage of patients experienced at least minimal improvement in disease activity in comparison with placebo in the first-ever phase 3 trial of the blood-product therapy for the condition.

Until this trial, published in the New England Journal of Medicine, there had not been an extensive evaluation of IVIG for the treatment of dermatomyositis, the study’s authors noted.

Glucocorticoids are typically offered as first-line therapy, followed by various immunosuppressants. IVIG is composed of purified liquid IgG concentrates from human plasma. It has been prescribed off label as second- or third-line therapy for dermatomyositis, usually along with immunosuppressive drugs. In European guidelines, it has been recommended as a glucocorticoid-sparing agent for patients with this condition.

“The study provides support that IVIG is effective in treating the signs and symptoms of patients with dermatomyositis, at least in the short term,” said David Fiorentino, MD, PhD, professor of dermatology and associate residency program director at Stanford Health Care, Stanford, California, who was not involved in the study.

“IVIG appears to be effective for patients with any severity level and works relatively quickly [within 1 month of therapy],” he added. “IVIG is effective in treating both the muscle symptoms as well as the rash of dermatomyositis, which is important, as both organ systems can cause significant patient morbidity in this disease.”

Time to improvement was shorter with IVIG than with placebo (a median of 35 days vs. 115 days), said Kathryn H. Dao, MD, associate professor in the division of rheumatic diseases at the University of Texas Southwestern Medical Center, Dallas, who was not involved in the study.

The study’s greatest strengths are its international, multicenter, randomized, placebo-controlled design, Dr. Dao said. In addition, “these patients were permitted to be on background medicines that we typically use in real-world situations.”
 

Study methodology

Researchers led by Rohit Aggarwal, MD, of the division of rheumatology and clinical immunology at the University of Pittsburgh, recruited patients aged 18-80 years with active dermatomyositis. Individuals were randomly assigned in a 1:1 ratio to receive either IVIG at a dose of 2.0 g/kg of body weight or placebo (0.9% sodium chloride) every 4 weeks for 16 weeks.

Courtesy RegionalDerm.com

Those who were administered placebo and those who did not experience confirmed clinical deterioration while receiving IVIG could participate in an open-label extension phase for another 24 weeks.

The primary endpoint was a response, defined as a Total Improvement Score (TIS) of at least 20 (indicating at least minimal improvement) at week 16 and no confirmed deterioration up to week 16. The TIS is a weighted composite score that reflects the change in a core set of six measures of myositis activity over time. Scores span from 0 to 100, with higher scores indicating more significant improvement.
 

Secondary endpoints

Key secondary endpoints included moderate improvement (TIS ≥ 40) and major improvement (TIS ≥ 60) and change in score on the Cutaneous Dermatomyositis Disease Area and Severity Index.

A total of 95 patients underwent randomization; 47 patients received IVIG and 48 received placebo. At 16 weeks, a TIS of at least 20 occurred in 37 of 47 (79%) patients who received IVIG and in 21 of 48 (44%) patients with placebo (difference, 35%; 95% confidence interval, 17%-53%; P < .001).

The results with respect to the secondary endpoints, including at least moderate improvement and major improvement, were generally in the same direction as the results of the primary endpoint analysis, except for change in creatine kinase (CK) level (an individual core measure of the TIS), which did not differ meaningfully between the two groups.

Adverse events

Over the course of 40 weeks, 282 treatment-related adverse events were documented among patients who received IVIG. Headache was experienced by 42%, pyrexia by 19%, and nausea by 16%. Nine serious adverse events occurred and were believed to be associated with IVIG, including six thromboembolic events.

Despite the favorable outcome observed with IVIG, in an editorial that accompanied the study, Anthony A. Amato, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, noted that “most of the core components of the TIS are subjective. Because of the high percentage of patients who had a response with placebo, large numbers of patients will be needed in future trials to show a significant difference between trial groups, or the primary endpoint would need to be set higher (e.g., a TIS of ≥40).”

Dr. Dao thought it was significant that the study proactively assessed patients for venous thrombotic events (VTEs) after each infusion. There were eight events in six patients who received IVIG. “Of interest and possibly practice changing is the finding that slowing the IVIG infusion rate from 0.12 to 0.04 mL/kg per minute reduced the incidence of VTEs from 1.54/100 patient-months to 0.54/100 patient-months,” she said. “This is important, as it informs clinicians that IVIG infusion rates should be slower for patients with active dermatomyositis to reduce the risk for blood clots.”
 

Study weaknesses

A considerable proportion of patients with dermatomyositis do not have clinical muscle involvement but do have rash and do not substantially differ in any other ways from those with classic dermatomyositis, Dr. Fiorentino said.

“These patients were not eligible to enter the trial, and so we have no data on the efficacy of IVIG in this population,” he said. “Unfortunately, these patients might now be denied insurance reimbursement for IVIG therapy, given that they are not part of the indicated patient population in the label.”

In addition, there is limited information about Black, Asian, or Hispanic patients because few of those patients participated in the study. That is also the case for patients younger than 18, which for this disease is relevant because incidence peaks in younger patients (juvenile dermatomyositis), Dr. Fiorentino noted.

Among the study’s weaknesses, Dr. Dao noted that more than 70% of participants were women. The study was short in duration, fewer than half of patients underwent muscle biopsy to confirm myositis, and only two thirds of patients underwent electromyography/nerve conduction studies to show evidence of myositis. There was a high placebo response (44%), the CK values were not high at the start of the trial, and they did not change with treatment.

No analysis was performed to evaluate the efficacy of IVIG across dermatomyositis subgroups – defined by autoantibodies – but the study likely was not powered to do so. These subgroups might respond differently to IVIG, yielding important information, Fiorentino said.

The study provided efficacy data for only one formulation of IVIG, Octagam 10%, which was approved for dermatomyositis by the Food and Drug Administration in 2021 on the basis of this trial. However, in the United States, patients with dermatomyositis are treated with multiple brands of IVIG. “The decision around IVIG brand is largely determined by third-party payers, and for the most part, the different brands are used interchangeably from the standpoint of the treating provider,” Dr. Fiorentino said. “This will likely continue to be the case, as the results of this study are generally being extrapolated to all brands of IVIG.”

Multiple IVIG brands that have been used for immune-mediated diseases differ in concentration, content of IgA, sugar concentration, additives, and preparations (for example, the need for reconstitution vs. being ready to use), Dr. Dao said. Octagam 10% is the only brand approved by the FDA for adult dermatomyositis; hence, cost can be an issue for patients if other brands are used off label. The typical cost of IVIG is $100-$400 per gram; a typical course of treatment is estimated to be $30,000-$40,000 per month. “However, if Octagam is not available or a patient has a reaction to it, clinicians may use other IVIG brands as deemed medically necessary to treat their patients,” she said.

Dr. Aggarwal has financial relationships with more than 15 pharmaceutical companies, including Octapharma, which provided financial support for this trial. Some of the coauthors were employees of Octapharma or had financial relationships with the company. Dr. Dao disclosed no relevant financial relationships. Dr. Fiorentino has conducted sponsored research for Pfizer and Argenyx, has received research funding from Serono, and is a paid adviser to Bristol-Myers Squibb, Janssen, Acelyrin, and Corbus.

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

With use of intravenous immunoglobulin for the treatment of adults with dermatomyositis, a significantly higher percentage of patients experienced at least minimal improvement in disease activity in comparison with placebo in the first-ever phase 3 trial of the blood-product therapy for the condition.

Until this trial, published in the New England Journal of Medicine, there had not been an extensive evaluation of IVIG for the treatment of dermatomyositis, the study’s authors noted.

Glucocorticoids are typically offered as first-line therapy, followed by various immunosuppressants. IVIG is composed of purified liquid IgG concentrates from human plasma. It has been prescribed off label as second- or third-line therapy for dermatomyositis, usually along with immunosuppressive drugs. In European guidelines, it has been recommended as a glucocorticoid-sparing agent for patients with this condition.

“The study provides support that IVIG is effective in treating the signs and symptoms of patients with dermatomyositis, at least in the short term,” said David Fiorentino, MD, PhD, professor of dermatology and associate residency program director at Stanford Health Care, Stanford, California, who was not involved in the study.

“IVIG appears to be effective for patients with any severity level and works relatively quickly [within 1 month of therapy],” he added. “IVIG is effective in treating both the muscle symptoms as well as the rash of dermatomyositis, which is important, as both organ systems can cause significant patient morbidity in this disease.”

Time to improvement was shorter with IVIG than with placebo (a median of 35 days vs. 115 days), said Kathryn H. Dao, MD, associate professor in the division of rheumatic diseases at the University of Texas Southwestern Medical Center, Dallas, who was not involved in the study.

The study’s greatest strengths are its international, multicenter, randomized, placebo-controlled design, Dr. Dao said. In addition, “these patients were permitted to be on background medicines that we typically use in real-world situations.”
 

Study methodology

Researchers led by Rohit Aggarwal, MD, of the division of rheumatology and clinical immunology at the University of Pittsburgh, recruited patients aged 18-80 years with active dermatomyositis. Individuals were randomly assigned in a 1:1 ratio to receive either IVIG at a dose of 2.0 g/kg of body weight or placebo (0.9% sodium chloride) every 4 weeks for 16 weeks.

Courtesy RegionalDerm.com

Those who were administered placebo and those who did not experience confirmed clinical deterioration while receiving IVIG could participate in an open-label extension phase for another 24 weeks.

The primary endpoint was a response, defined as a Total Improvement Score (TIS) of at least 20 (indicating at least minimal improvement) at week 16 and no confirmed deterioration up to week 16. The TIS is a weighted composite score that reflects the change in a core set of six measures of myositis activity over time. Scores span from 0 to 100, with higher scores indicating more significant improvement.
 

Secondary endpoints

Key secondary endpoints included moderate improvement (TIS ≥ 40) and major improvement (TIS ≥ 60) and change in score on the Cutaneous Dermatomyositis Disease Area and Severity Index.

A total of 95 patients underwent randomization; 47 patients received IVIG and 48 received placebo. At 16 weeks, a TIS of at least 20 occurred in 37 of 47 (79%) patients who received IVIG and in 21 of 48 (44%) patients with placebo (difference, 35%; 95% confidence interval, 17%-53%; P < .001).

The results with respect to the secondary endpoints, including at least moderate improvement and major improvement, were generally in the same direction as the results of the primary endpoint analysis, except for change in creatine kinase (CK) level (an individual core measure of the TIS), which did not differ meaningfully between the two groups.

Adverse events

Over the course of 40 weeks, 282 treatment-related adverse events were documented among patients who received IVIG. Headache was experienced by 42%, pyrexia by 19%, and nausea by 16%. Nine serious adverse events occurred and were believed to be associated with IVIG, including six thromboembolic events.

Despite the favorable outcome observed with IVIG, in an editorial that accompanied the study, Anthony A. Amato, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, noted that “most of the core components of the TIS are subjective. Because of the high percentage of patients who had a response with placebo, large numbers of patients will be needed in future trials to show a significant difference between trial groups, or the primary endpoint would need to be set higher (e.g., a TIS of ≥40).”

Dr. Dao thought it was significant that the study proactively assessed patients for venous thrombotic events (VTEs) after each infusion. There were eight events in six patients who received IVIG. “Of interest and possibly practice changing is the finding that slowing the IVIG infusion rate from 0.12 to 0.04 mL/kg per minute reduced the incidence of VTEs from 1.54/100 patient-months to 0.54/100 patient-months,” she said. “This is important, as it informs clinicians that IVIG infusion rates should be slower for patients with active dermatomyositis to reduce the risk for blood clots.”
 

Study weaknesses

A considerable proportion of patients with dermatomyositis do not have clinical muscle involvement but do have rash and do not substantially differ in any other ways from those with classic dermatomyositis, Dr. Fiorentino said.

“These patients were not eligible to enter the trial, and so we have no data on the efficacy of IVIG in this population,” he said. “Unfortunately, these patients might now be denied insurance reimbursement for IVIG therapy, given that they are not part of the indicated patient population in the label.”

In addition, there is limited information about Black, Asian, or Hispanic patients because few of those patients participated in the study. That is also the case for patients younger than 18, which for this disease is relevant because incidence peaks in younger patients (juvenile dermatomyositis), Dr. Fiorentino noted.

Among the study’s weaknesses, Dr. Dao noted that more than 70% of participants were women. The study was short in duration, fewer than half of patients underwent muscle biopsy to confirm myositis, and only two thirds of patients underwent electromyography/nerve conduction studies to show evidence of myositis. There was a high placebo response (44%), the CK values were not high at the start of the trial, and they did not change with treatment.

No analysis was performed to evaluate the efficacy of IVIG across dermatomyositis subgroups – defined by autoantibodies – but the study likely was not powered to do so. These subgroups might respond differently to IVIG, yielding important information, Fiorentino said.

The study provided efficacy data for only one formulation of IVIG, Octagam 10%, which was approved for dermatomyositis by the Food and Drug Administration in 2021 on the basis of this trial. However, in the United States, patients with dermatomyositis are treated with multiple brands of IVIG. “The decision around IVIG brand is largely determined by third-party payers, and for the most part, the different brands are used interchangeably from the standpoint of the treating provider,” Dr. Fiorentino said. “This will likely continue to be the case, as the results of this study are generally being extrapolated to all brands of IVIG.”

Multiple IVIG brands that have been used for immune-mediated diseases differ in concentration, content of IgA, sugar concentration, additives, and preparations (for example, the need for reconstitution vs. being ready to use), Dr. Dao said. Octagam 10% is the only brand approved by the FDA for adult dermatomyositis; hence, cost can be an issue for patients if other brands are used off label. The typical cost of IVIG is $100-$400 per gram; a typical course of treatment is estimated to be $30,000-$40,000 per month. “However, if Octagam is not available or a patient has a reaction to it, clinicians may use other IVIG brands as deemed medically necessary to treat their patients,” she said.

Dr. Aggarwal has financial relationships with more than 15 pharmaceutical companies, including Octapharma, which provided financial support for this trial. Some of the coauthors were employees of Octapharma or had financial relationships with the company. Dr. Dao disclosed no relevant financial relationships. Dr. Fiorentino has conducted sponsored research for Pfizer and Argenyx, has received research funding from Serono, and is a paid adviser to Bristol-Myers Squibb, Janssen, Acelyrin, and Corbus.

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

Tixagevimab copackaged with cilgavimab (Evusheld) is a safe and effective preexposure prophylaxis (PrEP) in patients undergoing B-cell-depleting therapies who have poor immune response to COVID-19 vaccination and are at high risk for serious COVID-19 illness, a small, single-site study suggests.

Evusheld, the only COVID-19 PrEP option available, has Emergency Use Authorization (EUA) from the Food and Drug Administration for treatment of immunocompromised patients who may not respond sufficiently to COVID-19 vaccination and patients who’ve had a severe adverse reaction to COVID-19 vaccination.

“We report the largest real-world experience of Evusheld in this population, and our findings are encouraging,” lead study author Cassandra Calabrese, DO, rheumatologist and infectious disease specialist at Cleveland Clinic, said in an interview.

“Of 412 patients who received Evusheld, 12 [2.9%] developed breakthrough COVID-19, with 11 having mild courses and 1 who required hospitalization but recovered,” she added.

“Our data suggest that Evusheld PrEP, in combination with aggressive outpatient treatment of COVID-19, is likely effective in lowering risk of severe COVID in this vulnerable group.

“Practitioners who care for patients with immune-mediated inflammatory diseases should triage high-risk patients for Evusheld as well as rapid diagnosis and aggressive outpatient therapy if infected,” Dr. Calabrese advised.

For the study, Dr. Calabrese and colleagues at Cleveland Clinic searched the health care system pharmacy records for patients with immune‐mediated inflammatory diseases (IMIDs) or inborn errors of humoral immunity (IEI) who met the criteria to receive Evusheld. The researchers included patients on B-cell-depleting therapies or with humoral IEI who had received at least one dose of Evusheld and were later diagnosed with COVID-19, and they excluded those treated with B-cell-depleting therapies for cancer.
 

EVUSHELD was well tolerated

After extracting data on COVID-19 infection, vaccination status, and outcomes, they found that, between Jan. 18 and May 28, 2022, 412 patients with IMIDs or humoral IEI received Evusheld. No deaths occurred among these patients and, overall, they tolerated the medication well.

All 12 patients who experienced breakthrough COVID-19 infection were treated with B-cell-depleting therapies. Among the 12 patients:

• Six patients developed infection 13-84 (median 19) days after receiving 150 mg/150 mg tixagevimab/cilgavimab.
• Six patients developed infection 19-72 (median of 38.5) days after either a single dose of 300 mg/300 mg or a second dose of 150 mg/150 mg.
• Eleven patients had mild illness and recovered at home; one patient was hospitalized and treated with high-flow oxygen. All cases had been vaccinated against COVID-19 (five received two vaccinations, six received three, and one received four).
• One possible serious adverse event involved a patient with COVID-19 and immune-mediated thrombocytopenia (ITP) who was hospitalized soon after receiving Evusheld with ITP flare that resolved with intravenous immunoglobulin.

Dr. Calabrese acknowledged limitations to the study, including few patients, lack of a comparator group, and the study period falling during the Omicron wave.

“Also, nine of the breakthrough cases received additional COVID-19 therapy (oral antiviral or monoclonal antibody), which falls within standard of care for this high-risk group but prevents ascribing effectiveness to individual components of the regimen,” she added.

“Evusheld is authorized for PrEP against COVID-19 in patients at high risk for severe COVID due to suboptimal vaccine responses. This includes patients receiving B-cell-depleting drugs like rituximab, and patients with inborn errors of humoral immunity,” Dr. Calabrese explained.

“It is well known that this group of patients is at very high risk for severe COVID and death, even when fully vaccinated, and it has become clear that more strategies are needed to protect this vulnerable group, including use of Evusheld as well as aggressive treatment if infected,” she added.  
 

Evusheld not always easy to obtain

Although the medication has been available in the United States since January 2022, Dr. Calabrese said, patients may not receive it because of barriers including lack of both awareness and access.

Davey Smith, MD, professor of medicine and head of infectious diseases and global public health at the University of California San Diego, in La Jolla, said in an interview that he was not surprised by the results, but added that the study was conducted in too few patients to draw any strong conclusions or affect patient care.

“This small study that showed that breakthrough infections occurred but were generally mild, provides a small glimpse of real-world use of tixagevimab/cilgavimab as PrEP for immunocompromised persons,” said Dr. Smith, who was not involved in the study.

“In the setting of Omicron and vaccination, I would expect the same outcomes reported even without the treatment,” he added.

Dr. Smith recommends larger related randomized, controlled trials to provide clinicians with sufficient data to guide them in their patient care.

Graham Snyder, MD, associate professor in the division of infectious diseases at the University of Pittsburgh and medical director of infection prevention and hospital epidemiology at the University of Pittsburgh Medical Center, noted that the study “adds to a quickly growing literature on the real-world benefits of tixagevimab/cilgavimab to protect vulnerable individuals with weakened immune systems from the complications of COVID-19.

“This study provides a modest addition to our understanding of the role and benefit of Evusheld,” Dr. Snyder said in an interview. “By characterizing only patients who have received Evusheld without an untreated comparison group, we can’t draw any inference about the extent of benefit the agent provided to these patients.

“Substantial data already show that this agent is effective in preventing complications of COVID-19 infection in immunocompromised individuals,” added Dr. Snyder, who was not involved in the study.

“ ‘Immunocompromised’ represents a very diverse set of clinical conditions,” he said. “The research agenda should therefore focus on a more refined description of the effect in specific populations and a continued understanding of the effect of Evusheld in the context of updated vaccination strategies and changing virus ecology.”

Dr. Calabrese and her colleagues wrote that larger, controlled trials are underway.

 

FDA: Evusheld may not neutralize certain SARS-CoV-2 variants

“The biggest unanswered question is how Evusheld will hold up against new variants,” Dr. Calabrese said.

In an Oct. 3, 2022, update, the Food and Drug Administration released a statement about the risk of developing COVID-19 from SARS-CoV-2 variants that are not neutralized by Evusheld. The statement mentions an updated fact sheet that describes reduced protection from Evusheld against the Omicron subvariant BA.4.6, which accounted for nearly 13% of all new COVID-19 cases in the United States in the week ending Oct. 1.

There was no outside funding for the study. Dr. Smith reported no relevant financial conflicts of interest. Dr. Snyder said he is an unpaid adviser to an AstraZeneca observational study that’s assessing the real-world effectiveness of Evusheld.

Tixagevimab copackaged with cilgavimab (Evusheld) is a safe and effective preexposure prophylaxis (PrEP) in patients undergoing B-cell-depleting therapies who have poor immune response to COVID-19 vaccination and are at high risk for serious COVID-19 illness, a small, single-site study suggests.

Evusheld, the only COVID-19 PrEP option available, has Emergency Use Authorization (EUA) from the Food and Drug Administration for treatment of immunocompromised patients who may not respond sufficiently to COVID-19 vaccination and patients who’ve had a severe adverse reaction to COVID-19 vaccination.

“We report the largest real-world experience of Evusheld in this population, and our findings are encouraging,” lead study author Cassandra Calabrese, DO, rheumatologist and infectious disease specialist at Cleveland Clinic, said in an interview.

“Of 412 patients who received Evusheld, 12 [2.9%] developed breakthrough COVID-19, with 11 having mild courses and 1 who required hospitalization but recovered,” she added.

“Our data suggest that Evusheld PrEP, in combination with aggressive outpatient treatment of COVID-19, is likely effective in lowering risk of severe COVID in this vulnerable group.

“Practitioners who care for patients with immune-mediated inflammatory diseases should triage high-risk patients for Evusheld as well as rapid diagnosis and aggressive outpatient therapy if infected,” Dr. Calabrese advised.

For the study, Dr. Calabrese and colleagues at Cleveland Clinic searched the health care system pharmacy records for patients with immune‐mediated inflammatory diseases (IMIDs) or inborn errors of humoral immunity (IEI) who met the criteria to receive Evusheld. The researchers included patients on B-cell-depleting therapies or with humoral IEI who had received at least one dose of Evusheld and were later diagnosed with COVID-19, and they excluded those treated with B-cell-depleting therapies for cancer.
 

EVUSHELD was well tolerated

After extracting data on COVID-19 infection, vaccination status, and outcomes, they found that, between Jan. 18 and May 28, 2022, 412 patients with IMIDs or humoral IEI received Evusheld. No deaths occurred among these patients and, overall, they tolerated the medication well.

All 12 patients who experienced breakthrough COVID-19 infection were treated with B-cell-depleting therapies. Among the 12 patients:

• Six patients developed infection 13-84 (median 19) days after receiving 150 mg/150 mg tixagevimab/cilgavimab.
• Six patients developed infection 19-72 (median of 38.5) days after either a single dose of 300 mg/300 mg or a second dose of 150 mg/150 mg.
• Eleven patients had mild illness and recovered at home; one patient was hospitalized and treated with high-flow oxygen. All cases had been vaccinated against COVID-19 (five received two vaccinations, six received three, and one received four).
• One possible serious adverse event involved a patient with COVID-19 and immune-mediated thrombocytopenia (ITP) who was hospitalized soon after receiving Evusheld with ITP flare that resolved with intravenous immunoglobulin.

Dr. Calabrese acknowledged limitations to the study, including few patients, lack of a comparator group, and the study period falling during the Omicron wave.

“Also, nine of the breakthrough cases received additional COVID-19 therapy (oral antiviral or monoclonal antibody), which falls within standard of care for this high-risk group but prevents ascribing effectiveness to individual components of the regimen,” she added.

“Evusheld is authorized for PrEP against COVID-19 in patients at high risk for severe COVID due to suboptimal vaccine responses. This includes patients receiving B-cell-depleting drugs like rituximab, and patients with inborn errors of humoral immunity,” Dr. Calabrese explained.

“It is well known that this group of patients is at very high risk for severe COVID and death, even when fully vaccinated, and it has become clear that more strategies are needed to protect this vulnerable group, including use of Evusheld as well as aggressive treatment if infected,” she added.  
 

Evusheld not always easy to obtain

Although the medication has been available in the United States since January 2022, Dr. Calabrese said, patients may not receive it because of barriers including lack of both awareness and access.

Davey Smith, MD, professor of medicine and head of infectious diseases and global public health at the University of California San Diego, in La Jolla, said in an interview that he was not surprised by the results, but added that the study was conducted in too few patients to draw any strong conclusions or affect patient care.

“This small study that showed that breakthrough infections occurred but were generally mild, provides a small glimpse of real-world use of tixagevimab/cilgavimab as PrEP for immunocompromised persons,” said Dr. Smith, who was not involved in the study.

“In the setting of Omicron and vaccination, I would expect the same outcomes reported even without the treatment,” he added.

Dr. Smith recommends larger related randomized, controlled trials to provide clinicians with sufficient data to guide them in their patient care.

Graham Snyder, MD, associate professor in the division of infectious diseases at the University of Pittsburgh and medical director of infection prevention and hospital epidemiology at the University of Pittsburgh Medical Center, noted that the study “adds to a quickly growing literature on the real-world benefits of tixagevimab/cilgavimab to protect vulnerable individuals with weakened immune systems from the complications of COVID-19.

“This study provides a modest addition to our understanding of the role and benefit of Evusheld,” Dr. Snyder said in an interview. “By characterizing only patients who have received Evusheld without an untreated comparison group, we can’t draw any inference about the extent of benefit the agent provided to these patients.

“Substantial data already show that this agent is effective in preventing complications of COVID-19 infection in immunocompromised individuals,” added Dr. Snyder, who was not involved in the study.

“ ‘Immunocompromised’ represents a very diverse set of clinical conditions,” he said. “The research agenda should therefore focus on a more refined description of the effect in specific populations and a continued understanding of the effect of Evusheld in the context of updated vaccination strategies and changing virus ecology.”

Dr. Calabrese and her colleagues wrote that larger, controlled trials are underway.

 

FDA: Evusheld may not neutralize certain SARS-CoV-2 variants

“The biggest unanswered question is how Evusheld will hold up against new variants,” Dr. Calabrese said.

In an Oct. 3, 2022, update, the Food and Drug Administration released a statement about the risk of developing COVID-19 from SARS-CoV-2 variants that are not neutralized by Evusheld. The statement mentions an updated fact sheet that describes reduced protection from Evusheld against the Omicron subvariant BA.4.6, which accounted for nearly 13% of all new COVID-19 cases in the United States in the week ending Oct. 1.

There was no outside funding for the study. Dr. Smith reported no relevant financial conflicts of interest. Dr. Snyder said he is an unpaid adviser to an AstraZeneca observational study that’s assessing the real-world effectiveness of Evusheld.

Tixagevimab copackaged with cilgavimab (Evusheld) is a safe and effective preexposure prophylaxis (PrEP) in patients undergoing B-cell-depleting therapies who have poor immune response to COVID-19 vaccination and are at high risk for serious COVID-19 illness, a small, single-site study suggests.

Evusheld, the only COVID-19 PrEP option available, has Emergency Use Authorization (EUA) from the Food and Drug Administration for treatment of immunocompromised patients who may not respond sufficiently to COVID-19 vaccination and patients who’ve had a severe adverse reaction to COVID-19 vaccination.

“We report the largest real-world experience of Evusheld in this population, and our findings are encouraging,” lead study author Cassandra Calabrese, DO, rheumatologist and infectious disease specialist at Cleveland Clinic, said in an interview.

“Of 412 patients who received Evusheld, 12 [2.9%] developed breakthrough COVID-19, with 11 having mild courses and 1 who required hospitalization but recovered,” she added.

“Our data suggest that Evusheld PrEP, in combination with aggressive outpatient treatment of COVID-19, is likely effective in lowering risk of severe COVID in this vulnerable group.

“Practitioners who care for patients with immune-mediated inflammatory diseases should triage high-risk patients for Evusheld as well as rapid diagnosis and aggressive outpatient therapy if infected,” Dr. Calabrese advised.

For the study, Dr. Calabrese and colleagues at Cleveland Clinic searched the health care system pharmacy records for patients with immune‐mediated inflammatory diseases (IMIDs) or inborn errors of humoral immunity (IEI) who met the criteria to receive Evusheld. The researchers included patients on B-cell-depleting therapies or with humoral IEI who had received at least one dose of Evusheld and were later diagnosed with COVID-19, and they excluded those treated with B-cell-depleting therapies for cancer.
 

EVUSHELD was well tolerated

After extracting data on COVID-19 infection, vaccination status, and outcomes, they found that, between Jan. 18 and May 28, 2022, 412 patients with IMIDs or humoral IEI received Evusheld. No deaths occurred among these patients and, overall, they tolerated the medication well.

All 12 patients who experienced breakthrough COVID-19 infection were treated with B-cell-depleting therapies. Among the 12 patients:

• Six patients developed infection 13-84 (median 19) days after receiving 150 mg/150 mg tixagevimab/cilgavimab.
• Six patients developed infection 19-72 (median of 38.5) days after either a single dose of 300 mg/300 mg or a second dose of 150 mg/150 mg.
• Eleven patients had mild illness and recovered at home; one patient was hospitalized and treated with high-flow oxygen. All cases had been vaccinated against COVID-19 (five received two vaccinations, six received three, and one received four).
• One possible serious adverse event involved a patient with COVID-19 and immune-mediated thrombocytopenia (ITP) who was hospitalized soon after receiving Evusheld with ITP flare that resolved with intravenous immunoglobulin.

Dr. Calabrese acknowledged limitations to the study, including few patients, lack of a comparator group, and the study period falling during the Omicron wave.

“Also, nine of the breakthrough cases received additional COVID-19 therapy (oral antiviral or monoclonal antibody), which falls within standard of care for this high-risk group but prevents ascribing effectiveness to individual components of the regimen,” she added.

“Evusheld is authorized for PrEP against COVID-19 in patients at high risk for severe COVID due to suboptimal vaccine responses. This includes patients receiving B-cell-depleting drugs like rituximab, and patients with inborn errors of humoral immunity,” Dr. Calabrese explained.

“It is well known that this group of patients is at very high risk for severe COVID and death, even when fully vaccinated, and it has become clear that more strategies are needed to protect this vulnerable group, including use of Evusheld as well as aggressive treatment if infected,” she added.  
 

Evusheld not always easy to obtain

Although the medication has been available in the United States since January 2022, Dr. Calabrese said, patients may not receive it because of barriers including lack of both awareness and access.

Davey Smith, MD, professor of medicine and head of infectious diseases and global public health at the University of California San Diego, in La Jolla, said in an interview that he was not surprised by the results, but added that the study was conducted in too few patients to draw any strong conclusions or affect patient care.

“This small study that showed that breakthrough infections occurred but were generally mild, provides a small glimpse of real-world use of tixagevimab/cilgavimab as PrEP for immunocompromised persons,” said Dr. Smith, who was not involved in the study.

“In the setting of Omicron and vaccination, I would expect the same outcomes reported even without the treatment,” he added.

Dr. Smith recommends larger related randomized, controlled trials to provide clinicians with sufficient data to guide them in their patient care.

Graham Snyder, MD, associate professor in the division of infectious diseases at the University of Pittsburgh and medical director of infection prevention and hospital epidemiology at the University of Pittsburgh Medical Center, noted that the study “adds to a quickly growing literature on the real-world benefits of tixagevimab/cilgavimab to protect vulnerable individuals with weakened immune systems from the complications of COVID-19.

“This study provides a modest addition to our understanding of the role and benefit of Evusheld,” Dr. Snyder said in an interview. “By characterizing only patients who have received Evusheld without an untreated comparison group, we can’t draw any inference about the extent of benefit the agent provided to these patients.

“Substantial data already show that this agent is effective in preventing complications of COVID-19 infection in immunocompromised individuals,” added Dr. Snyder, who was not involved in the study.

“ ‘Immunocompromised’ represents a very diverse set of clinical conditions,” he said. “The research agenda should therefore focus on a more refined description of the effect in specific populations and a continued understanding of the effect of Evusheld in the context of updated vaccination strategies and changing virus ecology.”

Dr. Calabrese and her colleagues wrote that larger, controlled trials are underway.

 

FDA: Evusheld may not neutralize certain SARS-CoV-2 variants

“The biggest unanswered question is how Evusheld will hold up against new variants,” Dr. Calabrese said.

In an Oct. 3, 2022, update, the Food and Drug Administration released a statement about the risk of developing COVID-19 from SARS-CoV-2 variants that are not neutralized by Evusheld. The statement mentions an updated fact sheet that describes reduced protection from Evusheld against the Omicron subvariant BA.4.6, which accounted for nearly 13% of all new COVID-19 cases in the United States in the week ending Oct. 1.

There was no outside funding for the study. Dr. Smith reported no relevant financial conflicts of interest. Dr. Snyder said he is an unpaid adviser to an AstraZeneca observational study that’s assessing the real-world effectiveness of Evusheld.