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Lupus patients in remission see more flares with HCQ reduction, discontinuation
Continuation of hydroxychloroquine (HCQ) when a patient’s systemic lupus erythematosus (SLE) is in remission or has very low disease activity is linked to a lower risk of flares than is reducing or stopping the antimalarial drug, according to new research presented at the virtual annual meeting of the American College of Rheumatology.
“Though HCQ is a cornerstone SLE drug, physicians and patients often consider lowering or stopping the drug during remission or low disease activity in order to limit long-term toxicity,” Sasha Bernatsky, MD, PhD, a professor of rheumatology at McGill University in Montreal, told attendees. Her group’s findings revealed a 20% increased risk of flares in those who reduced their HCQ dose and a 56% greater risk of flares in those who discontinued HCQ, compared with those who continued on a maintenance dose.
“I’m going to be using these results in discussions with my patients regarding what the potential implications are of lowering or stopping hydroxychloroquine,” Dr. Bernatsky told attendees. “I think, in the end, this information should be in their hands so that they can be the ones to make these decisions with us, and, of course, given the significant flare rates even in remission, we need to keep on working on optimizing lupus treatments.”
Study details
The researchers analyzed prospective data from 1,460 patients enrolled in the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) cohort, which includes 33 sites across Europe, Asia, and North America. Patients in this cohort undergo annual follow-ups after enrollment within 15 months of their diagnosis. The study population was 89% female and 52% white. All participants either had low disease activity, defined as a score of 4 or lower on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and/or as a prednisone dose no greater than 7.5 mg/day, or were in complete remission, defined as a 0 on SLEDAI-2K while receiving no therapy, including no prednisone or immunosuppressives in the past year.
In addition to adjusting for sex, race/ethnicity, age, education, and geographic residence, the researchers took into account baseline SLE duration, renal damage, body mass index, smoking status, and use of prednisone, immunosuppressives, and biologics. For the outcome of time to first flare, the researchers analyzed those who discontinued HCQ separately from those who reduced the dose, comparing each to those who continued HCQ maintenance therapy. The researchers defined first flare as either hospitalization because of SLE, increased disease activity (at least 4 points on the SLEDAI-2K), or therapy augmentation with steroids, immunosuppressives, antimalarials, or biologics.
Within each cohort, patients who reduced or stopped HCQ therapy were matched to patients who continued HCQ maintenance therapy based on duration of HCQ since time zero, the point at which participants were considered at risk for SLE flares. In the reduction cohort, time zero was the date of a participant’s first HCQ reduction; in the discontinuation cohort, time zero was the date a participant stopped the therapy. Because of the study’s design and reliance on person-years of exposure, it was possible for a single participant to contribute data to more than one cohort.
Results
The overall cohort examining reduction of HCQ dose included 564 patients who reduced their dose, contributing 1,063 person-years of data, and 778 matched patients who started HCQ at the same time but continued HCQ maintenance therapy without a dose reduction, contributing 1,242 person-years. The average duration of HCQ use since time zero in this cohort was 3.4 years.
Before stratifying for disease activity, the group who reduced their therapy experienced 40 first flares per 100 person-years, compared with 31.9 first flares per 100 person-years on maintenance therapy. Those who reduced HCQ had a 20% greater risk of flares than did those who continued it (adjusted hazard ratio, 1.2). However, when those in remission were compared with those not in remission – independent of disease activity level – patients in remission were twice as likely to experience a flare if they reduced their HCQ dose (aHR, 2.14).
In the discontinuation cohort, 389 patients who stopped HCQ therapy contributed 657 person-years, and 577 matched patients who continued HCQ maintenance therapy contributed 924 person-years. The average duration of HCQ use since time zero in this cohort was 4.2 years. Before stratifying for disease activity, the average number of first flares per 100 person-years was 41.3 in the HCQ discontinuation group and 30 in the HCQ maintenance group, resulting in a 56% higher risk of flares for those who stopped HCQ, compared with patients who continued HCQ (aHR, 1.56). Looking only at those in remission, patients were nearly three times more likely to experience a flare if they stopped HCQ than were patients not in remission who continued a maintenance dose (aHR, 2.77).
Patient age is an important consideration
Overall, these findings are not surprising, said Jill P. Buyon, MD, director of the division of rheumatology and of the Lupus Center at NYU-Langone Health in New York. Dr. Buyon is not involved in the current study but is studying discontinuation of HCQ in older adults with lupus.
“It has been already shown that when lupus patients discontinue HCQ, flares are more likely, but does this apply to all age groups?” Dr. Buyon asked in an interview. “Data are essential to more accurately weigh the balance between accumulating ocular exposure, the explosion of new tools to assess retinal injury, and the risk of disease flare in a population that may have more stable/quiescent disease than younger patients.”
Although HCQ’s track record with infection risk is consistently better than that of more immunosuppressive drugs and is very safe during pregnancy, Dr. Buyon said her “ophthalmology colleagues persistently emphasize the risk of retinal accumulation of drug and ocular toxicity over time.” She referenced a recent case-control study in which overall prevalence of HCQ retinopathy was 7.5%, and greater for patients taking more than 5 mg/kg of HCQ or who used HCQ for more than 10 years.
”Risk escalates with continued use, and evaluation by sensitive approaches such as multifocal electroretinography suggests nearly a third of patients accrue retinal damage,” Dr. Buyon said. “As the longevity of patients improves and comorbidities such as renal insufficiency (which affects HCQ clearance) may increase, the ratio of efficacy to toxicity would be expected to decrease.” Further, the fact that disease activity may wane as people age means that rheumatologists treating older adults need to address a critical question, she said: “Can HCQ be safely withdrawn? This question is important in the context of an even broader concern regarding management of SLE in the elderly population, a topic which has received minimal attention.”
The study is limited by its observational design and the fact that the intervention was not randomly allocated, although the researchers attempted to adjust for confounders. Dr. Bernatsky also noted that mild flares might have been missed, and the researchers did not evaluate HCQ levels or adherence, nor did the data set include physicians’ or patients’ explicitly stated reasons for HCQ reduction or discontinuation.
”We estimated that 5% of patients may have reduced HCQ therapy as result of the AAO [American Academy of Ophthalmology] guidelines, 55% because of low disease activity state, and the remainder (40%) for other reasons, possibly intolerance or patient preference,” the researchers noted in their abstract. “Among those who discontinued HCQ, 4% had retinal changes of concern, 15% were in clinical remission, and the remainder stopped for unknown reasons, possibly intolerance or patient preference.”
Dr. Buyon also pointed out that the cohort was initially intended for studying cardiovascular risk and not designed to capture all visits during each year of follow-up.
“Thus, while hospitalizations would be well captured, not all flares, particularly those not severe, would be captured, and thus we may not have the complete picture,” she said, reiterating Dr. Bernatsky’s point that mild flares may have been missed.
”Clearly, this is a very important topic for the management of our patients, particularly those who are elderly and may have already reaped the benefits of hydroxychloroquine,” Dr. Buyon said. “Of course, we have to be mindful of the potential benefit with regard to blood clotting and lipid lowering. Nevertheless, accumulated ocular toxicity and cardiac issues such as cardiomyopathy may emerge to tip the balance after years of accumulated drug exposure.”
The research was funded by the Canadian Institute of Health Research, the Singer Family Fund for Lupus Research, and the SLICC Group. Dr. Bernatsky had no disclosures. Dr. Buyon noted that she has an R34 NIH planning grant to study the safety of withdrawal of hydroxychloroquine in elderly lupus patients that is relevant to this study.
Continuation of hydroxychloroquine (HCQ) when a patient’s systemic lupus erythematosus (SLE) is in remission or has very low disease activity is linked to a lower risk of flares than is reducing or stopping the antimalarial drug, according to new research presented at the virtual annual meeting of the American College of Rheumatology.
“Though HCQ is a cornerstone SLE drug, physicians and patients often consider lowering or stopping the drug during remission or low disease activity in order to limit long-term toxicity,” Sasha Bernatsky, MD, PhD, a professor of rheumatology at McGill University in Montreal, told attendees. Her group’s findings revealed a 20% increased risk of flares in those who reduced their HCQ dose and a 56% greater risk of flares in those who discontinued HCQ, compared with those who continued on a maintenance dose.
“I’m going to be using these results in discussions with my patients regarding what the potential implications are of lowering or stopping hydroxychloroquine,” Dr. Bernatsky told attendees. “I think, in the end, this information should be in their hands so that they can be the ones to make these decisions with us, and, of course, given the significant flare rates even in remission, we need to keep on working on optimizing lupus treatments.”
Study details
The researchers analyzed prospective data from 1,460 patients enrolled in the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) cohort, which includes 33 sites across Europe, Asia, and North America. Patients in this cohort undergo annual follow-ups after enrollment within 15 months of their diagnosis. The study population was 89% female and 52% white. All participants either had low disease activity, defined as a score of 4 or lower on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and/or as a prednisone dose no greater than 7.5 mg/day, or were in complete remission, defined as a 0 on SLEDAI-2K while receiving no therapy, including no prednisone or immunosuppressives in the past year.
In addition to adjusting for sex, race/ethnicity, age, education, and geographic residence, the researchers took into account baseline SLE duration, renal damage, body mass index, smoking status, and use of prednisone, immunosuppressives, and biologics. For the outcome of time to first flare, the researchers analyzed those who discontinued HCQ separately from those who reduced the dose, comparing each to those who continued HCQ maintenance therapy. The researchers defined first flare as either hospitalization because of SLE, increased disease activity (at least 4 points on the SLEDAI-2K), or therapy augmentation with steroids, immunosuppressives, antimalarials, or biologics.
Within each cohort, patients who reduced or stopped HCQ therapy were matched to patients who continued HCQ maintenance therapy based on duration of HCQ since time zero, the point at which participants were considered at risk for SLE flares. In the reduction cohort, time zero was the date of a participant’s first HCQ reduction; in the discontinuation cohort, time zero was the date a participant stopped the therapy. Because of the study’s design and reliance on person-years of exposure, it was possible for a single participant to contribute data to more than one cohort.
Results
The overall cohort examining reduction of HCQ dose included 564 patients who reduced their dose, contributing 1,063 person-years of data, and 778 matched patients who started HCQ at the same time but continued HCQ maintenance therapy without a dose reduction, contributing 1,242 person-years. The average duration of HCQ use since time zero in this cohort was 3.4 years.
Before stratifying for disease activity, the group who reduced their therapy experienced 40 first flares per 100 person-years, compared with 31.9 first flares per 100 person-years on maintenance therapy. Those who reduced HCQ had a 20% greater risk of flares than did those who continued it (adjusted hazard ratio, 1.2). However, when those in remission were compared with those not in remission – independent of disease activity level – patients in remission were twice as likely to experience a flare if they reduced their HCQ dose (aHR, 2.14).
In the discontinuation cohort, 389 patients who stopped HCQ therapy contributed 657 person-years, and 577 matched patients who continued HCQ maintenance therapy contributed 924 person-years. The average duration of HCQ use since time zero in this cohort was 4.2 years. Before stratifying for disease activity, the average number of first flares per 100 person-years was 41.3 in the HCQ discontinuation group and 30 in the HCQ maintenance group, resulting in a 56% higher risk of flares for those who stopped HCQ, compared with patients who continued HCQ (aHR, 1.56). Looking only at those in remission, patients were nearly three times more likely to experience a flare if they stopped HCQ than were patients not in remission who continued a maintenance dose (aHR, 2.77).
Patient age is an important consideration
Overall, these findings are not surprising, said Jill P. Buyon, MD, director of the division of rheumatology and of the Lupus Center at NYU-Langone Health in New York. Dr. Buyon is not involved in the current study but is studying discontinuation of HCQ in older adults with lupus.
“It has been already shown that when lupus patients discontinue HCQ, flares are more likely, but does this apply to all age groups?” Dr. Buyon asked in an interview. “Data are essential to more accurately weigh the balance between accumulating ocular exposure, the explosion of new tools to assess retinal injury, and the risk of disease flare in a population that may have more stable/quiescent disease than younger patients.”
Although HCQ’s track record with infection risk is consistently better than that of more immunosuppressive drugs and is very safe during pregnancy, Dr. Buyon said her “ophthalmology colleagues persistently emphasize the risk of retinal accumulation of drug and ocular toxicity over time.” She referenced a recent case-control study in which overall prevalence of HCQ retinopathy was 7.5%, and greater for patients taking more than 5 mg/kg of HCQ or who used HCQ for more than 10 years.
”Risk escalates with continued use, and evaluation by sensitive approaches such as multifocal electroretinography suggests nearly a third of patients accrue retinal damage,” Dr. Buyon said. “As the longevity of patients improves and comorbidities such as renal insufficiency (which affects HCQ clearance) may increase, the ratio of efficacy to toxicity would be expected to decrease.” Further, the fact that disease activity may wane as people age means that rheumatologists treating older adults need to address a critical question, she said: “Can HCQ be safely withdrawn? This question is important in the context of an even broader concern regarding management of SLE in the elderly population, a topic which has received minimal attention.”
The study is limited by its observational design and the fact that the intervention was not randomly allocated, although the researchers attempted to adjust for confounders. Dr. Bernatsky also noted that mild flares might have been missed, and the researchers did not evaluate HCQ levels or adherence, nor did the data set include physicians’ or patients’ explicitly stated reasons for HCQ reduction or discontinuation.
”We estimated that 5% of patients may have reduced HCQ therapy as result of the AAO [American Academy of Ophthalmology] guidelines, 55% because of low disease activity state, and the remainder (40%) for other reasons, possibly intolerance or patient preference,” the researchers noted in their abstract. “Among those who discontinued HCQ, 4% had retinal changes of concern, 15% were in clinical remission, and the remainder stopped for unknown reasons, possibly intolerance or patient preference.”
Dr. Buyon also pointed out that the cohort was initially intended for studying cardiovascular risk and not designed to capture all visits during each year of follow-up.
“Thus, while hospitalizations would be well captured, not all flares, particularly those not severe, would be captured, and thus we may not have the complete picture,” she said, reiterating Dr. Bernatsky’s point that mild flares may have been missed.
”Clearly, this is a very important topic for the management of our patients, particularly those who are elderly and may have already reaped the benefits of hydroxychloroquine,” Dr. Buyon said. “Of course, we have to be mindful of the potential benefit with regard to blood clotting and lipid lowering. Nevertheless, accumulated ocular toxicity and cardiac issues such as cardiomyopathy may emerge to tip the balance after years of accumulated drug exposure.”
The research was funded by the Canadian Institute of Health Research, the Singer Family Fund for Lupus Research, and the SLICC Group. Dr. Bernatsky had no disclosures. Dr. Buyon noted that she has an R34 NIH planning grant to study the safety of withdrawal of hydroxychloroquine in elderly lupus patients that is relevant to this study.
Continuation of hydroxychloroquine (HCQ) when a patient’s systemic lupus erythematosus (SLE) is in remission or has very low disease activity is linked to a lower risk of flares than is reducing or stopping the antimalarial drug, according to new research presented at the virtual annual meeting of the American College of Rheumatology.
“Though HCQ is a cornerstone SLE drug, physicians and patients often consider lowering or stopping the drug during remission or low disease activity in order to limit long-term toxicity,” Sasha Bernatsky, MD, PhD, a professor of rheumatology at McGill University in Montreal, told attendees. Her group’s findings revealed a 20% increased risk of flares in those who reduced their HCQ dose and a 56% greater risk of flares in those who discontinued HCQ, compared with those who continued on a maintenance dose.
“I’m going to be using these results in discussions with my patients regarding what the potential implications are of lowering or stopping hydroxychloroquine,” Dr. Bernatsky told attendees. “I think, in the end, this information should be in their hands so that they can be the ones to make these decisions with us, and, of course, given the significant flare rates even in remission, we need to keep on working on optimizing lupus treatments.”
Study details
The researchers analyzed prospective data from 1,460 patients enrolled in the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) cohort, which includes 33 sites across Europe, Asia, and North America. Patients in this cohort undergo annual follow-ups after enrollment within 15 months of their diagnosis. The study population was 89% female and 52% white. All participants either had low disease activity, defined as a score of 4 or lower on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and/or as a prednisone dose no greater than 7.5 mg/day, or were in complete remission, defined as a 0 on SLEDAI-2K while receiving no therapy, including no prednisone or immunosuppressives in the past year.
In addition to adjusting for sex, race/ethnicity, age, education, and geographic residence, the researchers took into account baseline SLE duration, renal damage, body mass index, smoking status, and use of prednisone, immunosuppressives, and biologics. For the outcome of time to first flare, the researchers analyzed those who discontinued HCQ separately from those who reduced the dose, comparing each to those who continued HCQ maintenance therapy. The researchers defined first flare as either hospitalization because of SLE, increased disease activity (at least 4 points on the SLEDAI-2K), or therapy augmentation with steroids, immunosuppressives, antimalarials, or biologics.
Within each cohort, patients who reduced or stopped HCQ therapy were matched to patients who continued HCQ maintenance therapy based on duration of HCQ since time zero, the point at which participants were considered at risk for SLE flares. In the reduction cohort, time zero was the date of a participant’s first HCQ reduction; in the discontinuation cohort, time zero was the date a participant stopped the therapy. Because of the study’s design and reliance on person-years of exposure, it was possible for a single participant to contribute data to more than one cohort.
Results
The overall cohort examining reduction of HCQ dose included 564 patients who reduced their dose, contributing 1,063 person-years of data, and 778 matched patients who started HCQ at the same time but continued HCQ maintenance therapy without a dose reduction, contributing 1,242 person-years. The average duration of HCQ use since time zero in this cohort was 3.4 years.
Before stratifying for disease activity, the group who reduced their therapy experienced 40 first flares per 100 person-years, compared with 31.9 first flares per 100 person-years on maintenance therapy. Those who reduced HCQ had a 20% greater risk of flares than did those who continued it (adjusted hazard ratio, 1.2). However, when those in remission were compared with those not in remission – independent of disease activity level – patients in remission were twice as likely to experience a flare if they reduced their HCQ dose (aHR, 2.14).
In the discontinuation cohort, 389 patients who stopped HCQ therapy contributed 657 person-years, and 577 matched patients who continued HCQ maintenance therapy contributed 924 person-years. The average duration of HCQ use since time zero in this cohort was 4.2 years. Before stratifying for disease activity, the average number of first flares per 100 person-years was 41.3 in the HCQ discontinuation group and 30 in the HCQ maintenance group, resulting in a 56% higher risk of flares for those who stopped HCQ, compared with patients who continued HCQ (aHR, 1.56). Looking only at those in remission, patients were nearly three times more likely to experience a flare if they stopped HCQ than were patients not in remission who continued a maintenance dose (aHR, 2.77).
Patient age is an important consideration
Overall, these findings are not surprising, said Jill P. Buyon, MD, director of the division of rheumatology and of the Lupus Center at NYU-Langone Health in New York. Dr. Buyon is not involved in the current study but is studying discontinuation of HCQ in older adults with lupus.
“It has been already shown that when lupus patients discontinue HCQ, flares are more likely, but does this apply to all age groups?” Dr. Buyon asked in an interview. “Data are essential to more accurately weigh the balance between accumulating ocular exposure, the explosion of new tools to assess retinal injury, and the risk of disease flare in a population that may have more stable/quiescent disease than younger patients.”
Although HCQ’s track record with infection risk is consistently better than that of more immunosuppressive drugs and is very safe during pregnancy, Dr. Buyon said her “ophthalmology colleagues persistently emphasize the risk of retinal accumulation of drug and ocular toxicity over time.” She referenced a recent case-control study in which overall prevalence of HCQ retinopathy was 7.5%, and greater for patients taking more than 5 mg/kg of HCQ or who used HCQ for more than 10 years.
”Risk escalates with continued use, and evaluation by sensitive approaches such as multifocal electroretinography suggests nearly a third of patients accrue retinal damage,” Dr. Buyon said. “As the longevity of patients improves and comorbidities such as renal insufficiency (which affects HCQ clearance) may increase, the ratio of efficacy to toxicity would be expected to decrease.” Further, the fact that disease activity may wane as people age means that rheumatologists treating older adults need to address a critical question, she said: “Can HCQ be safely withdrawn? This question is important in the context of an even broader concern regarding management of SLE in the elderly population, a topic which has received minimal attention.”
The study is limited by its observational design and the fact that the intervention was not randomly allocated, although the researchers attempted to adjust for confounders. Dr. Bernatsky also noted that mild flares might have been missed, and the researchers did not evaluate HCQ levels or adherence, nor did the data set include physicians’ or patients’ explicitly stated reasons for HCQ reduction or discontinuation.
”We estimated that 5% of patients may have reduced HCQ therapy as result of the AAO [American Academy of Ophthalmology] guidelines, 55% because of low disease activity state, and the remainder (40%) for other reasons, possibly intolerance or patient preference,” the researchers noted in their abstract. “Among those who discontinued HCQ, 4% had retinal changes of concern, 15% were in clinical remission, and the remainder stopped for unknown reasons, possibly intolerance or patient preference.”
Dr. Buyon also pointed out that the cohort was initially intended for studying cardiovascular risk and not designed to capture all visits during each year of follow-up.
“Thus, while hospitalizations would be well captured, not all flares, particularly those not severe, would be captured, and thus we may not have the complete picture,” she said, reiterating Dr. Bernatsky’s point that mild flares may have been missed.
”Clearly, this is a very important topic for the management of our patients, particularly those who are elderly and may have already reaped the benefits of hydroxychloroquine,” Dr. Buyon said. “Of course, we have to be mindful of the potential benefit with regard to blood clotting and lipid lowering. Nevertheless, accumulated ocular toxicity and cardiac issues such as cardiomyopathy may emerge to tip the balance after years of accumulated drug exposure.”
The research was funded by the Canadian Institute of Health Research, the Singer Family Fund for Lupus Research, and the SLICC Group. Dr. Bernatsky had no disclosures. Dr. Buyon noted that she has an R34 NIH planning grant to study the safety of withdrawal of hydroxychloroquine in elderly lupus patients that is relevant to this study.
FROM ACR 2021
Rituximab improves systemic sclerosis skin, lung symptoms
Rituximab effectively reduced skin sclerosis and appeared to have a beneficial effect on interstitial lung disease (ILD) for patients with systemic sclerosis (SSc) in a randomized, clinical trial.
At 24 weeks’ follow-up, there was significant improvement in total skin thickness scores among patients who received four once-weekly rituximab infusions, compared with patients who received placebo infusions. Among patients who received rituximab, there were also small but significant improvements in percentage of forced vital capacity (FVC). Among patients who received placebo, FVC worsened, reported Ayumi Yoshizaki, MD, of the University of Tokyo and colleagues.
“Systemic sclerosis is considered to have high unmet medical needs because of its poor prognosis and the lack of satisfactory and effective treatments,” he said at the virtual annual meeting of the American College of Rheumatology.
“Several clinical studies have suggested that B-cell depletion therapy with rituximab anti-CD20 antibody is effective in treating skin and lung fibrosis of SSc. However, no randomized, placebo-controlled trial has been able to confirm the efficacy of rituximab in SSc,” Dr. Yoshizaki said.
A rheumatologist who is currently conducting an investigator-initiated trial in which patients with SSC are undergoing treatment with rituximab followed by belimumab (Benlysta) said in an interview that he found the data to be “super interesting.”
“There are a lot of reasons to think that B cells might be important in systemic sclerosis, and actually that’s why our group had previously done an investigator-initiated trial with belimumab years ago,” said Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery in New York.
Randomized trial
Dr. Yoshizaki and colleagues conducted the randomized, placebo-controlled DESIRES trial in four hospitals in Japan to evaluate the safety and efficacy of rituximab for the treatment of SSc.
In the investigator-initiated trial, patients aged 20-79 years who fulfilled ACR and European Alliance of Associations for Rheumatology classification criteria for systemic sclerosis and who had a modified Rodnan Skin Score (mRSS) of 10 or more and a life expectancy of at least 6 months were randomly assigned to receive infusions with either rituximab 375 mg/m2 or placebo once weekly for 4 weeks. Patients and clinicians were masked to treatment allocation.
The trial included 56 patients (51 women, 5 men). Of all patients enrolled, 27 of 28 who were allocated to receive rituximab and 22 of 28 who were allocated to receive placebo underwent at least one infusion and completed 24 weeks of follow-up.
The absolute change in mRSS at 24 weeks after the start of therapy, the primary endpoint, was –6.30 in the rituximab group, compared with +2.14 in the placebo group, a difference of –8.44 (P < .0001).
In a subgroup analysis, rituximab was superior to placebo regardless of disease duration, disease type (diffuse cutaneous or limited cutaneous SSc), prior receipt of systemic corticosteroids or immunosuppressants, or having C-reactive protein levels less than 0.3 mg/dL or at least 0.3 mg/dL.
However, there was no significant benefit with rituximab for patients with baseline mRSS of at least 20 or for those without ILD at baseline.
There was also evidence that rituximab reduced lung fibrosis. For patients assigned to the active drug, the absolute change in FVC at 24 weeks was +0.09% of the predicted value, compared with –3.56% for patients who received placebo (P = .044).
The researchers also observed radiographic evidence of lung improvement. The absolute change in the percentage of lung field occupied with interstitial shadows was –0.32% in the rituximab arm versus +2.39% in the placebo arm (P = .034). There was no significant between-group difference in the absolute change in diffusing capacity of lung for carbon monoxide, however.
Adverse events that occurred more frequently with rituximab included oral mucositis, diarrhea, and decreased neutrophil and white blood cell counts.
Convincing results
“What I thought the Japanese study did was to give a much more convincing proof of concept than has been out there,” Dr. Spiera said in an interview.
“There have been some preliminary experiences that have been encouraging with rituximab in scleroderma, most of which has been open label,” he said.
He also referred to a retrospective study by EUSTAR, the European Scleroderma Trials and Research group, which indicated that patients who had previously received rituximab seemed to have had better outcomes than patients who had been treated with other therapies.
Dr. Spiera added that, although he was glad to see the data from a randomized, placebo-controlled trial in this population, he was uncomfortable with the idea of leaving patients untreated for 6 months.
“From the standpoint of somebody wanting to know what strategies might be promising, this is great for us, but I would not have designed the trial that way,” he said.
The study results were previously published in the Lancet Rheumatology.
The study was supported by grants from the Japan Agency for Medical Research and Development and Zenyaku Kogyo. Dr. Yoshizaki disclosed no relevant financial relationships. Dr. Spiera has received grant/research support from and has consulted for Roche/Genentech, maker of rituximab, and has received compensation from other companies.
A version of this article first appeared on Medscape.com.
Rituximab effectively reduced skin sclerosis and appeared to have a beneficial effect on interstitial lung disease (ILD) for patients with systemic sclerosis (SSc) in a randomized, clinical trial.
At 24 weeks’ follow-up, there was significant improvement in total skin thickness scores among patients who received four once-weekly rituximab infusions, compared with patients who received placebo infusions. Among patients who received rituximab, there were also small but significant improvements in percentage of forced vital capacity (FVC). Among patients who received placebo, FVC worsened, reported Ayumi Yoshizaki, MD, of the University of Tokyo and colleagues.
“Systemic sclerosis is considered to have high unmet medical needs because of its poor prognosis and the lack of satisfactory and effective treatments,” he said at the virtual annual meeting of the American College of Rheumatology.
“Several clinical studies have suggested that B-cell depletion therapy with rituximab anti-CD20 antibody is effective in treating skin and lung fibrosis of SSc. However, no randomized, placebo-controlled trial has been able to confirm the efficacy of rituximab in SSc,” Dr. Yoshizaki said.
A rheumatologist who is currently conducting an investigator-initiated trial in which patients with SSC are undergoing treatment with rituximab followed by belimumab (Benlysta) said in an interview that he found the data to be “super interesting.”
“There are a lot of reasons to think that B cells might be important in systemic sclerosis, and actually that’s why our group had previously done an investigator-initiated trial with belimumab years ago,” said Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery in New York.
Randomized trial
Dr. Yoshizaki and colleagues conducted the randomized, placebo-controlled DESIRES trial in four hospitals in Japan to evaluate the safety and efficacy of rituximab for the treatment of SSc.
In the investigator-initiated trial, patients aged 20-79 years who fulfilled ACR and European Alliance of Associations for Rheumatology classification criteria for systemic sclerosis and who had a modified Rodnan Skin Score (mRSS) of 10 or more and a life expectancy of at least 6 months were randomly assigned to receive infusions with either rituximab 375 mg/m2 or placebo once weekly for 4 weeks. Patients and clinicians were masked to treatment allocation.
The trial included 56 patients (51 women, 5 men). Of all patients enrolled, 27 of 28 who were allocated to receive rituximab and 22 of 28 who were allocated to receive placebo underwent at least one infusion and completed 24 weeks of follow-up.
The absolute change in mRSS at 24 weeks after the start of therapy, the primary endpoint, was –6.30 in the rituximab group, compared with +2.14 in the placebo group, a difference of –8.44 (P < .0001).
In a subgroup analysis, rituximab was superior to placebo regardless of disease duration, disease type (diffuse cutaneous or limited cutaneous SSc), prior receipt of systemic corticosteroids or immunosuppressants, or having C-reactive protein levels less than 0.3 mg/dL or at least 0.3 mg/dL.
However, there was no significant benefit with rituximab for patients with baseline mRSS of at least 20 or for those without ILD at baseline.
There was also evidence that rituximab reduced lung fibrosis. For patients assigned to the active drug, the absolute change in FVC at 24 weeks was +0.09% of the predicted value, compared with –3.56% for patients who received placebo (P = .044).
The researchers also observed radiographic evidence of lung improvement. The absolute change in the percentage of lung field occupied with interstitial shadows was –0.32% in the rituximab arm versus +2.39% in the placebo arm (P = .034). There was no significant between-group difference in the absolute change in diffusing capacity of lung for carbon monoxide, however.
Adverse events that occurred more frequently with rituximab included oral mucositis, diarrhea, and decreased neutrophil and white blood cell counts.
Convincing results
“What I thought the Japanese study did was to give a much more convincing proof of concept than has been out there,” Dr. Spiera said in an interview.
“There have been some preliminary experiences that have been encouraging with rituximab in scleroderma, most of which has been open label,” he said.
He also referred to a retrospective study by EUSTAR, the European Scleroderma Trials and Research group, which indicated that patients who had previously received rituximab seemed to have had better outcomes than patients who had been treated with other therapies.
Dr. Spiera added that, although he was glad to see the data from a randomized, placebo-controlled trial in this population, he was uncomfortable with the idea of leaving patients untreated for 6 months.
“From the standpoint of somebody wanting to know what strategies might be promising, this is great for us, but I would not have designed the trial that way,” he said.
The study results were previously published in the Lancet Rheumatology.
The study was supported by grants from the Japan Agency for Medical Research and Development and Zenyaku Kogyo. Dr. Yoshizaki disclosed no relevant financial relationships. Dr. Spiera has received grant/research support from and has consulted for Roche/Genentech, maker of rituximab, and has received compensation from other companies.
A version of this article first appeared on Medscape.com.
Rituximab effectively reduced skin sclerosis and appeared to have a beneficial effect on interstitial lung disease (ILD) for patients with systemic sclerosis (SSc) in a randomized, clinical trial.
At 24 weeks’ follow-up, there was significant improvement in total skin thickness scores among patients who received four once-weekly rituximab infusions, compared with patients who received placebo infusions. Among patients who received rituximab, there were also small but significant improvements in percentage of forced vital capacity (FVC). Among patients who received placebo, FVC worsened, reported Ayumi Yoshizaki, MD, of the University of Tokyo and colleagues.
“Systemic sclerosis is considered to have high unmet medical needs because of its poor prognosis and the lack of satisfactory and effective treatments,” he said at the virtual annual meeting of the American College of Rheumatology.
“Several clinical studies have suggested that B-cell depletion therapy with rituximab anti-CD20 antibody is effective in treating skin and lung fibrosis of SSc. However, no randomized, placebo-controlled trial has been able to confirm the efficacy of rituximab in SSc,” Dr. Yoshizaki said.
A rheumatologist who is currently conducting an investigator-initiated trial in which patients with SSC are undergoing treatment with rituximab followed by belimumab (Benlysta) said in an interview that he found the data to be “super interesting.”
“There are a lot of reasons to think that B cells might be important in systemic sclerosis, and actually that’s why our group had previously done an investigator-initiated trial with belimumab years ago,” said Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at the Hospital for Special Surgery in New York.
Randomized trial
Dr. Yoshizaki and colleagues conducted the randomized, placebo-controlled DESIRES trial in four hospitals in Japan to evaluate the safety and efficacy of rituximab for the treatment of SSc.
In the investigator-initiated trial, patients aged 20-79 years who fulfilled ACR and European Alliance of Associations for Rheumatology classification criteria for systemic sclerosis and who had a modified Rodnan Skin Score (mRSS) of 10 or more and a life expectancy of at least 6 months were randomly assigned to receive infusions with either rituximab 375 mg/m2 or placebo once weekly for 4 weeks. Patients and clinicians were masked to treatment allocation.
The trial included 56 patients (51 women, 5 men). Of all patients enrolled, 27 of 28 who were allocated to receive rituximab and 22 of 28 who were allocated to receive placebo underwent at least one infusion and completed 24 weeks of follow-up.
The absolute change in mRSS at 24 weeks after the start of therapy, the primary endpoint, was –6.30 in the rituximab group, compared with +2.14 in the placebo group, a difference of –8.44 (P < .0001).
In a subgroup analysis, rituximab was superior to placebo regardless of disease duration, disease type (diffuse cutaneous or limited cutaneous SSc), prior receipt of systemic corticosteroids or immunosuppressants, or having C-reactive protein levels less than 0.3 mg/dL or at least 0.3 mg/dL.
However, there was no significant benefit with rituximab for patients with baseline mRSS of at least 20 or for those without ILD at baseline.
There was also evidence that rituximab reduced lung fibrosis. For patients assigned to the active drug, the absolute change in FVC at 24 weeks was +0.09% of the predicted value, compared with –3.56% for patients who received placebo (P = .044).
The researchers also observed radiographic evidence of lung improvement. The absolute change in the percentage of lung field occupied with interstitial shadows was –0.32% in the rituximab arm versus +2.39% in the placebo arm (P = .034). There was no significant between-group difference in the absolute change in diffusing capacity of lung for carbon monoxide, however.
Adverse events that occurred more frequently with rituximab included oral mucositis, diarrhea, and decreased neutrophil and white blood cell counts.
Convincing results
“What I thought the Japanese study did was to give a much more convincing proof of concept than has been out there,” Dr. Spiera said in an interview.
“There have been some preliminary experiences that have been encouraging with rituximab in scleroderma, most of which has been open label,” he said.
He also referred to a retrospective study by EUSTAR, the European Scleroderma Trials and Research group, which indicated that patients who had previously received rituximab seemed to have had better outcomes than patients who had been treated with other therapies.
Dr. Spiera added that, although he was glad to see the data from a randomized, placebo-controlled trial in this population, he was uncomfortable with the idea of leaving patients untreated for 6 months.
“From the standpoint of somebody wanting to know what strategies might be promising, this is great for us, but I would not have designed the trial that way,” he said.
The study results were previously published in the Lancet Rheumatology.
The study was supported by grants from the Japan Agency for Medical Research and Development and Zenyaku Kogyo. Dr. Yoshizaki disclosed no relevant financial relationships. Dr. Spiera has received grant/research support from and has consulted for Roche/Genentech, maker of rituximab, and has received compensation from other companies.
A version of this article first appeared on Medscape.com.
FROM ACR 2021
Vitamin D and omega-3 supplements reduce autoimmune disease risk
For those of us who cannot sit in the sun and fish all day, the next best thing for preventing autoimmune diseases may be supplementation with vitamin D and fish oil-derived omega-3 fatty acids, results of a large prospective randomized trial suggest.
Among nearly 26,000 adults enrolled in a randomized trial designed primarily to study the effects of vitamin D and omega-3 supplementation on incident cancer and cardiovascular disease, 5, and 5 years of omega-3 fatty acid supplementation was associated with an 18% reduction in confirmed and probable incident autoimmune diseases, reported Karen H. Costenbader, MD, MPH, of Brigham & Women’s Hospital in Boston.
“The clinical importance of these results is very high, given that these are nontoxic, well-tolerated supplements, and that there are no other known effective therapies to reduce the incidence of autoimmune diseases,” she said during the virtual annual meeting of the American College of Rheumatology.
“People do have to take the supplements a long time to start to see the reduction in risk, especially for vitamin D, but they make biological sense, and autoimmune diseases develop slowly over time, so taking it today isn’t going to reduce risk of developing something tomorrow,” Dr. Costenbader said in an interview.
“These supplements have other health benefits. Obviously, fish oil is anti-inflammatory, and vitamin D is good for osteoporosis prevention, especially in our patients who take glucocorticoids. People who are otherwise healthy and have a family history of autoimmune disease might also consider starting to take these supplements,” she said.
After watching her presentation, session co-moderator Gregg Silverman, MD, from the NYU Langone School of Medicine in New York, who was not involved in the study, commented “I’m going to [nutrition store] GNC to get some vitamins.”
When asked for comment, the other session moderator, Tracy Frech, MD, of Vanderbilt University, Nashville, said, “I think Dr. Costenbader’s work is very important and her presentation excellent. My current practice is replacement of vitamin D in all autoimmune disease patients with low levels and per bone health guidelines. Additionally, I discuss omega-3 supplementation with Sjögren’s [syndrome] patients as a consideration.”
Evidence base
Dr. Costenbader noted that in a 2013 observational study from France, vitamin D derived through ultraviolet (UV) light exposure was associated with a lower risk for incident Crohn’s disease but not ulcerative colitis, and in two analyses of data in 2014 from the Nurses’ Health Study, both high plasma levels of 25-OH vitamin D and geographic residence in areas of high UV exposure were associated with a decreased incidence of rheumatoid arthritis (RA).
Other observational studies have supported omega-3 fatty acids for their anti-inflammatory properties, including a 2005 Danish prospective cohort study showing a lower risk for RA in participants who reported higher levels of fatty fish intake. In a separate study conducted in 2017, healthy volunteers with higher omega-3 fatty acid/total lipid proportions in red blood cell membranes had a lower prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor and a lower incidence of progression to inflammatory arthritis, she said.
Ancillary study
Despite the evidence, however, there have been no prospective randomized trials to test the effects of either vitamin D or omega-3 fatty acid supplementation on the incidence of autoimmune disease over time.
To rectify this, Dr. Costenbader and colleagues piggybacked an ancillary study onto the Vitamin D and Omega-3 Trial (VITAL), which had primary outcomes of cancer and cardiovascular disease incidence.
A total of 25,871 participants were enrolled, including 12,786 men aged 50 and older, and 13,085 women aged 55 and older.
The study had a 2 x 2 factorial design, with patients randomly assigned to vitamin D 2,000 IU/day or placebo, and then further randomized to either 1 g/day omega-3 fatty acids or placebo in both the vitamin D and placebo primary randomization arms.
At baseline 16,956 participants were assayed for 25-OH vitamin D and plasma omega 3 index, the ratio of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to total fatty acids. Participants self-reported baseline and all incident autoimmune diseases annually, with the reports confirmed by medical record review and disease criteria whenever possible.
Results
At 5 years of follow-up, confirmed incident autoimmune diseases had occurred in 123 patients in the active vitamin D group, compared with 155 in the placebo vitamin D group, translating into a hazard ratio (HR) for vitamin D of 0.78 (P = .045).
In the active omega-3 arm, 130 participants developed an autoimmune disease, compared with 148 in the placebo omega-3 arm, which translated into a nonsignificant HR of 0.85.
There was no statistical interaction between the two supplements. The investigators did observe an interaction between vitamin D and body mass index, with the effect stronger among participants with low BMI (P = .02). There also was an interaction between omega-3 fatty acids with a family history of autoimmune disease (P = .03).
In multivariate analysis adjusted for age, sex, race, and other supplement arm, vitamin D alone was associated with an HR for incident autoimmune disease of 0.68 (P = .02), omega-3 alone was associated with a nonsignificant HR of 0.74, and the combination was associated with an HR of 0.69 (P = .03).
Dr. Costenbader and colleagues acknowledged that the study was limited by the lack of a high-risk or nutritionally-deficient population, where the effects of supplementation might be larger; the restriction of the sample to older adults; and to the difficulty of confirming incident autoimmune thyroid disease from patient reports.
Cheryl Koehn, an arthritis patient advocate from Vancouver, Canada, who was not involved in the study, commented in the “chat” section of the presentation that her rheumatologist “has recommended vitamin D for years now. Says basically everyone north of Boston is vitamin D deficient. I take 1,000 IU per day. Been taking it for years.” Ms. Koehn is the founder and president of Arthritis Consumer Experts, a website that provides education to those with arthritis.
“Agreed. I tell every patient to take vitamin D supplement,” commented Fatma Dedeoglu, MD, a rheumatologist at Boston Children’s Hospital.
A version of this article first appeared on Medscape.com.
For those of us who cannot sit in the sun and fish all day, the next best thing for preventing autoimmune diseases may be supplementation with vitamin D and fish oil-derived omega-3 fatty acids, results of a large prospective randomized trial suggest.
Among nearly 26,000 adults enrolled in a randomized trial designed primarily to study the effects of vitamin D and omega-3 supplementation on incident cancer and cardiovascular disease, 5, and 5 years of omega-3 fatty acid supplementation was associated with an 18% reduction in confirmed and probable incident autoimmune diseases, reported Karen H. Costenbader, MD, MPH, of Brigham & Women’s Hospital in Boston.
“The clinical importance of these results is very high, given that these are nontoxic, well-tolerated supplements, and that there are no other known effective therapies to reduce the incidence of autoimmune diseases,” she said during the virtual annual meeting of the American College of Rheumatology.
“People do have to take the supplements a long time to start to see the reduction in risk, especially for vitamin D, but they make biological sense, and autoimmune diseases develop slowly over time, so taking it today isn’t going to reduce risk of developing something tomorrow,” Dr. Costenbader said in an interview.
“These supplements have other health benefits. Obviously, fish oil is anti-inflammatory, and vitamin D is good for osteoporosis prevention, especially in our patients who take glucocorticoids. People who are otherwise healthy and have a family history of autoimmune disease might also consider starting to take these supplements,” she said.
After watching her presentation, session co-moderator Gregg Silverman, MD, from the NYU Langone School of Medicine in New York, who was not involved in the study, commented “I’m going to [nutrition store] GNC to get some vitamins.”
When asked for comment, the other session moderator, Tracy Frech, MD, of Vanderbilt University, Nashville, said, “I think Dr. Costenbader’s work is very important and her presentation excellent. My current practice is replacement of vitamin D in all autoimmune disease patients with low levels and per bone health guidelines. Additionally, I discuss omega-3 supplementation with Sjögren’s [syndrome] patients as a consideration.”
Evidence base
Dr. Costenbader noted that in a 2013 observational study from France, vitamin D derived through ultraviolet (UV) light exposure was associated with a lower risk for incident Crohn’s disease but not ulcerative colitis, and in two analyses of data in 2014 from the Nurses’ Health Study, both high plasma levels of 25-OH vitamin D and geographic residence in areas of high UV exposure were associated with a decreased incidence of rheumatoid arthritis (RA).
Other observational studies have supported omega-3 fatty acids for their anti-inflammatory properties, including a 2005 Danish prospective cohort study showing a lower risk for RA in participants who reported higher levels of fatty fish intake. In a separate study conducted in 2017, healthy volunteers with higher omega-3 fatty acid/total lipid proportions in red blood cell membranes had a lower prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor and a lower incidence of progression to inflammatory arthritis, she said.
Ancillary study
Despite the evidence, however, there have been no prospective randomized trials to test the effects of either vitamin D or omega-3 fatty acid supplementation on the incidence of autoimmune disease over time.
To rectify this, Dr. Costenbader and colleagues piggybacked an ancillary study onto the Vitamin D and Omega-3 Trial (VITAL), which had primary outcomes of cancer and cardiovascular disease incidence.
A total of 25,871 participants were enrolled, including 12,786 men aged 50 and older, and 13,085 women aged 55 and older.
The study had a 2 x 2 factorial design, with patients randomly assigned to vitamin D 2,000 IU/day or placebo, and then further randomized to either 1 g/day omega-3 fatty acids or placebo in both the vitamin D and placebo primary randomization arms.
At baseline 16,956 participants were assayed for 25-OH vitamin D and plasma omega 3 index, the ratio of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to total fatty acids. Participants self-reported baseline and all incident autoimmune diseases annually, with the reports confirmed by medical record review and disease criteria whenever possible.
Results
At 5 years of follow-up, confirmed incident autoimmune diseases had occurred in 123 patients in the active vitamin D group, compared with 155 in the placebo vitamin D group, translating into a hazard ratio (HR) for vitamin D of 0.78 (P = .045).
In the active omega-3 arm, 130 participants developed an autoimmune disease, compared with 148 in the placebo omega-3 arm, which translated into a nonsignificant HR of 0.85.
There was no statistical interaction between the two supplements. The investigators did observe an interaction between vitamin D and body mass index, with the effect stronger among participants with low BMI (P = .02). There also was an interaction between omega-3 fatty acids with a family history of autoimmune disease (P = .03).
In multivariate analysis adjusted for age, sex, race, and other supplement arm, vitamin D alone was associated with an HR for incident autoimmune disease of 0.68 (P = .02), omega-3 alone was associated with a nonsignificant HR of 0.74, and the combination was associated with an HR of 0.69 (P = .03).
Dr. Costenbader and colleagues acknowledged that the study was limited by the lack of a high-risk or nutritionally-deficient population, where the effects of supplementation might be larger; the restriction of the sample to older adults; and to the difficulty of confirming incident autoimmune thyroid disease from patient reports.
Cheryl Koehn, an arthritis patient advocate from Vancouver, Canada, who was not involved in the study, commented in the “chat” section of the presentation that her rheumatologist “has recommended vitamin D for years now. Says basically everyone north of Boston is vitamin D deficient. I take 1,000 IU per day. Been taking it for years.” Ms. Koehn is the founder and president of Arthritis Consumer Experts, a website that provides education to those with arthritis.
“Agreed. I tell every patient to take vitamin D supplement,” commented Fatma Dedeoglu, MD, a rheumatologist at Boston Children’s Hospital.
A version of this article first appeared on Medscape.com.
For those of us who cannot sit in the sun and fish all day, the next best thing for preventing autoimmune diseases may be supplementation with vitamin D and fish oil-derived omega-3 fatty acids, results of a large prospective randomized trial suggest.
Among nearly 26,000 adults enrolled in a randomized trial designed primarily to study the effects of vitamin D and omega-3 supplementation on incident cancer and cardiovascular disease, 5, and 5 years of omega-3 fatty acid supplementation was associated with an 18% reduction in confirmed and probable incident autoimmune diseases, reported Karen H. Costenbader, MD, MPH, of Brigham & Women’s Hospital in Boston.
“The clinical importance of these results is very high, given that these are nontoxic, well-tolerated supplements, and that there are no other known effective therapies to reduce the incidence of autoimmune diseases,” she said during the virtual annual meeting of the American College of Rheumatology.
“People do have to take the supplements a long time to start to see the reduction in risk, especially for vitamin D, but they make biological sense, and autoimmune diseases develop slowly over time, so taking it today isn’t going to reduce risk of developing something tomorrow,” Dr. Costenbader said in an interview.
“These supplements have other health benefits. Obviously, fish oil is anti-inflammatory, and vitamin D is good for osteoporosis prevention, especially in our patients who take glucocorticoids. People who are otherwise healthy and have a family history of autoimmune disease might also consider starting to take these supplements,” she said.
After watching her presentation, session co-moderator Gregg Silverman, MD, from the NYU Langone School of Medicine in New York, who was not involved in the study, commented “I’m going to [nutrition store] GNC to get some vitamins.”
When asked for comment, the other session moderator, Tracy Frech, MD, of Vanderbilt University, Nashville, said, “I think Dr. Costenbader’s work is very important and her presentation excellent. My current practice is replacement of vitamin D in all autoimmune disease patients with low levels and per bone health guidelines. Additionally, I discuss omega-3 supplementation with Sjögren’s [syndrome] patients as a consideration.”
Evidence base
Dr. Costenbader noted that in a 2013 observational study from France, vitamin D derived through ultraviolet (UV) light exposure was associated with a lower risk for incident Crohn’s disease but not ulcerative colitis, and in two analyses of data in 2014 from the Nurses’ Health Study, both high plasma levels of 25-OH vitamin D and geographic residence in areas of high UV exposure were associated with a decreased incidence of rheumatoid arthritis (RA).
Other observational studies have supported omega-3 fatty acids for their anti-inflammatory properties, including a 2005 Danish prospective cohort study showing a lower risk for RA in participants who reported higher levels of fatty fish intake. In a separate study conducted in 2017, healthy volunteers with higher omega-3 fatty acid/total lipid proportions in red blood cell membranes had a lower prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor and a lower incidence of progression to inflammatory arthritis, she said.
Ancillary study
Despite the evidence, however, there have been no prospective randomized trials to test the effects of either vitamin D or omega-3 fatty acid supplementation on the incidence of autoimmune disease over time.
To rectify this, Dr. Costenbader and colleagues piggybacked an ancillary study onto the Vitamin D and Omega-3 Trial (VITAL), which had primary outcomes of cancer and cardiovascular disease incidence.
A total of 25,871 participants were enrolled, including 12,786 men aged 50 and older, and 13,085 women aged 55 and older.
The study had a 2 x 2 factorial design, with patients randomly assigned to vitamin D 2,000 IU/day or placebo, and then further randomized to either 1 g/day omega-3 fatty acids or placebo in both the vitamin D and placebo primary randomization arms.
At baseline 16,956 participants were assayed for 25-OH vitamin D and plasma omega 3 index, the ratio of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to total fatty acids. Participants self-reported baseline and all incident autoimmune diseases annually, with the reports confirmed by medical record review and disease criteria whenever possible.
Results
At 5 years of follow-up, confirmed incident autoimmune diseases had occurred in 123 patients in the active vitamin D group, compared with 155 in the placebo vitamin D group, translating into a hazard ratio (HR) for vitamin D of 0.78 (P = .045).
In the active omega-3 arm, 130 participants developed an autoimmune disease, compared with 148 in the placebo omega-3 arm, which translated into a nonsignificant HR of 0.85.
There was no statistical interaction between the two supplements. The investigators did observe an interaction between vitamin D and body mass index, with the effect stronger among participants with low BMI (P = .02). There also was an interaction between omega-3 fatty acids with a family history of autoimmune disease (P = .03).
In multivariate analysis adjusted for age, sex, race, and other supplement arm, vitamin D alone was associated with an HR for incident autoimmune disease of 0.68 (P = .02), omega-3 alone was associated with a nonsignificant HR of 0.74, and the combination was associated with an HR of 0.69 (P = .03).
Dr. Costenbader and colleagues acknowledged that the study was limited by the lack of a high-risk or nutritionally-deficient population, where the effects of supplementation might be larger; the restriction of the sample to older adults; and to the difficulty of confirming incident autoimmune thyroid disease from patient reports.
Cheryl Koehn, an arthritis patient advocate from Vancouver, Canada, who was not involved in the study, commented in the “chat” section of the presentation that her rheumatologist “has recommended vitamin D for years now. Says basically everyone north of Boston is vitamin D deficient. I take 1,000 IU per day. Been taking it for years.” Ms. Koehn is the founder and president of Arthritis Consumer Experts, a website that provides education to those with arthritis.
“Agreed. I tell every patient to take vitamin D supplement,” commented Fatma Dedeoglu, MD, a rheumatologist at Boston Children’s Hospital.
A version of this article first appeared on Medscape.com.
FROM ACR 2021
Aspirin lowered preeclampsia risk in real-world lupus study
Women with systemic lupus erythematous (SLE) who are at risk for preeclampsia may benefit from timely treatment with low-dose aspirin and perhaps hydroxychloroquine, according to German researchers.
In a prospective, real-world study of 190 pregnancies in 148 women (average age, 30 years), the use of low-dose aspirin starting around the 16th week of gestation was associated with a lower risk for preeclampsia than was no aspirin use (adjusted odds ratio [aOR], 0.21; P < .05).
The use of hydroxychloroquine starting in the first trimester had a “moderating effect,” said Isabell Haase, MD, a senior clinician scientist in the department of rheumatology at Hiller-Research Unit, Düsseldorf, Germany. Although this was not a statistically significant effect (aOR, 0.47; P = .21), the association strengthened if only high-risk pregnancies were considered (aOR, 0.28; P = .075).
“I think this once more shows us that counseling and risk assessment in our lupus patients is very important to find out those with the highest risk and treat them as good as possible,” Dr. Haase said at an international congress on systemic lupus erythematosus.
Preeclampsia and lupus
“Women with SLE face a high risk of preeclampsia because of their autoimmune disease,” Dr. Haase explained. “This [risk] can be further increased if a woman carries additional risk factors, like hypertension or lupus nephritis.”
Low-dose aspirin is known to protect against the development of preeclampsia in women without autoimmune disease if started before the 16th gestational week of pregnancy, Dr. Haase added. That is why it’s recommended by both the American College of Rheumatology and the European Alliance of Associations for Rheumatology.
“For hydroxychloroquine, we only have some small studies and its mechanism of action that lead us to the idea that it could also have a beneficial effect on preeclampsia in lupus patients,” she said.
Study design and results
The aim of the study was to see in a real-world cohort whether there was any beneficial effect of either aspirin or hydroxychloroquine regarding the development of preeclampsia.
The researchers used prospectively collected data from pregnancies seen at an outpatient pregnancy clinic during 1995-2019. They used multiple logistic regression to determine whether there was any effect of four treatments on the development of preeclampsia: aspirin (n = 39 patients) or hydroxychloroquine (n = 39) alone, in combination (n = 43), or neither drug (n = 69).
Overall, 56% of the women had significant risk factors for preeclampsia, including a prior history, multifetal gestation, chronic hypertension, lupus nephritis, or antiphospholipid antibodies (aPL). A further 28% had moderate risk factors, including not having had children, a body mass index >30 kg/m2, and being older than 35 years.
The overall rate of preeclampsia in the study population was 13.2%, “which is in line with other studies in lupus pregnancies,” Dr. Haase said. Rates in each of the four treatment groups were 15.4% with aspirin alone, 7.7% with hydroxychloroquine alone, 14% with both drugs, and 14.5% with neither.
The odds of developing preeclampsia were lower with both aspirin and hydroxychloroquine. Factors that raised the odds were high disease activity in the first trimester (aOR, 4.55), a BMI of >30 kg/m2 (aOR, 6.14), having high-risk aPL or antiphospholipid syndrome (aOR, 8.02), and a history of preeclampsia (aOR, 9.78).
Only high disease activity in the first trimester and BMI >30 kg/m2 remained independent predictors of preeclampsia when the researchers considered only high-risk pregnancies (aOR, 7.74 for high disease activity in first trimester and 10.04 for a high BMI).
The results are “really impressive,” said Angela Tincani, MD, senior consultant at the Rheumatology and Clinical Immunology Unit of ASST–Spedali Civili di Brescia, in Italy.
Dr. Tincani observed that the study had covered a “large number of years” (1995-2020).
“I think that our attitude in looking after lupus patients [changed] during this time,” she said.
“As an example, I think that we probably use less corticosteroids now than in the 90s,” she said.
When asked whether changes in practices have influenced the findings, she acknowledged, “You can see that the prescription of the different medications has changed a lot. We also thought that we have to take into account the years as a confounder, but we haven’t statistically analyzed that, but it’s definitely something that we are going to do next.”
The study received no outside funding. Dr. Haase has received travel fees from AbbVie, Celgene, Chugai, Janssen-Cilag, Eli Lilly, and Medac. Dr. Tincani has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Women with systemic lupus erythematous (SLE) who are at risk for preeclampsia may benefit from timely treatment with low-dose aspirin and perhaps hydroxychloroquine, according to German researchers.
In a prospective, real-world study of 190 pregnancies in 148 women (average age, 30 years), the use of low-dose aspirin starting around the 16th week of gestation was associated with a lower risk for preeclampsia than was no aspirin use (adjusted odds ratio [aOR], 0.21; P < .05).
The use of hydroxychloroquine starting in the first trimester had a “moderating effect,” said Isabell Haase, MD, a senior clinician scientist in the department of rheumatology at Hiller-Research Unit, Düsseldorf, Germany. Although this was not a statistically significant effect (aOR, 0.47; P = .21), the association strengthened if only high-risk pregnancies were considered (aOR, 0.28; P = .075).
“I think this once more shows us that counseling and risk assessment in our lupus patients is very important to find out those with the highest risk and treat them as good as possible,” Dr. Haase said at an international congress on systemic lupus erythematosus.
Preeclampsia and lupus
“Women with SLE face a high risk of preeclampsia because of their autoimmune disease,” Dr. Haase explained. “This [risk] can be further increased if a woman carries additional risk factors, like hypertension or lupus nephritis.”
Low-dose aspirin is known to protect against the development of preeclampsia in women without autoimmune disease if started before the 16th gestational week of pregnancy, Dr. Haase added. That is why it’s recommended by both the American College of Rheumatology and the European Alliance of Associations for Rheumatology.
“For hydroxychloroquine, we only have some small studies and its mechanism of action that lead us to the idea that it could also have a beneficial effect on preeclampsia in lupus patients,” she said.
Study design and results
The aim of the study was to see in a real-world cohort whether there was any beneficial effect of either aspirin or hydroxychloroquine regarding the development of preeclampsia.
The researchers used prospectively collected data from pregnancies seen at an outpatient pregnancy clinic during 1995-2019. They used multiple logistic regression to determine whether there was any effect of four treatments on the development of preeclampsia: aspirin (n = 39 patients) or hydroxychloroquine (n = 39) alone, in combination (n = 43), or neither drug (n = 69).
Overall, 56% of the women had significant risk factors for preeclampsia, including a prior history, multifetal gestation, chronic hypertension, lupus nephritis, or antiphospholipid antibodies (aPL). A further 28% had moderate risk factors, including not having had children, a body mass index >30 kg/m2, and being older than 35 years.
The overall rate of preeclampsia in the study population was 13.2%, “which is in line with other studies in lupus pregnancies,” Dr. Haase said. Rates in each of the four treatment groups were 15.4% with aspirin alone, 7.7% with hydroxychloroquine alone, 14% with both drugs, and 14.5% with neither.
The odds of developing preeclampsia were lower with both aspirin and hydroxychloroquine. Factors that raised the odds were high disease activity in the first trimester (aOR, 4.55), a BMI of >30 kg/m2 (aOR, 6.14), having high-risk aPL or antiphospholipid syndrome (aOR, 8.02), and a history of preeclampsia (aOR, 9.78).
Only high disease activity in the first trimester and BMI >30 kg/m2 remained independent predictors of preeclampsia when the researchers considered only high-risk pregnancies (aOR, 7.74 for high disease activity in first trimester and 10.04 for a high BMI).
The results are “really impressive,” said Angela Tincani, MD, senior consultant at the Rheumatology and Clinical Immunology Unit of ASST–Spedali Civili di Brescia, in Italy.
Dr. Tincani observed that the study had covered a “large number of years” (1995-2020).
“I think that our attitude in looking after lupus patients [changed] during this time,” she said.
“As an example, I think that we probably use less corticosteroids now than in the 90s,” she said.
When asked whether changes in practices have influenced the findings, she acknowledged, “You can see that the prescription of the different medications has changed a lot. We also thought that we have to take into account the years as a confounder, but we haven’t statistically analyzed that, but it’s definitely something that we are going to do next.”
The study received no outside funding. Dr. Haase has received travel fees from AbbVie, Celgene, Chugai, Janssen-Cilag, Eli Lilly, and Medac. Dr. Tincani has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Women with systemic lupus erythematous (SLE) who are at risk for preeclampsia may benefit from timely treatment with low-dose aspirin and perhaps hydroxychloroquine, according to German researchers.
In a prospective, real-world study of 190 pregnancies in 148 women (average age, 30 years), the use of low-dose aspirin starting around the 16th week of gestation was associated with a lower risk for preeclampsia than was no aspirin use (adjusted odds ratio [aOR], 0.21; P < .05).
The use of hydroxychloroquine starting in the first trimester had a “moderating effect,” said Isabell Haase, MD, a senior clinician scientist in the department of rheumatology at Hiller-Research Unit, Düsseldorf, Germany. Although this was not a statistically significant effect (aOR, 0.47; P = .21), the association strengthened if only high-risk pregnancies were considered (aOR, 0.28; P = .075).
“I think this once more shows us that counseling and risk assessment in our lupus patients is very important to find out those with the highest risk and treat them as good as possible,” Dr. Haase said at an international congress on systemic lupus erythematosus.
Preeclampsia and lupus
“Women with SLE face a high risk of preeclampsia because of their autoimmune disease,” Dr. Haase explained. “This [risk] can be further increased if a woman carries additional risk factors, like hypertension or lupus nephritis.”
Low-dose aspirin is known to protect against the development of preeclampsia in women without autoimmune disease if started before the 16th gestational week of pregnancy, Dr. Haase added. That is why it’s recommended by both the American College of Rheumatology and the European Alliance of Associations for Rheumatology.
“For hydroxychloroquine, we only have some small studies and its mechanism of action that lead us to the idea that it could also have a beneficial effect on preeclampsia in lupus patients,” she said.
Study design and results
The aim of the study was to see in a real-world cohort whether there was any beneficial effect of either aspirin or hydroxychloroquine regarding the development of preeclampsia.
The researchers used prospectively collected data from pregnancies seen at an outpatient pregnancy clinic during 1995-2019. They used multiple logistic regression to determine whether there was any effect of four treatments on the development of preeclampsia: aspirin (n = 39 patients) or hydroxychloroquine (n = 39) alone, in combination (n = 43), or neither drug (n = 69).
Overall, 56% of the women had significant risk factors for preeclampsia, including a prior history, multifetal gestation, chronic hypertension, lupus nephritis, or antiphospholipid antibodies (aPL). A further 28% had moderate risk factors, including not having had children, a body mass index >30 kg/m2, and being older than 35 years.
The overall rate of preeclampsia in the study population was 13.2%, “which is in line with other studies in lupus pregnancies,” Dr. Haase said. Rates in each of the four treatment groups were 15.4% with aspirin alone, 7.7% with hydroxychloroquine alone, 14% with both drugs, and 14.5% with neither.
The odds of developing preeclampsia were lower with both aspirin and hydroxychloroquine. Factors that raised the odds were high disease activity in the first trimester (aOR, 4.55), a BMI of >30 kg/m2 (aOR, 6.14), having high-risk aPL or antiphospholipid syndrome (aOR, 8.02), and a history of preeclampsia (aOR, 9.78).
Only high disease activity in the first trimester and BMI >30 kg/m2 remained independent predictors of preeclampsia when the researchers considered only high-risk pregnancies (aOR, 7.74 for high disease activity in first trimester and 10.04 for a high BMI).
The results are “really impressive,” said Angela Tincani, MD, senior consultant at the Rheumatology and Clinical Immunology Unit of ASST–Spedali Civili di Brescia, in Italy.
Dr. Tincani observed that the study had covered a “large number of years” (1995-2020).
“I think that our attitude in looking after lupus patients [changed] during this time,” she said.
“As an example, I think that we probably use less corticosteroids now than in the 90s,” she said.
When asked whether changes in practices have influenced the findings, she acknowledged, “You can see that the prescription of the different medications has changed a lot. We also thought that we have to take into account the years as a confounder, but we haven’t statistically analyzed that, but it’s definitely something that we are going to do next.”
The study received no outside funding. Dr. Haase has received travel fees from AbbVie, Celgene, Chugai, Janssen-Cilag, Eli Lilly, and Medac. Dr. Tincani has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM LUPUS 2021
‘Multimorbidity’ more commonly seen in people with lupus
People with systemic lupus erythematosus (SLE) have a threefold greater likelihood of having up to five or more comorbidities in comparison with people in the general population, according to the results of two separate U.S. population-based studies.
The higher rate of comorbidities seen included many of those commonly reported before, such as cardiovascular and renal disease, but also some that may be less frequently associated with SLE, notably chronic obstructive pulmonary disease (COPD) and cardiac arrhythmias.
“In the past, the characterization of SLE comorbidities has relied on individual comorbidity assessment,” Alí Duarte García, MD, said at the 14th International Congress on Systemic Lupus Erythematosus, held together will the 6th International Congress on Controversies in Rheumatology and Autoimmunity.
“However, a patient-centric approach where a patient as a whole is seen and how many comorbidities they accrue has not been performed.” added Duarte García, who is a rheumatologist at the Mayo Clinic in Rochester, Minn.
Multiple conditions “overrepresented” in SLE patients
Dr. Duarte García reported the findings of one of the studies, both of which used data from the Rochester Epidemiology Project, a record-linkage system that collates clinical and hospital data from individuals who live in 19 counties in southeast Minnesota and eight counties in western Wisconsin; these patients have agreed to share their medical records for research.
The study population included 479 individuals diagnosed with SLE according to joint 2019 European Alliance of Associations for Rheumatology and American College of Rheumatology criteria. These were matched by age, sex, race, and county to 479 individuals without SLE.
The mean age of the study population was 53 years, 82% were women, and 86% were White.
“We defined multimorbidity as those patients who have two or more comorbidities and substantial multimorbidity as those patients who have five or more comorbidities,” Dr. Duarte García explained.
A previously published list of 44 categories of comorbidities was used to classify the multimorbidity seen, and 27 of these were “overrepresented” in patients with SLE.
Patients with SLE averaged 5.3 comorbidities, whereas control study subjects had 2.9. Comparing SLE with non-SLE individuals, the odds ratio for having two or more comorbid conditions was 2.96, and for five or more comorbidities it was 3.06.
The highest odds ratio comparing SLE with non-SLE individuals was seen for pulmonary disorders (39.0).
Dr. Duarte García highlighted four comorbidities that occurred in SLE patients that were perhaps more unusual: congestive heart failure (OR, 13.3), valvular heart disease (OR, 4.2), cardiac arrhythmias (OR, 2.85), and COPD (OR, 2.7).
“Given the association of multimorbidity with poor outcomes, care delivery strategies to manage multimorbidity are needed in SLE,” Dr. Duarte García concluded.
Similar findings seen in cutaneous lupus
There is also an excess of comorbid conditions in people with cutaneous lupus erythematosus (CLE), Mehmet Hocaoglu, MD, said in reporting the findings of the second study.
Dr. Hocaoglu, an internal medicine resident at the University of Maryland Medical Center in Baltimore, and part of the same team of researchers as Dr. Duarte García, noted that in skin-related lupus the risk of multimorbidity was about doubled.
For this separate analysis, a total of 303 patients with cutaneous lupus had been matched to 303 controls from the general population. Odds ratios for having two or more or five or more comorbidities were a respective 2.27 and 1.65.
Among the comorbidities seen that were higher in those with cutaneous lupus than in the general population subjects were fibromyalgia, liver disease, hypertension, anemia, hypothyroidism, and COPD.
“Further research is definitely needed to identify if the driver of this multimorbidity in CLE patients is the disease itself or the treatments CLE patients are receiving or a multifactorial cause that is driving the disease association,” Dr. Hocaoglu said.
Comment and perspective
“Comorbidities that are not appropriate to the general population, compared to SLE,” seem to have been included in the overall SLE and the cutaneous lupus analyses, Raquel Faria, MD, suggested.
Dr. Faria, an internal medicine consultant at Unidade de Imunologia Clínica – Centro Hospitalar Universitário Porto (Portugal), chaired the poster discussion session in which the two studies had been presented.
She wondered if the researchers had analyzed the data while accounting for “the comorbidities that you knew are due to activity in lupus, like anemia?”
The number of patients with SLE who had pulmonary circulation disorders – 7.5% vs. 0.2% of the general population – also caught Dr. Faria’s attention.
That’s “a really huge number,” Dr. Faria pointed out, “I think it is pretty overrepresented.”
Dr. Duarte García acknowledged that they “took a very broad approach” in using a “very large comorbidity index.”
“What we were observing initially is precisely what you’re mentioning,” he responded to Dr. Faria.
“We were pulling patients who were having disease manifestation rather than a comorbidity,” Dr. Duarte-García said.
These are initial and very exploratory data, he stressed. “We have now moved on to modify the index.” Some of the changes that they have made were to incorporate the SLICC Damage Index Score and tighten up the list of ICD codes used.
No outside funding was received for either of the studies. Dr. Duarte García and Dr. Hocaoglu individually stated that they had no actual or potential conflicts of interest in relation to their presentations.
A version of this article first appeared on Medscape.com.
People with systemic lupus erythematosus (SLE) have a threefold greater likelihood of having up to five or more comorbidities in comparison with people in the general population, according to the results of two separate U.S. population-based studies.
The higher rate of comorbidities seen included many of those commonly reported before, such as cardiovascular and renal disease, but also some that may be less frequently associated with SLE, notably chronic obstructive pulmonary disease (COPD) and cardiac arrhythmias.
“In the past, the characterization of SLE comorbidities has relied on individual comorbidity assessment,” Alí Duarte García, MD, said at the 14th International Congress on Systemic Lupus Erythematosus, held together will the 6th International Congress on Controversies in Rheumatology and Autoimmunity.
“However, a patient-centric approach where a patient as a whole is seen and how many comorbidities they accrue has not been performed.” added Duarte García, who is a rheumatologist at the Mayo Clinic in Rochester, Minn.
Multiple conditions “overrepresented” in SLE patients
Dr. Duarte García reported the findings of one of the studies, both of which used data from the Rochester Epidemiology Project, a record-linkage system that collates clinical and hospital data from individuals who live in 19 counties in southeast Minnesota and eight counties in western Wisconsin; these patients have agreed to share their medical records for research.
The study population included 479 individuals diagnosed with SLE according to joint 2019 European Alliance of Associations for Rheumatology and American College of Rheumatology criteria. These were matched by age, sex, race, and county to 479 individuals without SLE.
The mean age of the study population was 53 years, 82% were women, and 86% were White.
“We defined multimorbidity as those patients who have two or more comorbidities and substantial multimorbidity as those patients who have five or more comorbidities,” Dr. Duarte García explained.
A previously published list of 44 categories of comorbidities was used to classify the multimorbidity seen, and 27 of these were “overrepresented” in patients with SLE.
Patients with SLE averaged 5.3 comorbidities, whereas control study subjects had 2.9. Comparing SLE with non-SLE individuals, the odds ratio for having two or more comorbid conditions was 2.96, and for five or more comorbidities it was 3.06.
The highest odds ratio comparing SLE with non-SLE individuals was seen for pulmonary disorders (39.0).
Dr. Duarte García highlighted four comorbidities that occurred in SLE patients that were perhaps more unusual: congestive heart failure (OR, 13.3), valvular heart disease (OR, 4.2), cardiac arrhythmias (OR, 2.85), and COPD (OR, 2.7).
“Given the association of multimorbidity with poor outcomes, care delivery strategies to manage multimorbidity are needed in SLE,” Dr. Duarte García concluded.
Similar findings seen in cutaneous lupus
There is also an excess of comorbid conditions in people with cutaneous lupus erythematosus (CLE), Mehmet Hocaoglu, MD, said in reporting the findings of the second study.
Dr. Hocaoglu, an internal medicine resident at the University of Maryland Medical Center in Baltimore, and part of the same team of researchers as Dr. Duarte García, noted that in skin-related lupus the risk of multimorbidity was about doubled.
For this separate analysis, a total of 303 patients with cutaneous lupus had been matched to 303 controls from the general population. Odds ratios for having two or more or five or more comorbidities were a respective 2.27 and 1.65.
Among the comorbidities seen that were higher in those with cutaneous lupus than in the general population subjects were fibromyalgia, liver disease, hypertension, anemia, hypothyroidism, and COPD.
“Further research is definitely needed to identify if the driver of this multimorbidity in CLE patients is the disease itself or the treatments CLE patients are receiving or a multifactorial cause that is driving the disease association,” Dr. Hocaoglu said.
Comment and perspective
“Comorbidities that are not appropriate to the general population, compared to SLE,” seem to have been included in the overall SLE and the cutaneous lupus analyses, Raquel Faria, MD, suggested.
Dr. Faria, an internal medicine consultant at Unidade de Imunologia Clínica – Centro Hospitalar Universitário Porto (Portugal), chaired the poster discussion session in which the two studies had been presented.
She wondered if the researchers had analyzed the data while accounting for “the comorbidities that you knew are due to activity in lupus, like anemia?”
The number of patients with SLE who had pulmonary circulation disorders – 7.5% vs. 0.2% of the general population – also caught Dr. Faria’s attention.
That’s “a really huge number,” Dr. Faria pointed out, “I think it is pretty overrepresented.”
Dr. Duarte García acknowledged that they “took a very broad approach” in using a “very large comorbidity index.”
“What we were observing initially is precisely what you’re mentioning,” he responded to Dr. Faria.
“We were pulling patients who were having disease manifestation rather than a comorbidity,” Dr. Duarte-García said.
These are initial and very exploratory data, he stressed. “We have now moved on to modify the index.” Some of the changes that they have made were to incorporate the SLICC Damage Index Score and tighten up the list of ICD codes used.
No outside funding was received for either of the studies. Dr. Duarte García and Dr. Hocaoglu individually stated that they had no actual or potential conflicts of interest in relation to their presentations.
A version of this article first appeared on Medscape.com.
People with systemic lupus erythematosus (SLE) have a threefold greater likelihood of having up to five or more comorbidities in comparison with people in the general population, according to the results of two separate U.S. population-based studies.
The higher rate of comorbidities seen included many of those commonly reported before, such as cardiovascular and renal disease, but also some that may be less frequently associated with SLE, notably chronic obstructive pulmonary disease (COPD) and cardiac arrhythmias.
“In the past, the characterization of SLE comorbidities has relied on individual comorbidity assessment,” Alí Duarte García, MD, said at the 14th International Congress on Systemic Lupus Erythematosus, held together will the 6th International Congress on Controversies in Rheumatology and Autoimmunity.
“However, a patient-centric approach where a patient as a whole is seen and how many comorbidities they accrue has not been performed.” added Duarte García, who is a rheumatologist at the Mayo Clinic in Rochester, Minn.
Multiple conditions “overrepresented” in SLE patients
Dr. Duarte García reported the findings of one of the studies, both of which used data from the Rochester Epidemiology Project, a record-linkage system that collates clinical and hospital data from individuals who live in 19 counties in southeast Minnesota and eight counties in western Wisconsin; these patients have agreed to share their medical records for research.
The study population included 479 individuals diagnosed with SLE according to joint 2019 European Alliance of Associations for Rheumatology and American College of Rheumatology criteria. These were matched by age, sex, race, and county to 479 individuals without SLE.
The mean age of the study population was 53 years, 82% were women, and 86% were White.
“We defined multimorbidity as those patients who have two or more comorbidities and substantial multimorbidity as those patients who have five or more comorbidities,” Dr. Duarte García explained.
A previously published list of 44 categories of comorbidities was used to classify the multimorbidity seen, and 27 of these were “overrepresented” in patients with SLE.
Patients with SLE averaged 5.3 comorbidities, whereas control study subjects had 2.9. Comparing SLE with non-SLE individuals, the odds ratio for having two or more comorbid conditions was 2.96, and for five or more comorbidities it was 3.06.
The highest odds ratio comparing SLE with non-SLE individuals was seen for pulmonary disorders (39.0).
Dr. Duarte García highlighted four comorbidities that occurred in SLE patients that were perhaps more unusual: congestive heart failure (OR, 13.3), valvular heart disease (OR, 4.2), cardiac arrhythmias (OR, 2.85), and COPD (OR, 2.7).
“Given the association of multimorbidity with poor outcomes, care delivery strategies to manage multimorbidity are needed in SLE,” Dr. Duarte García concluded.
Similar findings seen in cutaneous lupus
There is also an excess of comorbid conditions in people with cutaneous lupus erythematosus (CLE), Mehmet Hocaoglu, MD, said in reporting the findings of the second study.
Dr. Hocaoglu, an internal medicine resident at the University of Maryland Medical Center in Baltimore, and part of the same team of researchers as Dr. Duarte García, noted that in skin-related lupus the risk of multimorbidity was about doubled.
For this separate analysis, a total of 303 patients with cutaneous lupus had been matched to 303 controls from the general population. Odds ratios for having two or more or five or more comorbidities were a respective 2.27 and 1.65.
Among the comorbidities seen that were higher in those with cutaneous lupus than in the general population subjects were fibromyalgia, liver disease, hypertension, anemia, hypothyroidism, and COPD.
“Further research is definitely needed to identify if the driver of this multimorbidity in CLE patients is the disease itself or the treatments CLE patients are receiving or a multifactorial cause that is driving the disease association,” Dr. Hocaoglu said.
Comment and perspective
“Comorbidities that are not appropriate to the general population, compared to SLE,” seem to have been included in the overall SLE and the cutaneous lupus analyses, Raquel Faria, MD, suggested.
Dr. Faria, an internal medicine consultant at Unidade de Imunologia Clínica – Centro Hospitalar Universitário Porto (Portugal), chaired the poster discussion session in which the two studies had been presented.
She wondered if the researchers had analyzed the data while accounting for “the comorbidities that you knew are due to activity in lupus, like anemia?”
The number of patients with SLE who had pulmonary circulation disorders – 7.5% vs. 0.2% of the general population – also caught Dr. Faria’s attention.
That’s “a really huge number,” Dr. Faria pointed out, “I think it is pretty overrepresented.”
Dr. Duarte García acknowledged that they “took a very broad approach” in using a “very large comorbidity index.”
“What we were observing initially is precisely what you’re mentioning,” he responded to Dr. Faria.
“We were pulling patients who were having disease manifestation rather than a comorbidity,” Dr. Duarte-García said.
These are initial and very exploratory data, he stressed. “We have now moved on to modify the index.” Some of the changes that they have made were to incorporate the SLICC Damage Index Score and tighten up the list of ICD codes used.
No outside funding was received for either of the studies. Dr. Duarte García and Dr. Hocaoglu individually stated that they had no actual or potential conflicts of interest in relation to their presentations.
A version of this article first appeared on Medscape.com.
U.S. arthritis prevalence continues steady rise; activity limitations grow more rapidly
Nearly a quarter of adults in the United States have been diagnosed with various forms of arthritis, new federal estimates report. The disorders limit the activities of 43.9% of them. Researchers also report that adults with poorer mental or physical health and those who are more disadvantaged socially are most vulnerable to arthritis.
“There is a substantial unmet need for existing, evidence-based, arthritis-appropriate interventions for people with arthritis to minimize activity limitations,” study coauthor and Centers for Disease Control and Prevention epidemiologist Kristina Theis, PhD, MPH, told this news organization. “Our findings show that interventions addressing self-management, education, physical activity, workplace accommodations, and mental health, among other areas, are all indicated for people with arthritis.”
The CDC report was published Oct. 8 in Morbidity and Mortality Weekly Report. Researchers estimated the number of arthritis cases on the basis of in-person interviews conducted with tens of thousands of U.S. adults as part of the National Health Interview Survey during 2016-2018. In the report, the researchers considered arthritis to include general arthritis, rheumatoid arthritis, gout, lupus, and fibromyalgia.
Activity limitations rose faster than predicted
According to the report, an estimated 58.5 million U.S. adults (23.7%; 21.5% age-standardized) told interviewers that they had been diagnosed with arthritis conditions. Of those, 25.7 million (43.9%; 40.8% age-standardized) had arthritis-attributable activity limitations (AAALs), which represents 10.4% of all adults.
The number of adults who reported having arthritis rose by 4.1 million from previous estimates for the years 2013-2015, a number that’s on pace with predictions. The number in the AAAL category rose by 2 million, a jump that’s higher than what had been predicted.
“The aging of the population is one factor in the increasing number of people with arthritis, even though arthritis is not an inevitable part of aging,” Dr. Theis said. “Individual factors, such as body mass index or other health conditions, and societal factors, such as educational and economic opportunities, likely play a role.”
Arthritis was especially common among those aged ≥ 65 years (50.4%), those who were unable to work or were disabled (52.3%), and those who self-reported fair/poor health (51.2%) or joint symptoms in the past 30 days (52.2%). The rate of arthritis was also high among those whose activities of daily living (ADL) were limited (54.8%) and those whose instrumental activities of daily living (IADL) were limited (55.9%).
The researchers report that the percentage of AAAL was also high among the following groups: “adults with joint symptoms in the past 30 days (51.6%), adults who were unable to work or disabled (54.7%), adults of other/multiple races (54.5%) or non-Hispanic American Indian or Alaska Natives (60.7%), adults with low income (53.3%) or poor/near poor income-to-poverty ratios (63.3%), or with moderate psychological distress (59.5%). AAAL was reported by a high proportion of adults with arthritis who had an ADL disability (82.6%), IADL disability (80.4%), serious psychological distress (76.3%), or fair/poor self-rated health (72.6%).”
The researchers found that among all adults with arthritis, the percentage of adults with arthritis was high among women (59.3%), those with obesity or overweight (74.2%), and those who weren’t sufficiently active (58%).
Comments on latest findings
Michael LaValley, PhD, biostatistician at the Boston University School of Public Health, who has studied arthritis statistics, told this news organization that the findings “fall right in line with the trends that have been observed in arthritis over the past 20 years. The prevalence is increasing, which certainly seems to be influenced by the aging population in the U.S.”
As for specific conditions, he said the rate of osteoarthritis may be influenced by older Americans and by those with obesity and sedentary behavior. “There is also some thinking that there may be environmental factors increasing the risk for some types of arthritis, but nothing conclusive. There also may be more clinical attention paid to arthritic conditions, leading to more people being diagnosed or even just suspecting that they have arthritis.”
It’s difficult to disentangle connections between arthritis and risk factors such as poverty, he said. “There almost certainly are occupational exposures that put people at risk of osteoarthritis – having to kneel, stoop, and lift heavy things – or other musculoskeletal conditions like lower back pain. These exposures are most likely in jobs that would predominantly go to people with few other options because of lower levels of income and education. People in these jobs would also be more likely to have financial stresses that lead to increased psychological distress and less time to take care of their health.”
Also, he said, “There is probably some reverse causation with the occupational results, self-related health, and psychological distress. These could all be affected by a person’s arthritis. Having arthritis may interfere with getting a better-paying job, and arthritis could certainly reduce someone’s self-reported health and induce psychological distress.”
The authors and LaValley have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Nearly a quarter of adults in the United States have been diagnosed with various forms of arthritis, new federal estimates report. The disorders limit the activities of 43.9% of them. Researchers also report that adults with poorer mental or physical health and those who are more disadvantaged socially are most vulnerable to arthritis.
“There is a substantial unmet need for existing, evidence-based, arthritis-appropriate interventions for people with arthritis to minimize activity limitations,” study coauthor and Centers for Disease Control and Prevention epidemiologist Kristina Theis, PhD, MPH, told this news organization. “Our findings show that interventions addressing self-management, education, physical activity, workplace accommodations, and mental health, among other areas, are all indicated for people with arthritis.”
The CDC report was published Oct. 8 in Morbidity and Mortality Weekly Report. Researchers estimated the number of arthritis cases on the basis of in-person interviews conducted with tens of thousands of U.S. adults as part of the National Health Interview Survey during 2016-2018. In the report, the researchers considered arthritis to include general arthritis, rheumatoid arthritis, gout, lupus, and fibromyalgia.
Activity limitations rose faster than predicted
According to the report, an estimated 58.5 million U.S. adults (23.7%; 21.5% age-standardized) told interviewers that they had been diagnosed with arthritis conditions. Of those, 25.7 million (43.9%; 40.8% age-standardized) had arthritis-attributable activity limitations (AAALs), which represents 10.4% of all adults.
The number of adults who reported having arthritis rose by 4.1 million from previous estimates for the years 2013-2015, a number that’s on pace with predictions. The number in the AAAL category rose by 2 million, a jump that’s higher than what had been predicted.
“The aging of the population is one factor in the increasing number of people with arthritis, even though arthritis is not an inevitable part of aging,” Dr. Theis said. “Individual factors, such as body mass index or other health conditions, and societal factors, such as educational and economic opportunities, likely play a role.”
Arthritis was especially common among those aged ≥ 65 years (50.4%), those who were unable to work or were disabled (52.3%), and those who self-reported fair/poor health (51.2%) or joint symptoms in the past 30 days (52.2%). The rate of arthritis was also high among those whose activities of daily living (ADL) were limited (54.8%) and those whose instrumental activities of daily living (IADL) were limited (55.9%).
The researchers report that the percentage of AAAL was also high among the following groups: “adults with joint symptoms in the past 30 days (51.6%), adults who were unable to work or disabled (54.7%), adults of other/multiple races (54.5%) or non-Hispanic American Indian or Alaska Natives (60.7%), adults with low income (53.3%) or poor/near poor income-to-poverty ratios (63.3%), or with moderate psychological distress (59.5%). AAAL was reported by a high proportion of adults with arthritis who had an ADL disability (82.6%), IADL disability (80.4%), serious psychological distress (76.3%), or fair/poor self-rated health (72.6%).”
The researchers found that among all adults with arthritis, the percentage of adults with arthritis was high among women (59.3%), those with obesity or overweight (74.2%), and those who weren’t sufficiently active (58%).
Comments on latest findings
Michael LaValley, PhD, biostatistician at the Boston University School of Public Health, who has studied arthritis statistics, told this news organization that the findings “fall right in line with the trends that have been observed in arthritis over the past 20 years. The prevalence is increasing, which certainly seems to be influenced by the aging population in the U.S.”
As for specific conditions, he said the rate of osteoarthritis may be influenced by older Americans and by those with obesity and sedentary behavior. “There is also some thinking that there may be environmental factors increasing the risk for some types of arthritis, but nothing conclusive. There also may be more clinical attention paid to arthritic conditions, leading to more people being diagnosed or even just suspecting that they have arthritis.”
It’s difficult to disentangle connections between arthritis and risk factors such as poverty, he said. “There almost certainly are occupational exposures that put people at risk of osteoarthritis – having to kneel, stoop, and lift heavy things – or other musculoskeletal conditions like lower back pain. These exposures are most likely in jobs that would predominantly go to people with few other options because of lower levels of income and education. People in these jobs would also be more likely to have financial stresses that lead to increased psychological distress and less time to take care of their health.”
Also, he said, “There is probably some reverse causation with the occupational results, self-related health, and psychological distress. These could all be affected by a person’s arthritis. Having arthritis may interfere with getting a better-paying job, and arthritis could certainly reduce someone’s self-reported health and induce psychological distress.”
The authors and LaValley have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Nearly a quarter of adults in the United States have been diagnosed with various forms of arthritis, new federal estimates report. The disorders limit the activities of 43.9% of them. Researchers also report that adults with poorer mental or physical health and those who are more disadvantaged socially are most vulnerable to arthritis.
“There is a substantial unmet need for existing, evidence-based, arthritis-appropriate interventions for people with arthritis to minimize activity limitations,” study coauthor and Centers for Disease Control and Prevention epidemiologist Kristina Theis, PhD, MPH, told this news organization. “Our findings show that interventions addressing self-management, education, physical activity, workplace accommodations, and mental health, among other areas, are all indicated for people with arthritis.”
The CDC report was published Oct. 8 in Morbidity and Mortality Weekly Report. Researchers estimated the number of arthritis cases on the basis of in-person interviews conducted with tens of thousands of U.S. adults as part of the National Health Interview Survey during 2016-2018. In the report, the researchers considered arthritis to include general arthritis, rheumatoid arthritis, gout, lupus, and fibromyalgia.
Activity limitations rose faster than predicted
According to the report, an estimated 58.5 million U.S. adults (23.7%; 21.5% age-standardized) told interviewers that they had been diagnosed with arthritis conditions. Of those, 25.7 million (43.9%; 40.8% age-standardized) had arthritis-attributable activity limitations (AAALs), which represents 10.4% of all adults.
The number of adults who reported having arthritis rose by 4.1 million from previous estimates for the years 2013-2015, a number that’s on pace with predictions. The number in the AAAL category rose by 2 million, a jump that’s higher than what had been predicted.
“The aging of the population is one factor in the increasing number of people with arthritis, even though arthritis is not an inevitable part of aging,” Dr. Theis said. “Individual factors, such as body mass index or other health conditions, and societal factors, such as educational and economic opportunities, likely play a role.”
Arthritis was especially common among those aged ≥ 65 years (50.4%), those who were unable to work or were disabled (52.3%), and those who self-reported fair/poor health (51.2%) or joint symptoms in the past 30 days (52.2%). The rate of arthritis was also high among those whose activities of daily living (ADL) were limited (54.8%) and those whose instrumental activities of daily living (IADL) were limited (55.9%).
The researchers report that the percentage of AAAL was also high among the following groups: “adults with joint symptoms in the past 30 days (51.6%), adults who were unable to work or disabled (54.7%), adults of other/multiple races (54.5%) or non-Hispanic American Indian or Alaska Natives (60.7%), adults with low income (53.3%) or poor/near poor income-to-poverty ratios (63.3%), or with moderate psychological distress (59.5%). AAAL was reported by a high proportion of adults with arthritis who had an ADL disability (82.6%), IADL disability (80.4%), serious psychological distress (76.3%), or fair/poor self-rated health (72.6%).”
The researchers found that among all adults with arthritis, the percentage of adults with arthritis was high among women (59.3%), those with obesity or overweight (74.2%), and those who weren’t sufficiently active (58%).
Comments on latest findings
Michael LaValley, PhD, biostatistician at the Boston University School of Public Health, who has studied arthritis statistics, told this news organization that the findings “fall right in line with the trends that have been observed in arthritis over the past 20 years. The prevalence is increasing, which certainly seems to be influenced by the aging population in the U.S.”
As for specific conditions, he said the rate of osteoarthritis may be influenced by older Americans and by those with obesity and sedentary behavior. “There is also some thinking that there may be environmental factors increasing the risk for some types of arthritis, but nothing conclusive. There also may be more clinical attention paid to arthritic conditions, leading to more people being diagnosed or even just suspecting that they have arthritis.”
It’s difficult to disentangle connections between arthritis and risk factors such as poverty, he said. “There almost certainly are occupational exposures that put people at risk of osteoarthritis – having to kneel, stoop, and lift heavy things – or other musculoskeletal conditions like lower back pain. These exposures are most likely in jobs that would predominantly go to people with few other options because of lower levels of income and education. People in these jobs would also be more likely to have financial stresses that lead to increased psychological distress and less time to take care of their health.”
Also, he said, “There is probably some reverse causation with the occupational results, self-related health, and psychological distress. These could all be affected by a person’s arthritis. Having arthritis may interfere with getting a better-paying job, and arthritis could certainly reduce someone’s self-reported health and induce psychological distress.”
The authors and LaValley have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Adalimumab biosimilar Cyltezo gets interchangeability designation
The Food and Drug Administration approved a supplement to the biologics license application of the adalimumab biosimilar drug Cyltezo (adalimumab-adbm) that makes it the first interchangeable biosimilar with Humira (adalimumab), the original branded version of the drug, its manufacturer Boehringer Ingelheim announced Oct. 15.
The FDA originally approved Cyltezo in 2017 for the treatment of multiple chronic inflammatory diseases, including seven of Humira’s nine indications for adults and pediatric patients: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis.
The interchangeability designation means that Cyltezo was tested in an additional clinical trial in which patients were successfully switched back and forth multiple times from Humira to Cyltezo and allows pharmacists to autosubstitute Humira with Cyltezo. In these cases, individual state laws control how and whether physicians will be notified of this switch.
Cyltezo is just the second biosimilar to be designated as interchangeable with its originator biologic product. The first approval, announced July 28, was for the interchangeability of Semglee (insulin glargine-yfgn) with the originator Lantus.
The agency based its decision on positive data from the VOLTAIRE-X study of 238 patients with moderate to severe chronic plaque psoriasis in which Cyltezo had no meaningful clinical differences from Humira in pharmacokinetics, efficacy, immunogenicity, and safety between the switching and continuous treatment groups.
Cyltezo will not be commercially available in the United States until July 1, 2023, according to Boehringer Ingelheim.
The Food and Drug Administration approved a supplement to the biologics license application of the adalimumab biosimilar drug Cyltezo (adalimumab-adbm) that makes it the first interchangeable biosimilar with Humira (adalimumab), the original branded version of the drug, its manufacturer Boehringer Ingelheim announced Oct. 15.
The FDA originally approved Cyltezo in 2017 for the treatment of multiple chronic inflammatory diseases, including seven of Humira’s nine indications for adults and pediatric patients: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis.
The interchangeability designation means that Cyltezo was tested in an additional clinical trial in which patients were successfully switched back and forth multiple times from Humira to Cyltezo and allows pharmacists to autosubstitute Humira with Cyltezo. In these cases, individual state laws control how and whether physicians will be notified of this switch.
Cyltezo is just the second biosimilar to be designated as interchangeable with its originator biologic product. The first approval, announced July 28, was for the interchangeability of Semglee (insulin glargine-yfgn) with the originator Lantus.
The agency based its decision on positive data from the VOLTAIRE-X study of 238 patients with moderate to severe chronic plaque psoriasis in which Cyltezo had no meaningful clinical differences from Humira in pharmacokinetics, efficacy, immunogenicity, and safety between the switching and continuous treatment groups.
Cyltezo will not be commercially available in the United States until July 1, 2023, according to Boehringer Ingelheim.
The Food and Drug Administration approved a supplement to the biologics license application of the adalimumab biosimilar drug Cyltezo (adalimumab-adbm) that makes it the first interchangeable biosimilar with Humira (adalimumab), the original branded version of the drug, its manufacturer Boehringer Ingelheim announced Oct. 15.
The FDA originally approved Cyltezo in 2017 for the treatment of multiple chronic inflammatory diseases, including seven of Humira’s nine indications for adults and pediatric patients: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis.
The interchangeability designation means that Cyltezo was tested in an additional clinical trial in which patients were successfully switched back and forth multiple times from Humira to Cyltezo and allows pharmacists to autosubstitute Humira with Cyltezo. In these cases, individual state laws control how and whether physicians will be notified of this switch.
Cyltezo is just the second biosimilar to be designated as interchangeable with its originator biologic product. The first approval, announced July 28, was for the interchangeability of Semglee (insulin glargine-yfgn) with the originator Lantus.
The agency based its decision on positive data from the VOLTAIRE-X study of 238 patients with moderate to severe chronic plaque psoriasis in which Cyltezo had no meaningful clinical differences from Humira in pharmacokinetics, efficacy, immunogenicity, and safety between the switching and continuous treatment groups.
Cyltezo will not be commercially available in the United States until July 1, 2023, according to Boehringer Ingelheim.
Lupus may confer higher risk of death from COVID-19
There is a significantly increased risk for acute respiratory distress syndrome (ARDS)–related death from COVID-19 among people with systemic lupus erythematous (SLE), compared with the general population, according to data collected in Brazil in 2020.
“Special care is therefore necessary for these patients, as well as reinforcement of the importance of preventive measures during a pandemic for this population,” said Eloisa Bonfá, MD, PhD, at the 14th International Congress on Systemic Lupus Erythematosus, which was held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.
“We know that lupus patients have an increased susceptibility to infections due to autoimmune dysregulation and use of immunosuppressive therapy,” explained Dr. Bonfá, who is clinical director of the largest tertiary referral center for autoimmune rheumatic diseases in Latin America, the University of São Paulo Faculty of Medicine Hospital Clinics.
“Our study demonstrates for the first time that lupus patients have an increased ARDS severity,” she added.
Prior to the meeting, the study was published in ACR Open Rheumatology.
Collating the evidence
Since the COVID-19 pandemic began, there have been more than 20 million confirmed cases of SARS-CoV-2 infection in Brazil and more than half a million deaths.
Dr. Bonfá presented the results of a cross-sectional study that was part of the country’s national Influenza Epidemiological Reporting Surveillance System. Data from 2020 were used, which included just over 252,000 individuals who had polymerase chain reaction–confirmed SARS-CoV-2 infection. Of these individuals, there were 319 consecutively recruited patients with SLE.
The aim was to look at the effect of being hospitalized for COVID-19–related ARDS on outcomes in people with SLE versus the general population.
ARDS was defined as a positive polymerase chain reaction test and accompanying flu-like symptoms with dyspnea, respiratory discomfort, persistent pressure in the chest, or desaturation less than 95% in room air or having a bluish tinge to the lips or face.
Other telling signs of a serious respiratory infection that were evaluated, but not mandatory for study eligibility, were loss of smell, impaired taste, typical CT findings, or having had contact with a confirmed COVID-19 case in the preceding 2 weeks.
Key findings
The risk for death from COVID-19–related ARDS was “more than double” in patients with SLE, compared with the general population, Dr. Bonfá reported. The relative risk in the fully adjusted, propensity-scored analysis was approximately 2.25.
That analysis did not account for other comorbidities but was fully adjusted for individuals’ age, sex, and region of Brazil where they lived. The latter was important, Dr. Bonfá said, because “we have a high disparity regarding health access and treatment among regions.”
Comorbidities considered as part of the analyses included arterial hypertension, diabetes, malignancies, neurologic disease, and diseases affecting the heart, lung, liver, and kidneys. Researchers also adjusted for smoking, alcohol intake, body weight, pregnancy, and transplantation.
SLE had a greater impact on individuals’ outcomes than all other comorbidities considered.
“We evaluated lupus as one comorbidity compared to all other comorbidities,” Dr. Bonfá explained.
SLE “more than doubled the chances” of dying from ARDS, she said. “This is [a] very impressive finding.”
They found that SLE was associated with an RR for death of 1.73, compared with non-SLE patients, when propensity-score matching without adjustment for comorbidities was used. The RR for death dropped to 1.40 but was still significant when researchers included comorbidities.
Dr. Bonfá and her team also looked at a combined endpoint of death, ICU admission, and need for mechanical ventilation. They found an increased risk in patients with SLE versus the general population in all their analyses, ranging from 1.70 if comorbidities were included in the model to 1.27 if they weren’t to 1.39 if propensity-score matching alone was used.
Got lupus? ‘Get vaccinated’
“The data we have are in nonvaccinated patients,” Dr. Bonfá said. “We didn’t have vaccines in 2020.”
Whether being vaccinated might make a different to the risks found in this study is an “interesting question,” and one that may be examined in the future.
Certainly, other work Dr. Bonfá has been involved in seems to point to a likely benefit of vaccination in patients with autoimmune diseases in terms of reducing mortality from COVID-19, even when rates of infection may be on the rise.
“There’s considerable vaccine hesitancy in SLE patients,” Chi-Chiu Mok, MD, of Tuen Mun Hospital in Hong Kong, observed in a separate presentation at the congress.
This may be for several reasons, such as worry that their disease may flare or the vaccine might compromise their drug treatment or result in uncommon complications.
However, “we should encourage our SLE patients to receive COVID-19 vaccination at a time of clinical remission or low disease activity state,” Dr. Mok advised.
“Physical distancing, protective masks, and personal hygiene [measures]” should also continue.
The bottom line for those with SLE is to get vaccinated, stressed Sandra Navarra, MD, of the University of Santo Tomas Hospital in Manila, the Philippines, during the discussion.
“There’s still so much out there that we do not know about,” she said. “Just get yourself vaccinated.”
The study had no outside funding. Dr. Bonfá, Dr. Mok, and Dr. Navarra reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
There is a significantly increased risk for acute respiratory distress syndrome (ARDS)–related death from COVID-19 among people with systemic lupus erythematous (SLE), compared with the general population, according to data collected in Brazil in 2020.
“Special care is therefore necessary for these patients, as well as reinforcement of the importance of preventive measures during a pandemic for this population,” said Eloisa Bonfá, MD, PhD, at the 14th International Congress on Systemic Lupus Erythematosus, which was held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.
“We know that lupus patients have an increased susceptibility to infections due to autoimmune dysregulation and use of immunosuppressive therapy,” explained Dr. Bonfá, who is clinical director of the largest tertiary referral center for autoimmune rheumatic diseases in Latin America, the University of São Paulo Faculty of Medicine Hospital Clinics.
“Our study demonstrates for the first time that lupus patients have an increased ARDS severity,” she added.
Prior to the meeting, the study was published in ACR Open Rheumatology.
Collating the evidence
Since the COVID-19 pandemic began, there have been more than 20 million confirmed cases of SARS-CoV-2 infection in Brazil and more than half a million deaths.
Dr. Bonfá presented the results of a cross-sectional study that was part of the country’s national Influenza Epidemiological Reporting Surveillance System. Data from 2020 were used, which included just over 252,000 individuals who had polymerase chain reaction–confirmed SARS-CoV-2 infection. Of these individuals, there were 319 consecutively recruited patients with SLE.
The aim was to look at the effect of being hospitalized for COVID-19–related ARDS on outcomes in people with SLE versus the general population.
ARDS was defined as a positive polymerase chain reaction test and accompanying flu-like symptoms with dyspnea, respiratory discomfort, persistent pressure in the chest, or desaturation less than 95% in room air or having a bluish tinge to the lips or face.
Other telling signs of a serious respiratory infection that were evaluated, but not mandatory for study eligibility, were loss of smell, impaired taste, typical CT findings, or having had contact with a confirmed COVID-19 case in the preceding 2 weeks.
Key findings
The risk for death from COVID-19–related ARDS was “more than double” in patients with SLE, compared with the general population, Dr. Bonfá reported. The relative risk in the fully adjusted, propensity-scored analysis was approximately 2.25.
That analysis did not account for other comorbidities but was fully adjusted for individuals’ age, sex, and region of Brazil where they lived. The latter was important, Dr. Bonfá said, because “we have a high disparity regarding health access and treatment among regions.”
Comorbidities considered as part of the analyses included arterial hypertension, diabetes, malignancies, neurologic disease, and diseases affecting the heart, lung, liver, and kidneys. Researchers also adjusted for smoking, alcohol intake, body weight, pregnancy, and transplantation.
SLE had a greater impact on individuals’ outcomes than all other comorbidities considered.
“We evaluated lupus as one comorbidity compared to all other comorbidities,” Dr. Bonfá explained.
SLE “more than doubled the chances” of dying from ARDS, she said. “This is [a] very impressive finding.”
They found that SLE was associated with an RR for death of 1.73, compared with non-SLE patients, when propensity-score matching without adjustment for comorbidities was used. The RR for death dropped to 1.40 but was still significant when researchers included comorbidities.
Dr. Bonfá and her team also looked at a combined endpoint of death, ICU admission, and need for mechanical ventilation. They found an increased risk in patients with SLE versus the general population in all their analyses, ranging from 1.70 if comorbidities were included in the model to 1.27 if they weren’t to 1.39 if propensity-score matching alone was used.
Got lupus? ‘Get vaccinated’
“The data we have are in nonvaccinated patients,” Dr. Bonfá said. “We didn’t have vaccines in 2020.”
Whether being vaccinated might make a different to the risks found in this study is an “interesting question,” and one that may be examined in the future.
Certainly, other work Dr. Bonfá has been involved in seems to point to a likely benefit of vaccination in patients with autoimmune diseases in terms of reducing mortality from COVID-19, even when rates of infection may be on the rise.
“There’s considerable vaccine hesitancy in SLE patients,” Chi-Chiu Mok, MD, of Tuen Mun Hospital in Hong Kong, observed in a separate presentation at the congress.
This may be for several reasons, such as worry that their disease may flare or the vaccine might compromise their drug treatment or result in uncommon complications.
However, “we should encourage our SLE patients to receive COVID-19 vaccination at a time of clinical remission or low disease activity state,” Dr. Mok advised.
“Physical distancing, protective masks, and personal hygiene [measures]” should also continue.
The bottom line for those with SLE is to get vaccinated, stressed Sandra Navarra, MD, of the University of Santo Tomas Hospital in Manila, the Philippines, during the discussion.
“There’s still so much out there that we do not know about,” she said. “Just get yourself vaccinated.”
The study had no outside funding. Dr. Bonfá, Dr. Mok, and Dr. Navarra reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
There is a significantly increased risk for acute respiratory distress syndrome (ARDS)–related death from COVID-19 among people with systemic lupus erythematous (SLE), compared with the general population, according to data collected in Brazil in 2020.
“Special care is therefore necessary for these patients, as well as reinforcement of the importance of preventive measures during a pandemic for this population,” said Eloisa Bonfá, MD, PhD, at the 14th International Congress on Systemic Lupus Erythematosus, which was held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.
“We know that lupus patients have an increased susceptibility to infections due to autoimmune dysregulation and use of immunosuppressive therapy,” explained Dr. Bonfá, who is clinical director of the largest tertiary referral center for autoimmune rheumatic diseases in Latin America, the University of São Paulo Faculty of Medicine Hospital Clinics.
“Our study demonstrates for the first time that lupus patients have an increased ARDS severity,” she added.
Prior to the meeting, the study was published in ACR Open Rheumatology.
Collating the evidence
Since the COVID-19 pandemic began, there have been more than 20 million confirmed cases of SARS-CoV-2 infection in Brazil and more than half a million deaths.
Dr. Bonfá presented the results of a cross-sectional study that was part of the country’s national Influenza Epidemiological Reporting Surveillance System. Data from 2020 were used, which included just over 252,000 individuals who had polymerase chain reaction–confirmed SARS-CoV-2 infection. Of these individuals, there were 319 consecutively recruited patients with SLE.
The aim was to look at the effect of being hospitalized for COVID-19–related ARDS on outcomes in people with SLE versus the general population.
ARDS was defined as a positive polymerase chain reaction test and accompanying flu-like symptoms with dyspnea, respiratory discomfort, persistent pressure in the chest, or desaturation less than 95% in room air or having a bluish tinge to the lips or face.
Other telling signs of a serious respiratory infection that were evaluated, but not mandatory for study eligibility, were loss of smell, impaired taste, typical CT findings, or having had contact with a confirmed COVID-19 case in the preceding 2 weeks.
Key findings
The risk for death from COVID-19–related ARDS was “more than double” in patients with SLE, compared with the general population, Dr. Bonfá reported. The relative risk in the fully adjusted, propensity-scored analysis was approximately 2.25.
That analysis did not account for other comorbidities but was fully adjusted for individuals’ age, sex, and region of Brazil where they lived. The latter was important, Dr. Bonfá said, because “we have a high disparity regarding health access and treatment among regions.”
Comorbidities considered as part of the analyses included arterial hypertension, diabetes, malignancies, neurologic disease, and diseases affecting the heart, lung, liver, and kidneys. Researchers also adjusted for smoking, alcohol intake, body weight, pregnancy, and transplantation.
SLE had a greater impact on individuals’ outcomes than all other comorbidities considered.
“We evaluated lupus as one comorbidity compared to all other comorbidities,” Dr. Bonfá explained.
SLE “more than doubled the chances” of dying from ARDS, she said. “This is [a] very impressive finding.”
They found that SLE was associated with an RR for death of 1.73, compared with non-SLE patients, when propensity-score matching without adjustment for comorbidities was used. The RR for death dropped to 1.40 but was still significant when researchers included comorbidities.
Dr. Bonfá and her team also looked at a combined endpoint of death, ICU admission, and need for mechanical ventilation. They found an increased risk in patients with SLE versus the general population in all their analyses, ranging from 1.70 if comorbidities were included in the model to 1.27 if they weren’t to 1.39 if propensity-score matching alone was used.
Got lupus? ‘Get vaccinated’
“The data we have are in nonvaccinated patients,” Dr. Bonfá said. “We didn’t have vaccines in 2020.”
Whether being vaccinated might make a different to the risks found in this study is an “interesting question,” and one that may be examined in the future.
Certainly, other work Dr. Bonfá has been involved in seems to point to a likely benefit of vaccination in patients with autoimmune diseases in terms of reducing mortality from COVID-19, even when rates of infection may be on the rise.
“There’s considerable vaccine hesitancy in SLE patients,” Chi-Chiu Mok, MD, of Tuen Mun Hospital in Hong Kong, observed in a separate presentation at the congress.
This may be for several reasons, such as worry that their disease may flare or the vaccine might compromise their drug treatment or result in uncommon complications.
However, “we should encourage our SLE patients to receive COVID-19 vaccination at a time of clinical remission or low disease activity state,” Dr. Mok advised.
“Physical distancing, protective masks, and personal hygiene [measures]” should also continue.
The bottom line for those with SLE is to get vaccinated, stressed Sandra Navarra, MD, of the University of Santo Tomas Hospital in Manila, the Philippines, during the discussion.
“There’s still so much out there that we do not know about,” she said. “Just get yourself vaccinated.”
The study had no outside funding. Dr. Bonfá, Dr. Mok, and Dr. Navarra reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Low preconception complement levels linked to adverse pregnancy outcomes in antiphospholipid syndrome
Low serum levels of two complement proteins are linked to worse pregnancy outcomes in women with antiphospholipid syndrome (APS), the results of a multicenter study appear to confirm.
The study evaluated preconception complement levels in 260 pregnancies in 197 women who had APS or carried antiphospholipid antibodies (aPL), and found that low levels of C3 and C4 in the 6 months prior to pregnancy were associated with several gestational complications and resulted in pregnancy losses.
“This study has validated, on large scale, the possible utility of preconception measurement of C3 and C4 levels to predict pregnancy loss in patients with aPL, even at a high-risk profile,” said study investigator Daniele Lini, MD, of ASST Spedali Civili and the University of Brescia (Italy).
“The tests are easy and cheap to be routinely performed, and they could therefore represent a valid aid to identify women that need particular monitoring and management,” he said at the 14th International Congress on Systemic Lupus Erythematosus held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.
aPL and adverse obstetric outcomes
aPL, which include lupus anticoagulant, anti–beta2-glycoprotein 1, and anticardiolipin antibodies, have been shown to induce fetal loss in animal models. Their influence on the outcome of human pregnancies, however, has been less clear, with several studies failing to prove a link between their presence and obstetric complications.
Dr. Lini and coinvestigators conducted a multicenter study involving 11 Italian centers and one Russian center, retrospectively looking for women with primary APS or women who had persistently high levels of aPL but no symptoms who had become pregnant. Of 503 pregnancies, information on complement levels before conception was available for 260, of which 184 had occurred in women with APS and 76 in women with persistently high aPL.
The pregnancies were grouped according to whether there were low (n = 93) or normal (n = 167) levels of C3 and C4 in the last 6 months.
“Women with adverse pregnancy outcomes showed significantly lower preconception complement levels than those with successful pregnancies, without any difference between APS and aPL carriers,” Dr. Lini reported.
Comparing those with low to those with high complement levels, the preterm live birth rate (before 37 weeks’ gestation) was 37% versus 18% (P < .0001).
The full-term live birth rates were a respective 42% and 72% (P < .0001).
The rate of pregnancy loss, which included both abortion and miscarriage, was a respective 21% and 10% (P = .008).
A subgroup analysis focusing on where there was triple aPL positivity found that preconception low C3 and/or C4 levels was associated with an increased rate of pregnancy loss (P = .05). This association disappeared if there was just one or two aPL present.
The researchers found no correlation between complement levels and rates of venous thromboembolism or thrombocytopenia.
Study highlights ‘impact and importance’ of complement in APS
The study indicates “the impact and the importance of complement” in APS, said Yehuda Shoenfeld, MD, the founder and head of the Zabludowicz Center for Autoimmune Diseases at the Sheba Medical Center in Tel Hashomer, Israel.
In the early days of understanding APS, said Dr. Shoenfeld, it was thought that complement was not as important as it was in systemic lupus erythematosus (SLE). The importance of raised complement seen in studies of APS would often be discounted or neglected in comparison to SLE.
However, “slowly, slowly” it has been found that “complement [in APS] is activated very similarly to SLE,” Dr. Shoenfeld noted.
“I think that it’s important to assess the component levels,” Dr. Lini said in discussion. “This is needed to be done in the preconception counseling for APS and aPL carrier patients.”
Determining whether there is single, double, or even triple aPL positivity could be useful in guiding clinical decisions.
“If we have triple positivity, that could mean that there may be a more immunologic activation of the system and that it could be useful to administrate hydroxychloroquine [to] those patients who would like to have a pregnancy,” Dr. Lini suggested.
Plus, in those with decreased complement levels, “this could be a very useful tool” to identify where something could go wrong during their pregnancy.
The study had no outside funding. Dr. Lini and Dr. Shoenfeld disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Low serum levels of two complement proteins are linked to worse pregnancy outcomes in women with antiphospholipid syndrome (APS), the results of a multicenter study appear to confirm.
The study evaluated preconception complement levels in 260 pregnancies in 197 women who had APS or carried antiphospholipid antibodies (aPL), and found that low levels of C3 and C4 in the 6 months prior to pregnancy were associated with several gestational complications and resulted in pregnancy losses.
“This study has validated, on large scale, the possible utility of preconception measurement of C3 and C4 levels to predict pregnancy loss in patients with aPL, even at a high-risk profile,” said study investigator Daniele Lini, MD, of ASST Spedali Civili and the University of Brescia (Italy).
“The tests are easy and cheap to be routinely performed, and they could therefore represent a valid aid to identify women that need particular monitoring and management,” he said at the 14th International Congress on Systemic Lupus Erythematosus held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.
aPL and adverse obstetric outcomes
aPL, which include lupus anticoagulant, anti–beta2-glycoprotein 1, and anticardiolipin antibodies, have been shown to induce fetal loss in animal models. Their influence on the outcome of human pregnancies, however, has been less clear, with several studies failing to prove a link between their presence and obstetric complications.
Dr. Lini and coinvestigators conducted a multicenter study involving 11 Italian centers and one Russian center, retrospectively looking for women with primary APS or women who had persistently high levels of aPL but no symptoms who had become pregnant. Of 503 pregnancies, information on complement levels before conception was available for 260, of which 184 had occurred in women with APS and 76 in women with persistently high aPL.
The pregnancies were grouped according to whether there were low (n = 93) or normal (n = 167) levels of C3 and C4 in the last 6 months.
“Women with adverse pregnancy outcomes showed significantly lower preconception complement levels than those with successful pregnancies, without any difference between APS and aPL carriers,” Dr. Lini reported.
Comparing those with low to those with high complement levels, the preterm live birth rate (before 37 weeks’ gestation) was 37% versus 18% (P < .0001).
The full-term live birth rates were a respective 42% and 72% (P < .0001).
The rate of pregnancy loss, which included both abortion and miscarriage, was a respective 21% and 10% (P = .008).
A subgroup analysis focusing on where there was triple aPL positivity found that preconception low C3 and/or C4 levels was associated with an increased rate of pregnancy loss (P = .05). This association disappeared if there was just one or two aPL present.
The researchers found no correlation between complement levels and rates of venous thromboembolism or thrombocytopenia.
Study highlights ‘impact and importance’ of complement in APS
The study indicates “the impact and the importance of complement” in APS, said Yehuda Shoenfeld, MD, the founder and head of the Zabludowicz Center for Autoimmune Diseases at the Sheba Medical Center in Tel Hashomer, Israel.
In the early days of understanding APS, said Dr. Shoenfeld, it was thought that complement was not as important as it was in systemic lupus erythematosus (SLE). The importance of raised complement seen in studies of APS would often be discounted or neglected in comparison to SLE.
However, “slowly, slowly” it has been found that “complement [in APS] is activated very similarly to SLE,” Dr. Shoenfeld noted.
“I think that it’s important to assess the component levels,” Dr. Lini said in discussion. “This is needed to be done in the preconception counseling for APS and aPL carrier patients.”
Determining whether there is single, double, or even triple aPL positivity could be useful in guiding clinical decisions.
“If we have triple positivity, that could mean that there may be a more immunologic activation of the system and that it could be useful to administrate hydroxychloroquine [to] those patients who would like to have a pregnancy,” Dr. Lini suggested.
Plus, in those with decreased complement levels, “this could be a very useful tool” to identify where something could go wrong during their pregnancy.
The study had no outside funding. Dr. Lini and Dr. Shoenfeld disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Low serum levels of two complement proteins are linked to worse pregnancy outcomes in women with antiphospholipid syndrome (APS), the results of a multicenter study appear to confirm.
The study evaluated preconception complement levels in 260 pregnancies in 197 women who had APS or carried antiphospholipid antibodies (aPL), and found that low levels of C3 and C4 in the 6 months prior to pregnancy were associated with several gestational complications and resulted in pregnancy losses.
“This study has validated, on large scale, the possible utility of preconception measurement of C3 and C4 levels to predict pregnancy loss in patients with aPL, even at a high-risk profile,” said study investigator Daniele Lini, MD, of ASST Spedali Civili and the University of Brescia (Italy).
“The tests are easy and cheap to be routinely performed, and they could therefore represent a valid aid to identify women that need particular monitoring and management,” he said at the 14th International Congress on Systemic Lupus Erythematosus held together with the 6th International Congress on Controversies in Rheumatology and Autoimmunity.
aPL and adverse obstetric outcomes
aPL, which include lupus anticoagulant, anti–beta2-glycoprotein 1, and anticardiolipin antibodies, have been shown to induce fetal loss in animal models. Their influence on the outcome of human pregnancies, however, has been less clear, with several studies failing to prove a link between their presence and obstetric complications.
Dr. Lini and coinvestigators conducted a multicenter study involving 11 Italian centers and one Russian center, retrospectively looking for women with primary APS or women who had persistently high levels of aPL but no symptoms who had become pregnant. Of 503 pregnancies, information on complement levels before conception was available for 260, of which 184 had occurred in women with APS and 76 in women with persistently high aPL.
The pregnancies were grouped according to whether there were low (n = 93) or normal (n = 167) levels of C3 and C4 in the last 6 months.
“Women with adverse pregnancy outcomes showed significantly lower preconception complement levels than those with successful pregnancies, without any difference between APS and aPL carriers,” Dr. Lini reported.
Comparing those with low to those with high complement levels, the preterm live birth rate (before 37 weeks’ gestation) was 37% versus 18% (P < .0001).
The full-term live birth rates were a respective 42% and 72% (P < .0001).
The rate of pregnancy loss, which included both abortion and miscarriage, was a respective 21% and 10% (P = .008).
A subgroup analysis focusing on where there was triple aPL positivity found that preconception low C3 and/or C4 levels was associated with an increased rate of pregnancy loss (P = .05). This association disappeared if there was just one or two aPL present.
The researchers found no correlation between complement levels and rates of venous thromboembolism or thrombocytopenia.
Study highlights ‘impact and importance’ of complement in APS
The study indicates “the impact and the importance of complement” in APS, said Yehuda Shoenfeld, MD, the founder and head of the Zabludowicz Center for Autoimmune Diseases at the Sheba Medical Center in Tel Hashomer, Israel.
In the early days of understanding APS, said Dr. Shoenfeld, it was thought that complement was not as important as it was in systemic lupus erythematosus (SLE). The importance of raised complement seen in studies of APS would often be discounted or neglected in comparison to SLE.
However, “slowly, slowly” it has been found that “complement [in APS] is activated very similarly to SLE,” Dr. Shoenfeld noted.
“I think that it’s important to assess the component levels,” Dr. Lini said in discussion. “This is needed to be done in the preconception counseling for APS and aPL carrier patients.”
Determining whether there is single, double, or even triple aPL positivity could be useful in guiding clinical decisions.
“If we have triple positivity, that could mean that there may be a more immunologic activation of the system and that it could be useful to administrate hydroxychloroquine [to] those patients who would like to have a pregnancy,” Dr. Lini suggested.
Plus, in those with decreased complement levels, “this could be a very useful tool” to identify where something could go wrong during their pregnancy.
The study had no outside funding. Dr. Lini and Dr. Shoenfeld disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FDA approves avacopan for rare ANCA autoimmune disease
U.S. regulators approved avacopan (Tavneos) for a rare immune disorder after receiving additional information to address concerns raised about the drug that were previously discussed at a public meeting in May.
ChemoCentryx, the drug’s manufacturer, today announced that the U.S. Food and Drug Administration approved the drug as an adjunctive treatment for severe active antineutrophil cytoplasmic autoantibody–associated vasculitis (also known as ANCA-associated vasculitis or ANCA vasculitis).
This systemic disease results from overactivation of the complement system, leading to inflammation and eventual destruction of small blood vessels. This can lead to organ damage and failure, with the kidney as the major target, said the company in a statement.
The avacopan approval was based in large part on the results of the ADVOCATE trial, which were highlighted in a February 2021 editorial in the New England Journal of Medicine , titled “Avacopan – Time to replace glucocorticoids?” But the FDA-approved indication for avacopan is as an adjunctive treatment of adult patients with severe active ANCA-associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]) in combination with standard therapy including glucocorticoids. “Tavneos does not eliminate glucocorticoid use,” the label states.
The ADVOCATE trial was a global, randomized, double-blind, active-controlled, double-dummy phase 3 trial of 330 patients with ANCA-associated vasculitis conducted in 20 countries, ChemoCentryx said. Participants were randomly assigned to receive either rituximab or cyclophosphamide (followed by azathioprine/mycophenolate) and either avacopan or study-supplied oral prednisone.
Subjects in both treatment groups could also receive nonprotocol glucocorticoids as needed. The study met its primary endpoints of disease remission at 26 weeks and sustained remission at 52 weeks, as assessed by the Birmingham Vasculitis Activity Score (BVAS), ChemoCentryx said. Common adverse reactions among study participants included nausea, headache, hypertension, diarrhea, vomiting, rash, fatigue, upper abdominal pain, dizziness, blood creatinine increase, and paresthesia.
In the ChemoCentryx statement, Peter A. Merkel, MD, MPH, a consultant to the company and the chief of rheumatology at the University of Pennsylvania, Philadelphia, called the avacopan clearance a “first-in-a-decade approval of a medicine for ANCA-associated vasculitis.”
“Patients will now have access to a new class of medication that provides beneficial effects for the treatment of ANCA-associated vasculitis,” Dr. Merkel said.
In reviewing the avacopan application, the FDA noted that the medicine is intended to treat “a rare and serious disease associated with high morbidity and increased mortality.”
“It is also a disease with high unmet need for new therapies,” the FDA staff said in a review of the ChemoCentryx application for approval of avacopan, which was posted online ahead of a meeting this past May.
Previous FDA concerns
In that review, FDA staff made public various concerns about the evidence used in seeking approval of the medicine. The FDA staff said there were “substantial uncertainties around the phase 3 study design and results, raising questions about the adequacy of this single trial to inform the benefit-risk assessment.”
Members of the FDA’s Arthritis Advisory Committee voted 10-8 on May 6 on a question of whether the risk-benefit profile of avacopan is adequate to support approval. The panel also voted 9-9 on whether the efficacy data support approval of avacopan, and 10-8 that the safety profile of avacopan is adequate to support approval.
ChemoCentryx in July said it filed an amendment to its new drug application (NDA) for avacopan. This appears to have answered regulators’ questions about the drug.
On a call with analysts Friday, ChemoCentryx officials outlined a marketing strategy for avacopan, with efforts focused on reaching influential rheumatologists and nephrologists. The company will set a U.S. wholesale acquisition cost for the drug of about $150,000-$200,000 a patient, in keeping with the range of prices often seen for orphan drugs. ChemoCentryx said it intends to offer financial support programs for the medicine.
ChemoCentryx said avacopan is also approved for the treatment of microscopic polyangiitis and granulomatosis with polyangiitis (the two main forms of ANCA-associated vasculitis) in Japan. The regulatory decision in Europe is expected by the end of this year.
A version of this article first appeared on Medscape.com.
U.S. regulators approved avacopan (Tavneos) for a rare immune disorder after receiving additional information to address concerns raised about the drug that were previously discussed at a public meeting in May.
ChemoCentryx, the drug’s manufacturer, today announced that the U.S. Food and Drug Administration approved the drug as an adjunctive treatment for severe active antineutrophil cytoplasmic autoantibody–associated vasculitis (also known as ANCA-associated vasculitis or ANCA vasculitis).
This systemic disease results from overactivation of the complement system, leading to inflammation and eventual destruction of small blood vessels. This can lead to organ damage and failure, with the kidney as the major target, said the company in a statement.
The avacopan approval was based in large part on the results of the ADVOCATE trial, which were highlighted in a February 2021 editorial in the New England Journal of Medicine , titled “Avacopan – Time to replace glucocorticoids?” But the FDA-approved indication for avacopan is as an adjunctive treatment of adult patients with severe active ANCA-associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]) in combination with standard therapy including glucocorticoids. “Tavneos does not eliminate glucocorticoid use,” the label states.
The ADVOCATE trial was a global, randomized, double-blind, active-controlled, double-dummy phase 3 trial of 330 patients with ANCA-associated vasculitis conducted in 20 countries, ChemoCentryx said. Participants were randomly assigned to receive either rituximab or cyclophosphamide (followed by azathioprine/mycophenolate) and either avacopan or study-supplied oral prednisone.
Subjects in both treatment groups could also receive nonprotocol glucocorticoids as needed. The study met its primary endpoints of disease remission at 26 weeks and sustained remission at 52 weeks, as assessed by the Birmingham Vasculitis Activity Score (BVAS), ChemoCentryx said. Common adverse reactions among study participants included nausea, headache, hypertension, diarrhea, vomiting, rash, fatigue, upper abdominal pain, dizziness, blood creatinine increase, and paresthesia.
In the ChemoCentryx statement, Peter A. Merkel, MD, MPH, a consultant to the company and the chief of rheumatology at the University of Pennsylvania, Philadelphia, called the avacopan clearance a “first-in-a-decade approval of a medicine for ANCA-associated vasculitis.”
“Patients will now have access to a new class of medication that provides beneficial effects for the treatment of ANCA-associated vasculitis,” Dr. Merkel said.
In reviewing the avacopan application, the FDA noted that the medicine is intended to treat “a rare and serious disease associated with high morbidity and increased mortality.”
“It is also a disease with high unmet need for new therapies,” the FDA staff said in a review of the ChemoCentryx application for approval of avacopan, which was posted online ahead of a meeting this past May.
Previous FDA concerns
In that review, FDA staff made public various concerns about the evidence used in seeking approval of the medicine. The FDA staff said there were “substantial uncertainties around the phase 3 study design and results, raising questions about the adequacy of this single trial to inform the benefit-risk assessment.”
Members of the FDA’s Arthritis Advisory Committee voted 10-8 on May 6 on a question of whether the risk-benefit profile of avacopan is adequate to support approval. The panel also voted 9-9 on whether the efficacy data support approval of avacopan, and 10-8 that the safety profile of avacopan is adequate to support approval.
ChemoCentryx in July said it filed an amendment to its new drug application (NDA) for avacopan. This appears to have answered regulators’ questions about the drug.
On a call with analysts Friday, ChemoCentryx officials outlined a marketing strategy for avacopan, with efforts focused on reaching influential rheumatologists and nephrologists. The company will set a U.S. wholesale acquisition cost for the drug of about $150,000-$200,000 a patient, in keeping with the range of prices often seen for orphan drugs. ChemoCentryx said it intends to offer financial support programs for the medicine.
ChemoCentryx said avacopan is also approved for the treatment of microscopic polyangiitis and granulomatosis with polyangiitis (the two main forms of ANCA-associated vasculitis) in Japan. The regulatory decision in Europe is expected by the end of this year.
A version of this article first appeared on Medscape.com.
U.S. regulators approved avacopan (Tavneos) for a rare immune disorder after receiving additional information to address concerns raised about the drug that were previously discussed at a public meeting in May.
ChemoCentryx, the drug’s manufacturer, today announced that the U.S. Food and Drug Administration approved the drug as an adjunctive treatment for severe active antineutrophil cytoplasmic autoantibody–associated vasculitis (also known as ANCA-associated vasculitis or ANCA vasculitis).
This systemic disease results from overactivation of the complement system, leading to inflammation and eventual destruction of small blood vessels. This can lead to organ damage and failure, with the kidney as the major target, said the company in a statement.
The avacopan approval was based in large part on the results of the ADVOCATE trial, which were highlighted in a February 2021 editorial in the New England Journal of Medicine , titled “Avacopan – Time to replace glucocorticoids?” But the FDA-approved indication for avacopan is as an adjunctive treatment of adult patients with severe active ANCA-associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]) in combination with standard therapy including glucocorticoids. “Tavneos does not eliminate glucocorticoid use,” the label states.
The ADVOCATE trial was a global, randomized, double-blind, active-controlled, double-dummy phase 3 trial of 330 patients with ANCA-associated vasculitis conducted in 20 countries, ChemoCentryx said. Participants were randomly assigned to receive either rituximab or cyclophosphamide (followed by azathioprine/mycophenolate) and either avacopan or study-supplied oral prednisone.
Subjects in both treatment groups could also receive nonprotocol glucocorticoids as needed. The study met its primary endpoints of disease remission at 26 weeks and sustained remission at 52 weeks, as assessed by the Birmingham Vasculitis Activity Score (BVAS), ChemoCentryx said. Common adverse reactions among study participants included nausea, headache, hypertension, diarrhea, vomiting, rash, fatigue, upper abdominal pain, dizziness, blood creatinine increase, and paresthesia.
In the ChemoCentryx statement, Peter A. Merkel, MD, MPH, a consultant to the company and the chief of rheumatology at the University of Pennsylvania, Philadelphia, called the avacopan clearance a “first-in-a-decade approval of a medicine for ANCA-associated vasculitis.”
“Patients will now have access to a new class of medication that provides beneficial effects for the treatment of ANCA-associated vasculitis,” Dr. Merkel said.
In reviewing the avacopan application, the FDA noted that the medicine is intended to treat “a rare and serious disease associated with high morbidity and increased mortality.”
“It is also a disease with high unmet need for new therapies,” the FDA staff said in a review of the ChemoCentryx application for approval of avacopan, which was posted online ahead of a meeting this past May.
Previous FDA concerns
In that review, FDA staff made public various concerns about the evidence used in seeking approval of the medicine. The FDA staff said there were “substantial uncertainties around the phase 3 study design and results, raising questions about the adequacy of this single trial to inform the benefit-risk assessment.”
Members of the FDA’s Arthritis Advisory Committee voted 10-8 on May 6 on a question of whether the risk-benefit profile of avacopan is adequate to support approval. The panel also voted 9-9 on whether the efficacy data support approval of avacopan, and 10-8 that the safety profile of avacopan is adequate to support approval.
ChemoCentryx in July said it filed an amendment to its new drug application (NDA) for avacopan. This appears to have answered regulators’ questions about the drug.
On a call with analysts Friday, ChemoCentryx officials outlined a marketing strategy for avacopan, with efforts focused on reaching influential rheumatologists and nephrologists. The company will set a U.S. wholesale acquisition cost for the drug of about $150,000-$200,000 a patient, in keeping with the range of prices often seen for orphan drugs. ChemoCentryx said it intends to offer financial support programs for the medicine.
ChemoCentryx said avacopan is also approved for the treatment of microscopic polyangiitis and granulomatosis with polyangiitis (the two main forms of ANCA-associated vasculitis) in Japan. The regulatory decision in Europe is expected by the end of this year.
A version of this article first appeared on Medscape.com.