Rheumatoid Arthritis

A new study in The Lancet Rheumatology examines the strength and duration of SARS-CoV-2 vaccine–induced immunoglobulin-G antibody responses over time for patients with a variety of autoimmune diseases, compared with healthy controls.

The presence of humoral antibodies to SARS-CoV-2 has been shown to correlate with protection against COVID infection. But for patients with immune-mediated inflammatory diseases (IMIDs), host response to COVID infection or to vaccination is affected by the immune dysfunction imposed by the IMID and by the use of immune-modulating drugs to treat it.

This new study finds a weaker – as shown previously – and less sustained immune response to SARS-CoV-2 vaccines in patients with a variety of IMIDs, including rheumatoid arthritis, spondyloarthritis, psoriasis, inflammatory bowel diseases, and other systemic autoimmune diseases such as lupus. It also points toward the possibility of adjusting treatment and vaccination schedules and strategies for these patients based on their antibody levels, among other factors, to preserve best protection against severe COVID.

Kmatta/Moment/Getty Images

“It is important to assess immune response in these patients to see if they still have protection against severe COVID infection,” said lead author David Simon, MD, senior clinical scientist in clinical immunology and rheumatology at University Hospital Erlangen (Germany). “We know that antibody response is an immune correlate. Therefore, it is important to see how large and durable the immune response is to the coronavirus vaccine in these IMID patients, and whether specific drugs or therapies have negative effects on their immune response.”
 

What was studied?

For this large prospective cohort study, researchers registered 5076 coronavirus-vaccinated individuals. They analyzed serum samples obtained between December 15, 2020, and December 1, 2021, from 2,535 patients diagnosed with IMIDs and participating in a prospective coronavirus study program at the Deutsches Zentrum Immuntherapie in Erlangen. The IMID patients had a mean age of 55.0 years, and 58.9% were women.

A healthy control group of 1,198 individuals without IMID who had a mean age of 40.7 years, including 53.8% men, was also recruited for the analysis. All approved coronavirus vaccines were included, following standard vaccination schedules. Antibody response was measured over time by an enzyme-linked immunosorbent assay from 8 weeks after first vaccination to week 40.

Among the findings, the healthy controls had higher postvaccine antibody levels than did those with IMIDs. But the majority of vaccinated patients with IMID were able to build up a humoral immune response to SARS-CoV-2. Patients who were taking B-cell inhibitors like rituximab (Rituxan, Genentech; and biosimilars) and T-cell inhibitors like abatacept (Orencia, Bristol Myers Squibb) for IMIDs had significantly poorer antibody response.

Greater age and the use of combination therapies for IMIDs, compared with monotherapy, further reduced immune response to the vaccine. In terms of vaccination modality, messenger RNA–based vaccines induced higher antibody levels than did vector-based vaccines. The researchers noted that patients with IMID who were given a third vaccine dose could actually catch up well with the antibody responses observed in healthy controls.

“We looked at whether different IMIDs had a different humoral response, and we also assessed if there are effects from different therapeutic strategies,” Dr. Simon explained. “It doesn’t matter so much what kind of IMID patients have; much more important is the specific drug treatment and its impact on their antibody response.” Some participants were advised to briefly stop taking some immunosuppressive treatments before or after vaccination.

One of Dr. Simon’s coauthors, statistician and rheumatologist Koray Tascilar, MD, added, “This research is important because we looked not only at who responded less, which has been previously established, but who are at greater risk of losing their immune response, and how quickly.”
 

Need to take care

“Most treatments we as rheumatologists give to our patients don’t affect their SARS-CoV-2 humoral response,” Dr. Simon said. “However, there are specific drugs that are associated with lower antibody response. With respect to those drugs, we have to be more careful.”

It is important to be able to tell patients which drugs are safe and won’t have a negative impact on their immune response to vaccinations, Dr. Tascilar said. “But it would be too strong to say we’re ready to choose therapies based on their potential impact on protection against COVID. Yes, there is a risk from catching COVID, but we need to balance that risk with the risk of not giving patients the medications that are necessary to treat their rheumatologic condition.”

These diseases are serious, sometimes life-threatening. “We might think of strategies for how to mitigate the risk of underprotection from COVID that is brought about by these treatments,” he said. For example, offering boosters sooner or more frequently, or prophylactically treating with monoclonal antibodies.

“This study, along other recent studies, has found that antibody levels in patients with immune-mediated diseases wane more rapidly than in healthy controls, and this is especially true of those on medications that interfere with the B and T cells and anticytokine therapies,” Rebecca Haberman, MD, assistant professor, division of rheumatology, New York University Langone Health, noted in an email to this news organization.

“While there is no known antibody level that specifically correlates with clinical protection, and each patient needs to be thought of individually, these findings support the use of supplemental booster dosing in patients with immune-mediated inflammatory diseases,” Dr. Haberman said, adding that her own research in this area has shown similar results.

“As a rheumatologist, I would be more likely to encourage my patients – especially those on immunomodulatory medications – to get boosted.”

Dr. Tascilar said his study does not directly answer the question of whether an earlier booster shot would be an effective strategy for patients with IMID. “In our department, we have an early boosting strategy, based on level of immune response.” But the decision of revaccination or not, and when, is based on a number of factors, not only on the level of antibodies. “It’s just part of the instruments we are using.”

The study was supported by the Deutsche Forschungsgemeinschaft. Dr. Simon and Dr. Tascilar declared no relevant financial relationships.

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

A new study in The Lancet Rheumatology examines the strength and duration of SARS-CoV-2 vaccine–induced immunoglobulin-G antibody responses over time for patients with a variety of autoimmune diseases, compared with healthy controls.

The presence of humoral antibodies to SARS-CoV-2 has been shown to correlate with protection against COVID infection. But for patients with immune-mediated inflammatory diseases (IMIDs), host response to COVID infection or to vaccination is affected by the immune dysfunction imposed by the IMID and by the use of immune-modulating drugs to treat it.

This new study finds a weaker – as shown previously – and less sustained immune response to SARS-CoV-2 vaccines in patients with a variety of IMIDs, including rheumatoid arthritis, spondyloarthritis, psoriasis, inflammatory bowel diseases, and other systemic autoimmune diseases such as lupus. It also points toward the possibility of adjusting treatment and vaccination schedules and strategies for these patients based on their antibody levels, among other factors, to preserve best protection against severe COVID.

Kmatta/Moment/Getty Images

“It is important to assess immune response in these patients to see if they still have protection against severe COVID infection,” said lead author David Simon, MD, senior clinical scientist in clinical immunology and rheumatology at University Hospital Erlangen (Germany). “We know that antibody response is an immune correlate. Therefore, it is important to see how large and durable the immune response is to the coronavirus vaccine in these IMID patients, and whether specific drugs or therapies have negative effects on their immune response.”
 

What was studied?

For this large prospective cohort study, researchers registered 5076 coronavirus-vaccinated individuals. They analyzed serum samples obtained between December 15, 2020, and December 1, 2021, from 2,535 patients diagnosed with IMIDs and participating in a prospective coronavirus study program at the Deutsches Zentrum Immuntherapie in Erlangen. The IMID patients had a mean age of 55.0 years, and 58.9% were women.

A healthy control group of 1,198 individuals without IMID who had a mean age of 40.7 years, including 53.8% men, was also recruited for the analysis. All approved coronavirus vaccines were included, following standard vaccination schedules. Antibody response was measured over time by an enzyme-linked immunosorbent assay from 8 weeks after first vaccination to week 40.

Among the findings, the healthy controls had higher postvaccine antibody levels than did those with IMIDs. But the majority of vaccinated patients with IMID were able to build up a humoral immune response to SARS-CoV-2. Patients who were taking B-cell inhibitors like rituximab (Rituxan, Genentech; and biosimilars) and T-cell inhibitors like abatacept (Orencia, Bristol Myers Squibb) for IMIDs had significantly poorer antibody response.

Greater age and the use of combination therapies for IMIDs, compared with monotherapy, further reduced immune response to the vaccine. In terms of vaccination modality, messenger RNA–based vaccines induced higher antibody levels than did vector-based vaccines. The researchers noted that patients with IMID who were given a third vaccine dose could actually catch up well with the antibody responses observed in healthy controls.

“We looked at whether different IMIDs had a different humoral response, and we also assessed if there are effects from different therapeutic strategies,” Dr. Simon explained. “It doesn’t matter so much what kind of IMID patients have; much more important is the specific drug treatment and its impact on their antibody response.” Some participants were advised to briefly stop taking some immunosuppressive treatments before or after vaccination.

One of Dr. Simon’s coauthors, statistician and rheumatologist Koray Tascilar, MD, added, “This research is important because we looked not only at who responded less, which has been previously established, but who are at greater risk of losing their immune response, and how quickly.”
 

Need to take care

“Most treatments we as rheumatologists give to our patients don’t affect their SARS-CoV-2 humoral response,” Dr. Simon said. “However, there are specific drugs that are associated with lower antibody response. With respect to those drugs, we have to be more careful.”

It is important to be able to tell patients which drugs are safe and won’t have a negative impact on their immune response to vaccinations, Dr. Tascilar said. “But it would be too strong to say we’re ready to choose therapies based on their potential impact on protection against COVID. Yes, there is a risk from catching COVID, but we need to balance that risk with the risk of not giving patients the medications that are necessary to treat their rheumatologic condition.”

These diseases are serious, sometimes life-threatening. “We might think of strategies for how to mitigate the risk of underprotection from COVID that is brought about by these treatments,” he said. For example, offering boosters sooner or more frequently, or prophylactically treating with monoclonal antibodies.

“This study, along other recent studies, has found that antibody levels in patients with immune-mediated diseases wane more rapidly than in healthy controls, and this is especially true of those on medications that interfere with the B and T cells and anticytokine therapies,” Rebecca Haberman, MD, assistant professor, division of rheumatology, New York University Langone Health, noted in an email to this news organization.

“While there is no known antibody level that specifically correlates with clinical protection, and each patient needs to be thought of individually, these findings support the use of supplemental booster dosing in patients with immune-mediated inflammatory diseases,” Dr. Haberman said, adding that her own research in this area has shown similar results.

“As a rheumatologist, I would be more likely to encourage my patients – especially those on immunomodulatory medications – to get boosted.”

Dr. Tascilar said his study does not directly answer the question of whether an earlier booster shot would be an effective strategy for patients with IMID. “In our department, we have an early boosting strategy, based on level of immune response.” But the decision of revaccination or not, and when, is based on a number of factors, not only on the level of antibodies. “It’s just part of the instruments we are using.”

The study was supported by the Deutsche Forschungsgemeinschaft. Dr. Simon and Dr. Tascilar declared no relevant financial relationships.

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

A new study in The Lancet Rheumatology examines the strength and duration of SARS-CoV-2 vaccine–induced immunoglobulin-G antibody responses over time for patients with a variety of autoimmune diseases, compared with healthy controls.

The presence of humoral antibodies to SARS-CoV-2 has been shown to correlate with protection against COVID infection. But for patients with immune-mediated inflammatory diseases (IMIDs), host response to COVID infection or to vaccination is affected by the immune dysfunction imposed by the IMID and by the use of immune-modulating drugs to treat it.

This new study finds a weaker – as shown previously – and less sustained immune response to SARS-CoV-2 vaccines in patients with a variety of IMIDs, including rheumatoid arthritis, spondyloarthritis, psoriasis, inflammatory bowel diseases, and other systemic autoimmune diseases such as lupus. It also points toward the possibility of adjusting treatment and vaccination schedules and strategies for these patients based on their antibody levels, among other factors, to preserve best protection against severe COVID.

Kmatta/Moment/Getty Images

“It is important to assess immune response in these patients to see if they still have protection against severe COVID infection,” said lead author David Simon, MD, senior clinical scientist in clinical immunology and rheumatology at University Hospital Erlangen (Germany). “We know that antibody response is an immune correlate. Therefore, it is important to see how large and durable the immune response is to the coronavirus vaccine in these IMID patients, and whether specific drugs or therapies have negative effects on their immune response.”
 

What was studied?

For this large prospective cohort study, researchers registered 5076 coronavirus-vaccinated individuals. They analyzed serum samples obtained between December 15, 2020, and December 1, 2021, from 2,535 patients diagnosed with IMIDs and participating in a prospective coronavirus study program at the Deutsches Zentrum Immuntherapie in Erlangen. The IMID patients had a mean age of 55.0 years, and 58.9% were women.

A healthy control group of 1,198 individuals without IMID who had a mean age of 40.7 years, including 53.8% men, was also recruited for the analysis. All approved coronavirus vaccines were included, following standard vaccination schedules. Antibody response was measured over time by an enzyme-linked immunosorbent assay from 8 weeks after first vaccination to week 40.

Among the findings, the healthy controls had higher postvaccine antibody levels than did those with IMIDs. But the majority of vaccinated patients with IMID were able to build up a humoral immune response to SARS-CoV-2. Patients who were taking B-cell inhibitors like rituximab (Rituxan, Genentech; and biosimilars) and T-cell inhibitors like abatacept (Orencia, Bristol Myers Squibb) for IMIDs had significantly poorer antibody response.

Greater age and the use of combination therapies for IMIDs, compared with monotherapy, further reduced immune response to the vaccine. In terms of vaccination modality, messenger RNA–based vaccines induced higher antibody levels than did vector-based vaccines. The researchers noted that patients with IMID who were given a third vaccine dose could actually catch up well with the antibody responses observed in healthy controls.

“We looked at whether different IMIDs had a different humoral response, and we also assessed if there are effects from different therapeutic strategies,” Dr. Simon explained. “It doesn’t matter so much what kind of IMID patients have; much more important is the specific drug treatment and its impact on their antibody response.” Some participants were advised to briefly stop taking some immunosuppressive treatments before or after vaccination.

One of Dr. Simon’s coauthors, statistician and rheumatologist Koray Tascilar, MD, added, “This research is important because we looked not only at who responded less, which has been previously established, but who are at greater risk of losing their immune response, and how quickly.”
 

Need to take care

“Most treatments we as rheumatologists give to our patients don’t affect their SARS-CoV-2 humoral response,” Dr. Simon said. “However, there are specific drugs that are associated with lower antibody response. With respect to those drugs, we have to be more careful.”

It is important to be able to tell patients which drugs are safe and won’t have a negative impact on their immune response to vaccinations, Dr. Tascilar said. “But it would be too strong to say we’re ready to choose therapies based on their potential impact on protection against COVID. Yes, there is a risk from catching COVID, but we need to balance that risk with the risk of not giving patients the medications that are necessary to treat their rheumatologic condition.”

These diseases are serious, sometimes life-threatening. “We might think of strategies for how to mitigate the risk of underprotection from COVID that is brought about by these treatments,” he said. For example, offering boosters sooner or more frequently, or prophylactically treating with monoclonal antibodies.

“This study, along other recent studies, has found that antibody levels in patients with immune-mediated diseases wane more rapidly than in healthy controls, and this is especially true of those on medications that interfere with the B and T cells and anticytokine therapies,” Rebecca Haberman, MD, assistant professor, division of rheumatology, New York University Langone Health, noted in an email to this news organization.

“While there is no known antibody level that specifically correlates with clinical protection, and each patient needs to be thought of individually, these findings support the use of supplemental booster dosing in patients with immune-mediated inflammatory diseases,” Dr. Haberman said, adding that her own research in this area has shown similar results.

“As a rheumatologist, I would be more likely to encourage my patients – especially those on immunomodulatory medications – to get boosted.”

Dr. Tascilar said his study does not directly answer the question of whether an earlier booster shot would be an effective strategy for patients with IMID. “In our department, we have an early boosting strategy, based on level of immune response.” But the decision of revaccination or not, and when, is based on a number of factors, not only on the level of antibodies. “It’s just part of the instruments we are using.”

The study was supported by the Deutsche Forschungsgemeinschaft. Dr. Simon and Dr. Tascilar declared no relevant financial relationships.

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

The investigational IL-6 inhibitor olokizumab fared better than placebo and was noninferior to the tumor necrosis factor inhibitor (TNFi) adalimumab (Humira) in patients with moderate to severe rheumatoid arthritis (RA) who’d had an inadequate response to methotrexate alone, according to new findings published in the New England Journal of Medicine.

The results from the phase 3, multicenter, double-blind, parallel-group, randomized, placebo- and active-comparator–controlled trial, called Clinical Rheumatoid Arthritis Development for Olokizumab (CREDO2), add to the evidence base on the drug, which was developed by R-Pharm in Russia and has been approved for use there. Last year, researchers reported results from two trials showing sustained improvements in symptoms, function, and quality of life in patients with an inadequate response to anti-TNF treatment.

“Once approved, olokizumab can be used in patients who have not responded well to either methotrexate or any biological disease-modifying antirheumatic drug or any JAK [Janus kinase] inhibitor in combination with methotrexate or alone,” said Josef Smolen, MD, chair of rheumatology at the Medical University of Vienna and the lead author on the study.

Researchers randomized 1,648 patients to 64 mg of olokizumab every 2 or 4 weeks, adalimumab every 2 weeks, or placebo. All patient groups continued to receive methotrexate. A total of 89.7% of the participants completed 24 weeks of treatment. By that point, 74.1% of those receiving olokizumab every 2 weeks had achieved an ACR 20 response, an improvement of at least 20% in American College of Rheumatology response criteria, including tender and swollen joints, and 71.4% in the group receiving olokizumab every 4 weeks; 69.0% in the adalimumab group; and 46.5% in the placebo group had achieved an ACR 20 response. Olokizumab benefits were also seen for Disease Activity Score in 28 joints, disability index scores, and ACR 50 responses, the researchers reported.

Approved IL-6 inhibitors tocilizumab (Actemra) and sarilumab (Kevzara) target the interleukin (IL)-6 receptor (IL-6R), but olokizumab targets a protein, glycoprotein 130 (GP130), to which the IL-6 and IL-6–receptor complex binds. This approach could offer an added benefit, Dr. Smolen said.

“Previously studied anti–IL-6 antibodies and anti–IL-6R antibodies prevent binding of IL-6 to the IL-6R,” he said. “Moreover, the amount of protein needed to inhibit IL-6 is lower compared to the approved antireceptor antibodies. Olokizumab has also been shown to be effective when given every 4 weeks in many patients, compared with the need for weekly or every-other-week applications with tocilizumab and sarilumab. From these perspectives, this novel mode of action may, indeed, provide an advantage.”

ACR 70 – an improvement of at least 70% in the ACR response criteria – was an exploratory endpoint in the trial. This response was seen in 28% of those receiving olokizumab, compared with 11% in the placebo group, but researchers cautioned that “no conclusions can be drawn from these results.”

Another drug, sirukumab, also targeted the IL-6 ligand rather than the receptor, but was rejected by regulators in 2017 because so many more deaths occurred in the treatment group than the placebo group.

Dr. Smolen noted that there are three binding sites for IL-6, but olokizumab is the first to target site 3, the binding site for GP130. Mortality concerns haven’t been seen for olokizumab. There were three serious adverse events leading to death in the olokizumab every-2-weeks group; two in the olokizumab every-4-weeks group; one in the adalimumab group; and one in the placebo group.

“The fact that olokizumab targets another site on the IL-6 molecule than sirukumab may be a reason for the difference,” Dr. Smolen said.

Still, researchers noted that the time horizon for this trial is not very long.

“The trial was conducted in a relatively small number of patients and over a short duration, especially for the assessment of rare events or events requiring longer durations of exposure,” they wrote. “Longer and larger trials are required to determine the efficacy and safety of olokizumab in patients with rheumatoid arthritis.”

Dr. Smolen said he expects R-Pharm will file for regulatory approval in the United States and Europe, outside of Russia, in the next year.

Paul Emery, MD, professor of rheumatology at the University of Leeds (England) who has researched IL-6 therapy in RA, said olokizumab appears to be an effective product, but its use remains a question.

“The question is where it will fit into treatment strategies,” he said. “It’ll be very interesting.”

Dr. Emery pointed out that tocilizumab, which inhibits IL-6 by blocking the IL-6 receptor, was approved in the United States at a dosage that wasn’t optimally effective after failure with TNF inhibitors (TNFi), and wondered whether olokizumab would fare differently in this regard.

While Dr. Emery said it was important that no bad safety signal has been seen, he noted that “it’s a short-term study, and you do need to see the long-term data.”

“It seems to work at both the intervals it was tested at, 2 and 4 weeks. The unknowns are whether it will be as effective as IL-6 receptor blockers in other diseases,” such as giant cell arteritis, “and early disease, and whether it will work as well post TNFi,” he said. “It could be used as first advanced therapy for people with contraindications to TNFi, but initially the majority of its use will be after TNFi, and that’s why you need to see more data on such patients.”

He added: “The final issue will be pricing. Therefore, a positive study – but much is still unknown.”

The study was supported by R-Pharm. Dr. Smolen reports financial relationships with R-Pharm, AbbVie, Janssen, Eli Lilly, Gilead, Pfizer, and other companies. Dr. Emery reports financial relationships with AbbVie, AstraZeneca, Janssen, Pfizer, Roche, and other companies, but not olokizumab manufacturer R-Pharm.

The investigational IL-6 inhibitor olokizumab fared better than placebo and was noninferior to the tumor necrosis factor inhibitor (TNFi) adalimumab (Humira) in patients with moderate to severe rheumatoid arthritis (RA) who’d had an inadequate response to methotrexate alone, according to new findings published in the New England Journal of Medicine.

The results from the phase 3, multicenter, double-blind, parallel-group, randomized, placebo- and active-comparator–controlled trial, called Clinical Rheumatoid Arthritis Development for Olokizumab (CREDO2), add to the evidence base on the drug, which was developed by R-Pharm in Russia and has been approved for use there. Last year, researchers reported results from two trials showing sustained improvements in symptoms, function, and quality of life in patients with an inadequate response to anti-TNF treatment.

“Once approved, olokizumab can be used in patients who have not responded well to either methotrexate or any biological disease-modifying antirheumatic drug or any JAK [Janus kinase] inhibitor in combination with methotrexate or alone,” said Josef Smolen, MD, chair of rheumatology at the Medical University of Vienna and the lead author on the study.

Researchers randomized 1,648 patients to 64 mg of olokizumab every 2 or 4 weeks, adalimumab every 2 weeks, or placebo. All patient groups continued to receive methotrexate. A total of 89.7% of the participants completed 24 weeks of treatment. By that point, 74.1% of those receiving olokizumab every 2 weeks had achieved an ACR 20 response, an improvement of at least 20% in American College of Rheumatology response criteria, including tender and swollen joints, and 71.4% in the group receiving olokizumab every 4 weeks; 69.0% in the adalimumab group; and 46.5% in the placebo group had achieved an ACR 20 response. Olokizumab benefits were also seen for Disease Activity Score in 28 joints, disability index scores, and ACR 50 responses, the researchers reported.

Approved IL-6 inhibitors tocilizumab (Actemra) and sarilumab (Kevzara) target the interleukin (IL)-6 receptor (IL-6R), but olokizumab targets a protein, glycoprotein 130 (GP130), to which the IL-6 and IL-6–receptor complex binds. This approach could offer an added benefit, Dr. Smolen said.

“Previously studied anti–IL-6 antibodies and anti–IL-6R antibodies prevent binding of IL-6 to the IL-6R,” he said. “Moreover, the amount of protein needed to inhibit IL-6 is lower compared to the approved antireceptor antibodies. Olokizumab has also been shown to be effective when given every 4 weeks in many patients, compared with the need for weekly or every-other-week applications with tocilizumab and sarilumab. From these perspectives, this novel mode of action may, indeed, provide an advantage.”

ACR 70 – an improvement of at least 70% in the ACR response criteria – was an exploratory endpoint in the trial. This response was seen in 28% of those receiving olokizumab, compared with 11% in the placebo group, but researchers cautioned that “no conclusions can be drawn from these results.”

Another drug, sirukumab, also targeted the IL-6 ligand rather than the receptor, but was rejected by regulators in 2017 because so many more deaths occurred in the treatment group than the placebo group.

Dr. Smolen noted that there are three binding sites for IL-6, but olokizumab is the first to target site 3, the binding site for GP130. Mortality concerns haven’t been seen for olokizumab. There were three serious adverse events leading to death in the olokizumab every-2-weeks group; two in the olokizumab every-4-weeks group; one in the adalimumab group; and one in the placebo group.

“The fact that olokizumab targets another site on the IL-6 molecule than sirukumab may be a reason for the difference,” Dr. Smolen said.

Still, researchers noted that the time horizon for this trial is not very long.

“The trial was conducted in a relatively small number of patients and over a short duration, especially for the assessment of rare events or events requiring longer durations of exposure,” they wrote. “Longer and larger trials are required to determine the efficacy and safety of olokizumab in patients with rheumatoid arthritis.”

Dr. Smolen said he expects R-Pharm will file for regulatory approval in the United States and Europe, outside of Russia, in the next year.

Paul Emery, MD, professor of rheumatology at the University of Leeds (England) who has researched IL-6 therapy in RA, said olokizumab appears to be an effective product, but its use remains a question.

“The question is where it will fit into treatment strategies,” he said. “It’ll be very interesting.”

Dr. Emery pointed out that tocilizumab, which inhibits IL-6 by blocking the IL-6 receptor, was approved in the United States at a dosage that wasn’t optimally effective after failure with TNF inhibitors (TNFi), and wondered whether olokizumab would fare differently in this regard.

While Dr. Emery said it was important that no bad safety signal has been seen, he noted that “it’s a short-term study, and you do need to see the long-term data.”

“It seems to work at both the intervals it was tested at, 2 and 4 weeks. The unknowns are whether it will be as effective as IL-6 receptor blockers in other diseases,” such as giant cell arteritis, “and early disease, and whether it will work as well post TNFi,” he said. “It could be used as first advanced therapy for people with contraindications to TNFi, but initially the majority of its use will be after TNFi, and that’s why you need to see more data on such patients.”

He added: “The final issue will be pricing. Therefore, a positive study – but much is still unknown.”

The study was supported by R-Pharm. Dr. Smolen reports financial relationships with R-Pharm, AbbVie, Janssen, Eli Lilly, Gilead, Pfizer, and other companies. Dr. Emery reports financial relationships with AbbVie, AstraZeneca, Janssen, Pfizer, Roche, and other companies, but not olokizumab manufacturer R-Pharm.

The investigational IL-6 inhibitor olokizumab fared better than placebo and was noninferior to the tumor necrosis factor inhibitor (TNFi) adalimumab (Humira) in patients with moderate to severe rheumatoid arthritis (RA) who’d had an inadequate response to methotrexate alone, according to new findings published in the New England Journal of Medicine.

The results from the phase 3, multicenter, double-blind, parallel-group, randomized, placebo- and active-comparator–controlled trial, called Clinical Rheumatoid Arthritis Development for Olokizumab (CREDO2), add to the evidence base on the drug, which was developed by R-Pharm in Russia and has been approved for use there. Last year, researchers reported results from two trials showing sustained improvements in symptoms, function, and quality of life in patients with an inadequate response to anti-TNF treatment.

“Once approved, olokizumab can be used in patients who have not responded well to either methotrexate or any biological disease-modifying antirheumatic drug or any JAK [Janus kinase] inhibitor in combination with methotrexate or alone,” said Josef Smolen, MD, chair of rheumatology at the Medical University of Vienna and the lead author on the study.

Researchers randomized 1,648 patients to 64 mg of olokizumab every 2 or 4 weeks, adalimumab every 2 weeks, or placebo. All patient groups continued to receive methotrexate. A total of 89.7% of the participants completed 24 weeks of treatment. By that point, 74.1% of those receiving olokizumab every 2 weeks had achieved an ACR 20 response, an improvement of at least 20% in American College of Rheumatology response criteria, including tender and swollen joints, and 71.4% in the group receiving olokizumab every 4 weeks; 69.0% in the adalimumab group; and 46.5% in the placebo group had achieved an ACR 20 response. Olokizumab benefits were also seen for Disease Activity Score in 28 joints, disability index scores, and ACR 50 responses, the researchers reported.

Approved IL-6 inhibitors tocilizumab (Actemra) and sarilumab (Kevzara) target the interleukin (IL)-6 receptor (IL-6R), but olokizumab targets a protein, glycoprotein 130 (GP130), to which the IL-6 and IL-6–receptor complex binds. This approach could offer an added benefit, Dr. Smolen said.

“Previously studied anti–IL-6 antibodies and anti–IL-6R antibodies prevent binding of IL-6 to the IL-6R,” he said. “Moreover, the amount of protein needed to inhibit IL-6 is lower compared to the approved antireceptor antibodies. Olokizumab has also been shown to be effective when given every 4 weeks in many patients, compared with the need for weekly or every-other-week applications with tocilizumab and sarilumab. From these perspectives, this novel mode of action may, indeed, provide an advantage.”

ACR 70 – an improvement of at least 70% in the ACR response criteria – was an exploratory endpoint in the trial. This response was seen in 28% of those receiving olokizumab, compared with 11% in the placebo group, but researchers cautioned that “no conclusions can be drawn from these results.”

Another drug, sirukumab, also targeted the IL-6 ligand rather than the receptor, but was rejected by regulators in 2017 because so many more deaths occurred in the treatment group than the placebo group.

Dr. Smolen noted that there are three binding sites for IL-6, but olokizumab is the first to target site 3, the binding site for GP130. Mortality concerns haven’t been seen for olokizumab. There were three serious adverse events leading to death in the olokizumab every-2-weeks group; two in the olokizumab every-4-weeks group; one in the adalimumab group; and one in the placebo group.

“The fact that olokizumab targets another site on the IL-6 molecule than sirukumab may be a reason for the difference,” Dr. Smolen said.

Still, researchers noted that the time horizon for this trial is not very long.

“The trial was conducted in a relatively small number of patients and over a short duration, especially for the assessment of rare events or events requiring longer durations of exposure,” they wrote. “Longer and larger trials are required to determine the efficacy and safety of olokizumab in patients with rheumatoid arthritis.”

Dr. Smolen said he expects R-Pharm will file for regulatory approval in the United States and Europe, outside of Russia, in the next year.

Paul Emery, MD, professor of rheumatology at the University of Leeds (England) who has researched IL-6 therapy in RA, said olokizumab appears to be an effective product, but its use remains a question.

“The question is where it will fit into treatment strategies,” he said. “It’ll be very interesting.”

Dr. Emery pointed out that tocilizumab, which inhibits IL-6 by blocking the IL-6 receptor, was approved in the United States at a dosage that wasn’t optimally effective after failure with TNF inhibitors (TNFi), and wondered whether olokizumab would fare differently in this regard.

While Dr. Emery said it was important that no bad safety signal has been seen, he noted that “it’s a short-term study, and you do need to see the long-term data.”

“It seems to work at both the intervals it was tested at, 2 and 4 weeks. The unknowns are whether it will be as effective as IL-6 receptor blockers in other diseases,” such as giant cell arteritis, “and early disease, and whether it will work as well post TNFi,” he said. “It could be used as first advanced therapy for people with contraindications to TNFi, but initially the majority of its use will be after TNFi, and that’s why you need to see more data on such patients.”

He added: “The final issue will be pricing. Therefore, a positive study – but much is still unknown.”

The study was supported by R-Pharm. Dr. Smolen reports financial relationships with R-Pharm, AbbVie, Janssen, Eli Lilly, Gilead, Pfizer, and other companies. Dr. Emery reports financial relationships with AbbVie, AstraZeneca, Janssen, Pfizer, Roche, and other companies, but not olokizumab manufacturer R-Pharm.

Key clinical point: Patients with rheumatoid arthritis (RA) and low or moderate disease activity were at a higher risk for hospitalized infections compared with those in remission.

Major finding: Compared with patients attaining remission, patients attaining low disease activity (adjusted hazard ratio [aHR] 1.60; 95% CI 1.13-2.27) and moderate disease activity (aHR 1.83; 95% CI 1.29-2.61) were at a higher risk for hospitalized infections.

Study details: Findings are from a prospective observational cohort study including 3254 patients with moderate RA from the CorEvitas RA registry.

Disclosures: H Yun and JR Curtis declared receiving support from US National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. Two authors reported being employees and shareholders of CorEvitas LLC. Several authors reported receiving research funding from or serving on speakers bureaus or as consultants for various sources.

Source: Yun H et al. Rheumatoid arthritis disease activity and hospitalized infection in a large U.S. registry. Arthritis Care Res (Hoboken). 2022 (Jul 22). Doi: 10.1002/acr.24984

Key clinical point: Patients with rheumatoid arthritis (RA) and low or moderate disease activity were at a higher risk for hospitalized infections compared with those in remission.

Major finding: Compared with patients attaining remission, patients attaining low disease activity (adjusted hazard ratio [aHR] 1.60; 95% CI 1.13-2.27) and moderate disease activity (aHR 1.83; 95% CI 1.29-2.61) were at a higher risk for hospitalized infections.

Study details: Findings are from a prospective observational cohort study including 3254 patients with moderate RA from the CorEvitas RA registry.

Disclosures: H Yun and JR Curtis declared receiving support from US National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. Two authors reported being employees and shareholders of CorEvitas LLC. Several authors reported receiving research funding from or serving on speakers bureaus or as consultants for various sources.

Source: Yun H et al. Rheumatoid arthritis disease activity and hospitalized infection in a large U.S. registry. Arthritis Care Res (Hoboken). 2022 (Jul 22). Doi: 10.1002/acr.24984

Key clinical point: Patients with rheumatoid arthritis (RA) and low or moderate disease activity were at a higher risk for hospitalized infections compared with those in remission.

Major finding: Compared with patients attaining remission, patients attaining low disease activity (adjusted hazard ratio [aHR] 1.60; 95% CI 1.13-2.27) and moderate disease activity (aHR 1.83; 95% CI 1.29-2.61) were at a higher risk for hospitalized infections.

Study details: Findings are from a prospective observational cohort study including 3254 patients with moderate RA from the CorEvitas RA registry.

Disclosures: H Yun and JR Curtis declared receiving support from US National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. Two authors reported being employees and shareholders of CorEvitas LLC. Several authors reported receiving research funding from or serving on speakers bureaus or as consultants for various sources.

Source: Yun H et al. Rheumatoid arthritis disease activity and hospitalized infection in a large U.S. registry. Arthritis Care Res (Hoboken). 2022 (Jul 22). Doi: 10.1002/acr.24984

Key clinical point: The rate of development of rheumatoid arthritis (RA) was lower in patients with diabetes who used vs did not use sulfonylureas or biguanides, with biguanides appearing to have a more rapid and sulfonylureas having a longer effect in lowering RA incidence.

Major finding: Among patients with diabetes, sulfonylureas or biguanides users vs nonusers were at a reduced risk of developing RA (adjusted hazard ratio 0.73; 95% CI 0.60-0.90), with the risk being lower in those prescribed biguanides for >180 days within 1 year (adjusted odds ratio [aOR] 0.72; 95% CI 0.53-0.99) and those prescribed sulfonylureas for >365 days within 3 years (aOR 0.62; 95% CI 0.46-0.84) of the first RA visit.

Study details: Findings are from a cohort study including 94,141 patients with diabetes, of which 494 patients developed RA and were age- and sex-matched with 988 patients who did not develop RA.

Disclosures: This study was supported by Chung Shan Medical University Hospital, Taiwan, Chang Gung Memorial Hospital, and others. The authors declared no conflicts of interest.

Source: Su YJ et al. Sulfonylureas or biguanides is associated with a lower risk of rheumatoid arthritis in patients with diabetes: A nationwide cohort study. Front Med (Lausanne). 2022;9:934184 (Jul 27). Doi: 10.3389/fmed.2022.934184

Key clinical point: The rate of development of rheumatoid arthritis (RA) was lower in patients with diabetes who used vs did not use sulfonylureas or biguanides, with biguanides appearing to have a more rapid and sulfonylureas having a longer effect in lowering RA incidence.

Major finding: Among patients with diabetes, sulfonylureas or biguanides users vs nonusers were at a reduced risk of developing RA (adjusted hazard ratio 0.73; 95% CI 0.60-0.90), with the risk being lower in those prescribed biguanides for >180 days within 1 year (adjusted odds ratio [aOR] 0.72; 95% CI 0.53-0.99) and those prescribed sulfonylureas for >365 days within 3 years (aOR 0.62; 95% CI 0.46-0.84) of the first RA visit.

Study details: Findings are from a cohort study including 94,141 patients with diabetes, of which 494 patients developed RA and were age- and sex-matched with 988 patients who did not develop RA.

Disclosures: This study was supported by Chung Shan Medical University Hospital, Taiwan, Chang Gung Memorial Hospital, and others. The authors declared no conflicts of interest.

Source: Su YJ et al. Sulfonylureas or biguanides is associated with a lower risk of rheumatoid arthritis in patients with diabetes: A nationwide cohort study. Front Med (Lausanne). 2022;9:934184 (Jul 27). Doi: 10.3389/fmed.2022.934184

Key clinical point: The rate of development of rheumatoid arthritis (RA) was lower in patients with diabetes who used vs did not use sulfonylureas or biguanides, with biguanides appearing to have a more rapid and sulfonylureas having a longer effect in lowering RA incidence.

Major finding: Among patients with diabetes, sulfonylureas or biguanides users vs nonusers were at a reduced risk of developing RA (adjusted hazard ratio 0.73; 95% CI 0.60-0.90), with the risk being lower in those prescribed biguanides for >180 days within 1 year (adjusted odds ratio [aOR] 0.72; 95% CI 0.53-0.99) and those prescribed sulfonylureas for >365 days within 3 years (aOR 0.62; 95% CI 0.46-0.84) of the first RA visit.

Study details: Findings are from a cohort study including 94,141 patients with diabetes, of which 494 patients developed RA and were age- and sex-matched with 988 patients who did not develop RA.

Disclosures: This study was supported by Chung Shan Medical University Hospital, Taiwan, Chang Gung Memorial Hospital, and others. The authors declared no conflicts of interest.

Source: Su YJ et al. Sulfonylureas or biguanides is associated with a lower risk of rheumatoid arthritis in patients with diabetes: A nationwide cohort study. Front Med (Lausanne). 2022;9:934184 (Jul 27). Doi: 10.3389/fmed.2022.934184

Key clinical point: A serum lipid profile rich in long chain n-3 and n-6 polyunsaturated fatty acids (PUFA) was independently associated with a lower 6-month disease activity in a cohort of patients with early rheumatoid arthritis (RA).

Major finding: At 6 months, the odds of having a 28-joint Disease Activity Score of ≥5.1 was significantly lower in patients in higher tertiles of n-3 PUFA (odds ratio for tertile 3 vs 1 [ORt] 0.49; 95% CI 0.25-0.97) and n-6 PUFA (ORt 0.51; 95% CI 0.28-0.95), with the association being independent of baseline C-reactive protein levels.

Study details: This was a longitudinal cohort study including 669 patients with early RA.

Disclosures: This study was supported by Sorbonne Paris Nord University. The authors declared no conflicts of interest.

Source: Sigaux J et al. Serum fatty acid profiles are associated with disease activity in early rheumatoid arthritis: Results from the ESPOIR cohort. Nutrients. 2022;14(14):2947 (Jul 19). Doi:  10.3390/nu14142947

Key clinical point: A serum lipid profile rich in long chain n-3 and n-6 polyunsaturated fatty acids (PUFA) was independently associated with a lower 6-month disease activity in a cohort of patients with early rheumatoid arthritis (RA).

Major finding: At 6 months, the odds of having a 28-joint Disease Activity Score of ≥5.1 was significantly lower in patients in higher tertiles of n-3 PUFA (odds ratio for tertile 3 vs 1 [ORt] 0.49; 95% CI 0.25-0.97) and n-6 PUFA (ORt 0.51; 95% CI 0.28-0.95), with the association being independent of baseline C-reactive protein levels.

Study details: This was a longitudinal cohort study including 669 patients with early RA.

Disclosures: This study was supported by Sorbonne Paris Nord University. The authors declared no conflicts of interest.

Source: Sigaux J et al. Serum fatty acid profiles are associated with disease activity in early rheumatoid arthritis: Results from the ESPOIR cohort. Nutrients. 2022;14(14):2947 (Jul 19). Doi:  10.3390/nu14142947

Key clinical point: A serum lipid profile rich in long chain n-3 and n-6 polyunsaturated fatty acids (PUFA) was independently associated with a lower 6-month disease activity in a cohort of patients with early rheumatoid arthritis (RA).

Major finding: At 6 months, the odds of having a 28-joint Disease Activity Score of ≥5.1 was significantly lower in patients in higher tertiles of n-3 PUFA (odds ratio for tertile 3 vs 1 [ORt] 0.49; 95% CI 0.25-0.97) and n-6 PUFA (ORt 0.51; 95% CI 0.28-0.95), with the association being independent of baseline C-reactive protein levels.

Study details: This was a longitudinal cohort study including 669 patients with early RA.

Disclosures: This study was supported by Sorbonne Paris Nord University. The authors declared no conflicts of interest.

Source: Sigaux J et al. Serum fatty acid profiles are associated with disease activity in early rheumatoid arthritis: Results from the ESPOIR cohort. Nutrients. 2022;14(14):2947 (Jul 19). Doi:  10.3390/nu14142947

Key clinical point: Patients with rheumatoid arthritis (RA) who were positive for anti-Sjögren's-syndrome-related antigen A (SSA) antibody were less responsive to initial methotrexate treatment compared with patients negative for anti-SSA antibody.

Major finding: At 6 months, a significantly lower proportion of patients in the anti-SSA antibody positive vs negative group achieved low disease activity based on the 28-joint Disease Activity Score-C-reactive protein (56.2% vs 75.8%; P  =  .03). Patients positive for anti-SSA antibody had a higher patient visual analogue score (median score 22 vs 19; P  =  .038) and use of nonsteroidal anti-inflammatory drugs (37.5% vs 18.0%; P  =  .018).

Study details: This was a retrospective cohort study including 210 methotrexate- or biologic disease-modifying antirheumatic drug-naive patients with RA who initiated methotrexate, of which 32 patients tested positive for anti-SSA antibody.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Waki D et al. Effects of anti-SSA antibodies on the response to methotrexate in rheumatoid arthritis: A retrospective multicenter observational study. PLoS One. 2022;17(7):e0271921 (Jul 22). Doi: 10.1371/journal.pone.0271921

Key clinical point: Patients with rheumatoid arthritis (RA) who were positive for anti-Sjögren's-syndrome-related antigen A (SSA) antibody were less responsive to initial methotrexate treatment compared with patients negative for anti-SSA antibody.

Major finding: At 6 months, a significantly lower proportion of patients in the anti-SSA antibody positive vs negative group achieved low disease activity based on the 28-joint Disease Activity Score-C-reactive protein (56.2% vs 75.8%; P  =  .03). Patients positive for anti-SSA antibody had a higher patient visual analogue score (median score 22 vs 19; P  =  .038) and use of nonsteroidal anti-inflammatory drugs (37.5% vs 18.0%; P  =  .018).

Study details: This was a retrospective cohort study including 210 methotrexate- or biologic disease-modifying antirheumatic drug-naive patients with RA who initiated methotrexate, of which 32 patients tested positive for anti-SSA antibody.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Waki D et al. Effects of anti-SSA antibodies on the response to methotrexate in rheumatoid arthritis: A retrospective multicenter observational study. PLoS One. 2022;17(7):e0271921 (Jul 22). Doi: 10.1371/journal.pone.0271921

Key clinical point: Patients with rheumatoid arthritis (RA) who were positive for anti-Sjögren's-syndrome-related antigen A (SSA) antibody were less responsive to initial methotrexate treatment compared with patients negative for anti-SSA antibody.

Major finding: At 6 months, a significantly lower proportion of patients in the anti-SSA antibody positive vs negative group achieved low disease activity based on the 28-joint Disease Activity Score-C-reactive protein (56.2% vs 75.8%; P  =  .03). Patients positive for anti-SSA antibody had a higher patient visual analogue score (median score 22 vs 19; P  =  .038) and use of nonsteroidal anti-inflammatory drugs (37.5% vs 18.0%; P  =  .018).

Study details: This was a retrospective cohort study including 210 methotrexate- or biologic disease-modifying antirheumatic drug-naive patients with RA who initiated methotrexate, of which 32 patients tested positive for anti-SSA antibody.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Waki D et al. Effects of anti-SSA antibodies on the response to methotrexate in rheumatoid arthritis: A retrospective multicenter observational study. PLoS One. 2022;17(7):e0271921 (Jul 22). Doi: 10.1371/journal.pone.0271921

Key clinical point: Patients with rheumatoid arthritis (RA) who had symptoms of clinically active RA and cardiovascular disease were at an increased risk for dementia.

Major finding: Apart from the universally recognized risk factors for dementia, such as older age at RA incidence, hypertension, depression, and anxiety, RA disease characteristics, such as the presence of rheumatoid nodules (adjusted hazard ratio [aHR] 1.76; 95% CI 1.05-2.95), large joint swellings (aHR 2.11; 95% CI 1.33-3.34), and any cardiovascular disease at anytime after RA incidence (aHR 2.25; 95% CI 1.38-3.66) were significantly associated with an increased risk for dementia.

Study details: This was a retrospective cohort study including 886 patients with incident RA and without prior dementia, of which 103 patients developed dementia during a median follow-up of 8.5 years.

Disclosures: This study was supported by the US National Institutes of Health, National Institute of Aging, and National Institute of Arthritis and Musculoskeletal and Skin Diseases. M Vassilaki reported receiving research funding and owning equity in various companies. MM Mielke reported receiving research grants or funding from and serving as a consultant for various sources.

Source: Kodishala C et al. Risk factors for dementia in patients with incident rheumatoid arthritis: A population-based cohort study. J Rheumatol. 2022 (Jul 15). Doi: 10.3899/jrheum.220200

Key clinical point: Patients with rheumatoid arthritis (RA) who had symptoms of clinically active RA and cardiovascular disease were at an increased risk for dementia.

Major finding: Apart from the universally recognized risk factors for dementia, such as older age at RA incidence, hypertension, depression, and anxiety, RA disease characteristics, such as the presence of rheumatoid nodules (adjusted hazard ratio [aHR] 1.76; 95% CI 1.05-2.95), large joint swellings (aHR 2.11; 95% CI 1.33-3.34), and any cardiovascular disease at anytime after RA incidence (aHR 2.25; 95% CI 1.38-3.66) were significantly associated with an increased risk for dementia.

Study details: This was a retrospective cohort study including 886 patients with incident RA and without prior dementia, of which 103 patients developed dementia during a median follow-up of 8.5 years.

Disclosures: This study was supported by the US National Institutes of Health, National Institute of Aging, and National Institute of Arthritis and Musculoskeletal and Skin Diseases. M Vassilaki reported receiving research funding and owning equity in various companies. MM Mielke reported receiving research grants or funding from and serving as a consultant for various sources.

Source: Kodishala C et al. Risk factors for dementia in patients with incident rheumatoid arthritis: A population-based cohort study. J Rheumatol. 2022 (Jul 15). Doi: 10.3899/jrheum.220200

Key clinical point: Patients with rheumatoid arthritis (RA) who had symptoms of clinically active RA and cardiovascular disease were at an increased risk for dementia.

Major finding: Apart from the universally recognized risk factors for dementia, such as older age at RA incidence, hypertension, depression, and anxiety, RA disease characteristics, such as the presence of rheumatoid nodules (adjusted hazard ratio [aHR] 1.76; 95% CI 1.05-2.95), large joint swellings (aHR 2.11; 95% CI 1.33-3.34), and any cardiovascular disease at anytime after RA incidence (aHR 2.25; 95% CI 1.38-3.66) were significantly associated with an increased risk for dementia.

Study details: This was a retrospective cohort study including 886 patients with incident RA and without prior dementia, of which 103 patients developed dementia during a median follow-up of 8.5 years.

Disclosures: This study was supported by the US National Institutes of Health, National Institute of Aging, and National Institute of Arthritis and Musculoskeletal and Skin Diseases. M Vassilaki reported receiving research funding and owning equity in various companies. MM Mielke reported receiving research grants or funding from and serving as a consultant for various sources.

Source: Kodishala C et al. Risk factors for dementia in patients with incident rheumatoid arthritis: A population-based cohort study. J Rheumatol. 2022 (Jul 15). Doi: 10.3899/jrheum.220200

Key clinical point: Janus kinase inhibitors (JAKi) ameliorated the signs and symptoms of rheumatoid arthritis (RA) and improved the health-related quality of life more effectively than placebo; however, safety concerns should be addressed.

Major finding: JAKi vs placebo significantly improved the American College of Rheumatology ≥20% improvement response rate (risk ratio [RR] 2.03; P < .001) and Health Assessment Questionnaire-Disability Index (mean difference −0.31; P < .001), but were associated with a higher risk for ≥1 adverse events (RR 1.10; P < .001) and infections (RR 1.29; P < .001).

Study details: Findings are from a systematic review and meta-analysis of pooled data from 37 randomized controlled trials that evaluated JAKi for RA and included a total of 15,174 participants.

Disclosures: This study was supported by the National Natural Science Foundation of China, West China Hospital, and others. The authors declared no conflicts of interest.

Source: Wang F et al. Efficacy and safety of JAK inhibitors for rheumatoid arthritis: A meta-analysis. J Clin Med. 2022;11(15):4459 (Jul 30). Doi: 10.3390/jcm11154459

Key clinical point: Janus kinase inhibitors (JAKi) ameliorated the signs and symptoms of rheumatoid arthritis (RA) and improved the health-related quality of life more effectively than placebo; however, safety concerns should be addressed.

Major finding: JAKi vs placebo significantly improved the American College of Rheumatology ≥20% improvement response rate (risk ratio [RR] 2.03; P < .001) and Health Assessment Questionnaire-Disability Index (mean difference −0.31; P < .001), but were associated with a higher risk for ≥1 adverse events (RR 1.10; P < .001) and infections (RR 1.29; P < .001).

Study details: Findings are from a systematic review and meta-analysis of pooled data from 37 randomized controlled trials that evaluated JAKi for RA and included a total of 15,174 participants.

Disclosures: This study was supported by the National Natural Science Foundation of China, West China Hospital, and others. The authors declared no conflicts of interest.

Source: Wang F et al. Efficacy and safety of JAK inhibitors for rheumatoid arthritis: A meta-analysis. J Clin Med. 2022;11(15):4459 (Jul 30). Doi: 10.3390/jcm11154459

Key clinical point: Janus kinase inhibitors (JAKi) ameliorated the signs and symptoms of rheumatoid arthritis (RA) and improved the health-related quality of life more effectively than placebo; however, safety concerns should be addressed.

Major finding: JAKi vs placebo significantly improved the American College of Rheumatology ≥20% improvement response rate (risk ratio [RR] 2.03; P < .001) and Health Assessment Questionnaire-Disability Index (mean difference −0.31; P < .001), but were associated with a higher risk for ≥1 adverse events (RR 1.10; P < .001) and infections (RR 1.29; P < .001).

Study details: Findings are from a systematic review and meta-analysis of pooled data from 37 randomized controlled trials that evaluated JAKi for RA and included a total of 15,174 participants.

Disclosures: This study was supported by the National Natural Science Foundation of China, West China Hospital, and others. The authors declared no conflicts of interest.

Source: Wang F et al. Efficacy and safety of JAK inhibitors for rheumatoid arthritis: A meta-analysis. J Clin Med. 2022;11(15):4459 (Jul 30). Doi: 10.3390/jcm11154459

Key clinical point: Discontinuation of biologic disease-modifying antirheumatic drugs (bDMARD) upon testing positive for pregnancy is associated with and a major risk factor for disease flare during pregnancy in a large proportion of women with rheumatoid arthritis (RA) and good disease control prior to conception.

Major finding: Overall, flare was reported by 37% of patients during pregnancy and was associated with discontinuing bDMARD upon testing positive for pregnancy (odds ratio [OR] 2.857; P  =  .034) and previous use of >1 bDMARD (OR 4.1; P  =  .019). Patients with vs without disease flare during pregnancy were more likely to report preterm delivery (27% vs 7%; OR 4.625; P  =  .034).

Study details: This study analyzed the retrospectively collected data of 73 pregnancies in 63 women with RA and good disease control during conception who were prospectively followed through their pregnancies.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Gerardi MC et al. Stopping bDMARDs at the beginning of pregnancy is associated with disease flares and preterm delivery in women with rheumatoid arthritis. Front Pharmacol. 2022 (Aug 3). Doi: 10.3389/fphar.2022.887462

Key clinical point: Discontinuation of biologic disease-modifying antirheumatic drugs (bDMARD) upon testing positive for pregnancy is associated with and a major risk factor for disease flare during pregnancy in a large proportion of women with rheumatoid arthritis (RA) and good disease control prior to conception.

Major finding: Overall, flare was reported by 37% of patients during pregnancy and was associated with discontinuing bDMARD upon testing positive for pregnancy (odds ratio [OR] 2.857; P  =  .034) and previous use of >1 bDMARD (OR 4.1; P  =  .019). Patients with vs without disease flare during pregnancy were more likely to report preterm delivery (27% vs 7%; OR 4.625; P  =  .034).

Study details: This study analyzed the retrospectively collected data of 73 pregnancies in 63 women with RA and good disease control during conception who were prospectively followed through their pregnancies.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Gerardi MC et al. Stopping bDMARDs at the beginning of pregnancy is associated with disease flares and preterm delivery in women with rheumatoid arthritis. Front Pharmacol. 2022 (Aug 3). Doi: 10.3389/fphar.2022.887462

Key clinical point: Discontinuation of biologic disease-modifying antirheumatic drugs (bDMARD) upon testing positive for pregnancy is associated with and a major risk factor for disease flare during pregnancy in a large proportion of women with rheumatoid arthritis (RA) and good disease control prior to conception.

Major finding: Overall, flare was reported by 37% of patients during pregnancy and was associated with discontinuing bDMARD upon testing positive for pregnancy (odds ratio [OR] 2.857; P  =  .034) and previous use of >1 bDMARD (OR 4.1; P  =  .019). Patients with vs without disease flare during pregnancy were more likely to report preterm delivery (27% vs 7%; OR 4.625; P  =  .034).

Study details: This study analyzed the retrospectively collected data of 73 pregnancies in 63 women with RA and good disease control during conception who were prospectively followed through their pregnancies.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Gerardi MC et al. Stopping bDMARDs at the beginning of pregnancy is associated with disease flares and preterm delivery in women with rheumatoid arthritis. Front Pharmacol. 2022 (Aug 3). Doi: 10.3389/fphar.2022.887462

Key clinical point: Patients with seropositive rheumatoid arthritis (RA) treated with first-line biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD), particularly tofacitinib, were at an increased risk for herpes zoster (HZ).

Major finding: Overall, the risk for HZ was significantly higher in patients receiving tofacitinib (adjusted hazard ratio [aHR] 2.46; P < .001), infliximab (aHR 1.36; P  =  .017), or adalimumab (aHR 1.29; P  =  .032) vs abatacept, with tofacitinib also increasing the risk for incident (aHR 1.99; P  =  .011) and recurrent (aHR 3.69; P < .001) HZ in patients without prior history of HZ.

Study details: This was a cohort study including 11,720 patients with seropositive RA who received first-line bDMARD or tsDMARD.

Disclosures: This study was supported by the Ministry of Health Welfare, Republic of Korea. The authors declared no conflicts of interest.

Source: Jeong S et al. Incident and recurrent herpes zoster for first-line bDMARD and tsDMARD users in seropositive rheumatoid arthritis patients: a nationwide cohort study. Arthritis Res Ther. 2022;24:180 (Jul 28). Doi: 10.1186/s13075-022-02871-1

Key clinical point: Patients with seropositive rheumatoid arthritis (RA) treated with first-line biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD), particularly tofacitinib, were at an increased risk for herpes zoster (HZ).

Major finding: Overall, the risk for HZ was significantly higher in patients receiving tofacitinib (adjusted hazard ratio [aHR] 2.46; P < .001), infliximab (aHR 1.36; P  =  .017), or adalimumab (aHR 1.29; P  =  .032) vs abatacept, with tofacitinib also increasing the risk for incident (aHR 1.99; P  =  .011) and recurrent (aHR 3.69; P < .001) HZ in patients without prior history of HZ.

Study details: This was a cohort study including 11,720 patients with seropositive RA who received first-line bDMARD or tsDMARD.

Disclosures: This study was supported by the Ministry of Health Welfare, Republic of Korea. The authors declared no conflicts of interest.

Source: Jeong S et al. Incident and recurrent herpes zoster for first-line bDMARD and tsDMARD users in seropositive rheumatoid arthritis patients: a nationwide cohort study. Arthritis Res Ther. 2022;24:180 (Jul 28). Doi: 10.1186/s13075-022-02871-1

Key clinical point: Patients with seropositive rheumatoid arthritis (RA) treated with first-line biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD), particularly tofacitinib, were at an increased risk for herpes zoster (HZ).

Major finding: Overall, the risk for HZ was significantly higher in patients receiving tofacitinib (adjusted hazard ratio [aHR] 2.46; P < .001), infliximab (aHR 1.36; P  =  .017), or adalimumab (aHR 1.29; P  =  .032) vs abatacept, with tofacitinib also increasing the risk for incident (aHR 1.99; P  =  .011) and recurrent (aHR 3.69; P < .001) HZ in patients without prior history of HZ.

Study details: This was a cohort study including 11,720 patients with seropositive RA who received first-line bDMARD or tsDMARD.

Disclosures: This study was supported by the Ministry of Health Welfare, Republic of Korea. The authors declared no conflicts of interest.

Source: Jeong S et al. Incident and recurrent herpes zoster for first-line bDMARD and tsDMARD users in seropositive rheumatoid arthritis patients: a nationwide cohort study. Arthritis Res Ther. 2022;24:180 (Jul 28). Doi: 10.1186/s13075-022-02871-1