Rheumatology

MANCHESTER, ENGLAND – Janus kinase (JAK) inhibitors may be associated with a higher risk for cancer relative to tumor necrosis factor (TNF) inhibitors, according to a meta-analysis reported at the annual meeting of the British Society for Rheumatology.

Looking at all phase 2, 3, and 4 trials and long-term extension studies across the indications of rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease, and atopic dermatitis, the risk ratio for any cancer developing was 1.63 when compared with anti-TNF therapy (95% confidence interval, 1.27-2.09).

Sara Freeman/MDedge News

By comparison, JAK inhibitor use was not significantly associated with any greater risk for cancer than methotrexate (RR, 1.06; 95% confidence interval, 0.58-1.94) or placebo (RR, 1.16; 95% CI, 0.75-1.80).

“Our data suggests that rather than JAK inhibitors necessarily being harmful, it could be more a case of TNF inhibitors being protective,” said Christopher Stovin, MBChB, a specialist registrar in rheumatology at the Princess Royal University Hospital, King’s College Hospital NHS Trust, London.

“We should stress that these are rare events in our study, roughly around 1 in every 100 patient-years of exposure,” Dr. Stovin said.

“Despite having over 80,000 years of patient exposure, the median follow-up duration for JAK inhibitors was still only 118 weeks, which for cancers [that] obviously have long latency periods is still a relatively small duration of time,” the researcher added.

“People worry about the drugs. But there is a possibility that [a] disturbed immune system plays a role per se in development of cancers,” consultant rheumatologist Anurag Bharadwaj, MD, DM, said in an interview.

“Although there are studies which attribute increased risk of cancer to different DMARDs [disease-modifying antirheumatic drugs] and biologics like TNF, but on other hand, it’s maybe that we are giving these drugs to patients who have got more serious immunological disease,” suggested Bharadwaj, who serves as the clinical lead for rheumatology at Basildon (England) Hospital, Mid & South Essex Foundation Trust.

“So, a possibility may be that the more severe or the more active the immunological inflammatory disease, the higher the chance of cancer, and these are the patients who go for the stronger medications,” Dr. Bharadwaj said.

There is an “immunological window of opportunity” when treating these inflammatory diseases, said Dr. Bharadwaj, noting that the first few months of treatment are vital. “For all immunological diseases, the more quickly you bring the immunological abnormality down, the chances of long-term complications go down, including [possibly that the] chances of cancer go down, chances of cardiovascular disease go down, and chances of lung disease go down. Hit it early, hit it hard.”

Concern over a possible higher risk for cancer with JAK inhibitors than with TNF inhibitors was raised following the release of data from the ORAL Surveillance trial, a postmarketing trial of tofacitinib (Xeljanz) that had been mandated by the Food and Drug Administration.

“This was a study looking at the coprimary endpoints of malignancy and major adverse cardiovascular events, and it was enriched with patients over the age of 50, with one additional cardiac risk factor, designed to amplify the detection of these rare events,” Dr. Stovin said.

“There was a signal of an increased risk of malignancy in the tofacitinib group, and this led to the FDA issuing a [boxed warning for all licensed JAK inhibitors] at that time,” he added.

Dr. Stovin and colleagues aimed to determine what, if any, cancer risk was associated with all available JAK inhibitors relative to placebo, TNF inhibitors, and methotrexate.

In all, data from 62 randomized controlled trials and 14 long-term extension studies were included in the meta-analysis, accounting for 82,366 patient years of follow-up. The JAK inhibitors analyzed included tofacitinib, baricitinib (Olumiant), upadacitinib (Rinvoq), filgotinib (Jyseleca), and peficitinib (Smyraf). (Filgotinib and peficitinib have not been approved by the FDA.)

The researchers performed sensitivity analyses that excluded cancers detected within the first 6 months of treatment, the use of higher than licensed JAK inhibitor doses, and patients with non-rheumatoid arthritis diagnoses, but the results remained largely unchanged, Dr. Stovin reported.  

“Perhaps not surprisingly, when we removed ORAL Surveillance” from the analysis comparing JAK inhibitors and TNF inhibitors, “we lost statistical significance,” he said.

“Longitudinal observational data is needed but currently remains limited,” Dr. Stovin concluded.

Dr. Stovin and Dr. Bharadwaj reported no relevant financial relationships. The meta-analysis was independently supported. Dr. Bharadwaj was not involved in the study and provided comment ahead of the presentation.

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

MANCHESTER, ENGLAND – Janus kinase (JAK) inhibitors may be associated with a higher risk for cancer relative to tumor necrosis factor (TNF) inhibitors, according to a meta-analysis reported at the annual meeting of the British Society for Rheumatology.

Looking at all phase 2, 3, and 4 trials and long-term extension studies across the indications of rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease, and atopic dermatitis, the risk ratio for any cancer developing was 1.63 when compared with anti-TNF therapy (95% confidence interval, 1.27-2.09).

Sara Freeman/MDedge News

By comparison, JAK inhibitor use was not significantly associated with any greater risk for cancer than methotrexate (RR, 1.06; 95% confidence interval, 0.58-1.94) or placebo (RR, 1.16; 95% CI, 0.75-1.80).

“Our data suggests that rather than JAK inhibitors necessarily being harmful, it could be more a case of TNF inhibitors being protective,” said Christopher Stovin, MBChB, a specialist registrar in rheumatology at the Princess Royal University Hospital, King’s College Hospital NHS Trust, London.

“We should stress that these are rare events in our study, roughly around 1 in every 100 patient-years of exposure,” Dr. Stovin said.

“Despite having over 80,000 years of patient exposure, the median follow-up duration for JAK inhibitors was still only 118 weeks, which for cancers [that] obviously have long latency periods is still a relatively small duration of time,” the researcher added.

“People worry about the drugs. But there is a possibility that [a] disturbed immune system plays a role per se in development of cancers,” consultant rheumatologist Anurag Bharadwaj, MD, DM, said in an interview.

“Although there are studies which attribute increased risk of cancer to different DMARDs [disease-modifying antirheumatic drugs] and biologics like TNF, but on other hand, it’s maybe that we are giving these drugs to patients who have got more serious immunological disease,” suggested Bharadwaj, who serves as the clinical lead for rheumatology at Basildon (England) Hospital, Mid & South Essex Foundation Trust.

“So, a possibility may be that the more severe or the more active the immunological inflammatory disease, the higher the chance of cancer, and these are the patients who go for the stronger medications,” Dr. Bharadwaj said.

There is an “immunological window of opportunity” when treating these inflammatory diseases, said Dr. Bharadwaj, noting that the first few months of treatment are vital. “For all immunological diseases, the more quickly you bring the immunological abnormality down, the chances of long-term complications go down, including [possibly that the] chances of cancer go down, chances of cardiovascular disease go down, and chances of lung disease go down. Hit it early, hit it hard.”

Concern over a possible higher risk for cancer with JAK inhibitors than with TNF inhibitors was raised following the release of data from the ORAL Surveillance trial, a postmarketing trial of tofacitinib (Xeljanz) that had been mandated by the Food and Drug Administration.

“This was a study looking at the coprimary endpoints of malignancy and major adverse cardiovascular events, and it was enriched with patients over the age of 50, with one additional cardiac risk factor, designed to amplify the detection of these rare events,” Dr. Stovin said.

“There was a signal of an increased risk of malignancy in the tofacitinib group, and this led to the FDA issuing a [boxed warning for all licensed JAK inhibitors] at that time,” he added.

Dr. Stovin and colleagues aimed to determine what, if any, cancer risk was associated with all available JAK inhibitors relative to placebo, TNF inhibitors, and methotrexate.

In all, data from 62 randomized controlled trials and 14 long-term extension studies were included in the meta-analysis, accounting for 82,366 patient years of follow-up. The JAK inhibitors analyzed included tofacitinib, baricitinib (Olumiant), upadacitinib (Rinvoq), filgotinib (Jyseleca), and peficitinib (Smyraf). (Filgotinib and peficitinib have not been approved by the FDA.)

The researchers performed sensitivity analyses that excluded cancers detected within the first 6 months of treatment, the use of higher than licensed JAK inhibitor doses, and patients with non-rheumatoid arthritis diagnoses, but the results remained largely unchanged, Dr. Stovin reported.  

“Perhaps not surprisingly, when we removed ORAL Surveillance” from the analysis comparing JAK inhibitors and TNF inhibitors, “we lost statistical significance,” he said.

“Longitudinal observational data is needed but currently remains limited,” Dr. Stovin concluded.

Dr. Stovin and Dr. Bharadwaj reported no relevant financial relationships. The meta-analysis was independently supported. Dr. Bharadwaj was not involved in the study and provided comment ahead of the presentation.

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

MANCHESTER, ENGLAND – Janus kinase (JAK) inhibitors may be associated with a higher risk for cancer relative to tumor necrosis factor (TNF) inhibitors, according to a meta-analysis reported at the annual meeting of the British Society for Rheumatology.

Looking at all phase 2, 3, and 4 trials and long-term extension studies across the indications of rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease, and atopic dermatitis, the risk ratio for any cancer developing was 1.63 when compared with anti-TNF therapy (95% confidence interval, 1.27-2.09).

Sara Freeman/MDedge News

By comparison, JAK inhibitor use was not significantly associated with any greater risk for cancer than methotrexate (RR, 1.06; 95% confidence interval, 0.58-1.94) or placebo (RR, 1.16; 95% CI, 0.75-1.80).

“Our data suggests that rather than JAK inhibitors necessarily being harmful, it could be more a case of TNF inhibitors being protective,” said Christopher Stovin, MBChB, a specialist registrar in rheumatology at the Princess Royal University Hospital, King’s College Hospital NHS Trust, London.

“We should stress that these are rare events in our study, roughly around 1 in every 100 patient-years of exposure,” Dr. Stovin said.

“Despite having over 80,000 years of patient exposure, the median follow-up duration for JAK inhibitors was still only 118 weeks, which for cancers [that] obviously have long latency periods is still a relatively small duration of time,” the researcher added.

“People worry about the drugs. But there is a possibility that [a] disturbed immune system plays a role per se in development of cancers,” consultant rheumatologist Anurag Bharadwaj, MD, DM, said in an interview.

“Although there are studies which attribute increased risk of cancer to different DMARDs [disease-modifying antirheumatic drugs] and biologics like TNF, but on other hand, it’s maybe that we are giving these drugs to patients who have got more serious immunological disease,” suggested Bharadwaj, who serves as the clinical lead for rheumatology at Basildon (England) Hospital, Mid & South Essex Foundation Trust.

“So, a possibility may be that the more severe or the more active the immunological inflammatory disease, the higher the chance of cancer, and these are the patients who go for the stronger medications,” Dr. Bharadwaj said.

There is an “immunological window of opportunity” when treating these inflammatory diseases, said Dr. Bharadwaj, noting that the first few months of treatment are vital. “For all immunological diseases, the more quickly you bring the immunological abnormality down, the chances of long-term complications go down, including [possibly that the] chances of cancer go down, chances of cardiovascular disease go down, and chances of lung disease go down. Hit it early, hit it hard.”

Concern over a possible higher risk for cancer with JAK inhibitors than with TNF inhibitors was raised following the release of data from the ORAL Surveillance trial, a postmarketing trial of tofacitinib (Xeljanz) that had been mandated by the Food and Drug Administration.

“This was a study looking at the coprimary endpoints of malignancy and major adverse cardiovascular events, and it was enriched with patients over the age of 50, with one additional cardiac risk factor, designed to amplify the detection of these rare events,” Dr. Stovin said.

“There was a signal of an increased risk of malignancy in the tofacitinib group, and this led to the FDA issuing a [boxed warning for all licensed JAK inhibitors] at that time,” he added.

Dr. Stovin and colleagues aimed to determine what, if any, cancer risk was associated with all available JAK inhibitors relative to placebo, TNF inhibitors, and methotrexate.

In all, data from 62 randomized controlled trials and 14 long-term extension studies were included in the meta-analysis, accounting for 82,366 patient years of follow-up. The JAK inhibitors analyzed included tofacitinib, baricitinib (Olumiant), upadacitinib (Rinvoq), filgotinib (Jyseleca), and peficitinib (Smyraf). (Filgotinib and peficitinib have not been approved by the FDA.)

The researchers performed sensitivity analyses that excluded cancers detected within the first 6 months of treatment, the use of higher than licensed JAK inhibitor doses, and patients with non-rheumatoid arthritis diagnoses, but the results remained largely unchanged, Dr. Stovin reported.  

“Perhaps not surprisingly, when we removed ORAL Surveillance” from the analysis comparing JAK inhibitors and TNF inhibitors, “we lost statistical significance,” he said.

“Longitudinal observational data is needed but currently remains limited,” Dr. Stovin concluded.

Dr. Stovin and Dr. Bharadwaj reported no relevant financial relationships. The meta-analysis was independently supported. Dr. Bharadwaj was not involved in the study and provided comment ahead of the presentation.

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

MANCHESTER, ENGLAND – Rheumatoid arthritis patients are no more likely to have a heart attack if they are treated with an interleukin-6 inhibitor (IL-6i) than if they are treated with a tumor necrosis factor inhibitor (TNFi), according to data presented at the British Society for Rheumatology annual meeting.

Results of a large analysis from the long-running British Society for Rheumatology Biologics Register–Rheumatoid Arthritis (BSRBR-RA) found no statistical difference in the rate of myocardial infarction (MI), considering treatment in almost 21,000 patients. The overall propensity-score adjusted hazard ratio for MI risk comparing TNFi and IL-6i was 0.77, but the 95% confidence interval crossed the line for statistical significance.

“This result reassures patients and clinical teams about the long-term treatment effects on myocardial infarction in a real-world setting,” said Tian Zixing, a PhD student at the University of Manchester (England).

Sara Freeman/MDedge News

“Patients with rheumatoid arthritis have an increased risk of myocardial infarction, compared to the general population,” Ms. Tian explained. However, this risk has been “considerably improved” with biologic treatment of rheumatoid arthritis, notably with the TNFi drugs vs. nonbiologic disease-modifying antirheumatic drugs.

The reasoning behind the current analysis was to see if there was any risk associated with IL-6i, as these drugs have been noted to increase low-density cholesterol levels, which in turn can raise the risk for MI.

The study population consisted of all patients registered in the BSRBR-RA over the past 20 years who had started treatment with one of the many TNFi drugs available in the UK – adalimumab (Humira and biosimilars), etanercept (Enbrel), infliximab (Remicade and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi) – or the two available drugs that target the effects of IL-6 – tocilizumab (RoActemra, but Actemra in the U.S.), which targets IL-6 itself, and sarilumab (Kevzara), which targets the IL-6 receptor.

Clinical follow-up forms, death certificates, and patient reports confirmed by the clinical team were used to identify patients who experienced a MI, but only MIs that occurred while on treatment were counted.

More than 30,000 lines of therapy in 20,898 patients were recorded. Ms. Tian noted that most (> 90%) patients had been treated with a TNFi across all lines of therapy.

“It is very important to consider the treatment sequence,” she said. “Most patients start first-line treatment with a TNF inhibitor, with only a few patients starting an IL-6 inhibitor,” she noted. “IL-6 inhibitors are more commonly used in the later stages of disease, when more cardiovascular risk factors have accumulated.”

Thus, to ensure that the MI risk was fairly evaluated, the statistical analyses compared TNFi and IL-6i according to the line of treatment. “That means only patients on their first-line treatment will be compared to each other, and only those on their second-line treatment will be compared to each other, and so on,” Ms. Tian explained.

Baseline characteristics were broadly similar for patients treated with TNFi and IL-6i drugs, except for hyperlipidemia, which was higher in patients treated with an IL-6i. Nevertheless, there was no suggestion of any difference in the MI rates after adjustment for cardiovascular risk factors.

There are a lot of strengths to these data, but of course the possibilities of residual confounding and confounding by indication exist, Ms. Tian said. There were also missing data that had to be imputed.

“There has been quite a bit around interleukin-1 blockers being cardiovascular protective,” observed Kenneth Baker, MBChB, PhD, who chaired the RA oral abstracts session during which Ms. Tian presented the findings.

“IL-6 is quite good at suppressing CRP [C-reactive protein],” added Dr. Baker, a senior clinical research fellow at Newcastle University and honorary consultant rheumatologist at Freeman Hospital, both in Newcastle upon Tyne, England.

“You’ve hypothesized or extrapolated that the differences in the lipid levels may not be relevant,” he said to Ms. Tian, “but do you think there might be an extra element going on here?” Maybe IL-6i drugs such as tocilizumab are better at suppressing inflammation, and that counterbalances the effects on lipids, he suggested.

Ms. Tian and Dr. Baker disclosed no relevant financial relationships. The BSRBR-RA is managed by the University of Manchester on behalf of the British Society for Rheumatology. The registry is supported by funding from multiple pharmaceutical companies, including AbbVie, Amgen, Celltrion Healthcare, Eli Lilly, Galapagos, Pfizer, Samsung Bioepis, and Sanofi, and in the past Hospira, Merck Sharp & Dohme, Roche, Sandoz, SOBI, and UCB.

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

MANCHESTER, ENGLAND – Rheumatoid arthritis patients are no more likely to have a heart attack if they are treated with an interleukin-6 inhibitor (IL-6i) than if they are treated with a tumor necrosis factor inhibitor (TNFi), according to data presented at the British Society for Rheumatology annual meeting.

Results of a large analysis from the long-running British Society for Rheumatology Biologics Register–Rheumatoid Arthritis (BSRBR-RA) found no statistical difference in the rate of myocardial infarction (MI), considering treatment in almost 21,000 patients. The overall propensity-score adjusted hazard ratio for MI risk comparing TNFi and IL-6i was 0.77, but the 95% confidence interval crossed the line for statistical significance.

“This result reassures patients and clinical teams about the long-term treatment effects on myocardial infarction in a real-world setting,” said Tian Zixing, a PhD student at the University of Manchester (England).

Sara Freeman/MDedge News

“Patients with rheumatoid arthritis have an increased risk of myocardial infarction, compared to the general population,” Ms. Tian explained. However, this risk has been “considerably improved” with biologic treatment of rheumatoid arthritis, notably with the TNFi drugs vs. nonbiologic disease-modifying antirheumatic drugs.

The reasoning behind the current analysis was to see if there was any risk associated with IL-6i, as these drugs have been noted to increase low-density cholesterol levels, which in turn can raise the risk for MI.

The study population consisted of all patients registered in the BSRBR-RA over the past 20 years who had started treatment with one of the many TNFi drugs available in the UK – adalimumab (Humira and biosimilars), etanercept (Enbrel), infliximab (Remicade and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi) – or the two available drugs that target the effects of IL-6 – tocilizumab (RoActemra, but Actemra in the U.S.), which targets IL-6 itself, and sarilumab (Kevzara), which targets the IL-6 receptor.

Clinical follow-up forms, death certificates, and patient reports confirmed by the clinical team were used to identify patients who experienced a MI, but only MIs that occurred while on treatment were counted.

More than 30,000 lines of therapy in 20,898 patients were recorded. Ms. Tian noted that most (> 90%) patients had been treated with a TNFi across all lines of therapy.

“It is very important to consider the treatment sequence,” she said. “Most patients start first-line treatment with a TNF inhibitor, with only a few patients starting an IL-6 inhibitor,” she noted. “IL-6 inhibitors are more commonly used in the later stages of disease, when more cardiovascular risk factors have accumulated.”

Thus, to ensure that the MI risk was fairly evaluated, the statistical analyses compared TNFi and IL-6i according to the line of treatment. “That means only patients on their first-line treatment will be compared to each other, and only those on their second-line treatment will be compared to each other, and so on,” Ms. Tian explained.

Baseline characteristics were broadly similar for patients treated with TNFi and IL-6i drugs, except for hyperlipidemia, which was higher in patients treated with an IL-6i. Nevertheless, there was no suggestion of any difference in the MI rates after adjustment for cardiovascular risk factors.

There are a lot of strengths to these data, but of course the possibilities of residual confounding and confounding by indication exist, Ms. Tian said. There were also missing data that had to be imputed.

“There has been quite a bit around interleukin-1 blockers being cardiovascular protective,” observed Kenneth Baker, MBChB, PhD, who chaired the RA oral abstracts session during which Ms. Tian presented the findings.

“IL-6 is quite good at suppressing CRP [C-reactive protein],” added Dr. Baker, a senior clinical research fellow at Newcastle University and honorary consultant rheumatologist at Freeman Hospital, both in Newcastle upon Tyne, England.

“You’ve hypothesized or extrapolated that the differences in the lipid levels may not be relevant,” he said to Ms. Tian, “but do you think there might be an extra element going on here?” Maybe IL-6i drugs such as tocilizumab are better at suppressing inflammation, and that counterbalances the effects on lipids, he suggested.

Ms. Tian and Dr. Baker disclosed no relevant financial relationships. The BSRBR-RA is managed by the University of Manchester on behalf of the British Society for Rheumatology. The registry is supported by funding from multiple pharmaceutical companies, including AbbVie, Amgen, Celltrion Healthcare, Eli Lilly, Galapagos, Pfizer, Samsung Bioepis, and Sanofi, and in the past Hospira, Merck Sharp & Dohme, Roche, Sandoz, SOBI, and UCB.

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

MANCHESTER, ENGLAND – Rheumatoid arthritis patients are no more likely to have a heart attack if they are treated with an interleukin-6 inhibitor (IL-6i) than if they are treated with a tumor necrosis factor inhibitor (TNFi), according to data presented at the British Society for Rheumatology annual meeting.

Results of a large analysis from the long-running British Society for Rheumatology Biologics Register–Rheumatoid Arthritis (BSRBR-RA) found no statistical difference in the rate of myocardial infarction (MI), considering treatment in almost 21,000 patients. The overall propensity-score adjusted hazard ratio for MI risk comparing TNFi and IL-6i was 0.77, but the 95% confidence interval crossed the line for statistical significance.

“This result reassures patients and clinical teams about the long-term treatment effects on myocardial infarction in a real-world setting,” said Tian Zixing, a PhD student at the University of Manchester (England).

Sara Freeman/MDedge News

“Patients with rheumatoid arthritis have an increased risk of myocardial infarction, compared to the general population,” Ms. Tian explained. However, this risk has been “considerably improved” with biologic treatment of rheumatoid arthritis, notably with the TNFi drugs vs. nonbiologic disease-modifying antirheumatic drugs.

The reasoning behind the current analysis was to see if there was any risk associated with IL-6i, as these drugs have been noted to increase low-density cholesterol levels, which in turn can raise the risk for MI.

The study population consisted of all patients registered in the BSRBR-RA over the past 20 years who had started treatment with one of the many TNFi drugs available in the UK – adalimumab (Humira and biosimilars), etanercept (Enbrel), infliximab (Remicade and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi) – or the two available drugs that target the effects of IL-6 – tocilizumab (RoActemra, but Actemra in the U.S.), which targets IL-6 itself, and sarilumab (Kevzara), which targets the IL-6 receptor.

Clinical follow-up forms, death certificates, and patient reports confirmed by the clinical team were used to identify patients who experienced a MI, but only MIs that occurred while on treatment were counted.

More than 30,000 lines of therapy in 20,898 patients were recorded. Ms. Tian noted that most (> 90%) patients had been treated with a TNFi across all lines of therapy.

“It is very important to consider the treatment sequence,” she said. “Most patients start first-line treatment with a TNF inhibitor, with only a few patients starting an IL-6 inhibitor,” she noted. “IL-6 inhibitors are more commonly used in the later stages of disease, when more cardiovascular risk factors have accumulated.”

Thus, to ensure that the MI risk was fairly evaluated, the statistical analyses compared TNFi and IL-6i according to the line of treatment. “That means only patients on their first-line treatment will be compared to each other, and only those on their second-line treatment will be compared to each other, and so on,” Ms. Tian explained.

Baseline characteristics were broadly similar for patients treated with TNFi and IL-6i drugs, except for hyperlipidemia, which was higher in patients treated with an IL-6i. Nevertheless, there was no suggestion of any difference in the MI rates after adjustment for cardiovascular risk factors.

There are a lot of strengths to these data, but of course the possibilities of residual confounding and confounding by indication exist, Ms. Tian said. There were also missing data that had to be imputed.

“There has been quite a bit around interleukin-1 blockers being cardiovascular protective,” observed Kenneth Baker, MBChB, PhD, who chaired the RA oral abstracts session during which Ms. Tian presented the findings.

“IL-6 is quite good at suppressing CRP [C-reactive protein],” added Dr. Baker, a senior clinical research fellow at Newcastle University and honorary consultant rheumatologist at Freeman Hospital, both in Newcastle upon Tyne, England.

“You’ve hypothesized or extrapolated that the differences in the lipid levels may not be relevant,” he said to Ms. Tian, “but do you think there might be an extra element going on here?” Maybe IL-6i drugs such as tocilizumab are better at suppressing inflammation, and that counterbalances the effects on lipids, he suggested.

Ms. Tian and Dr. Baker disclosed no relevant financial relationships. The BSRBR-RA is managed by the University of Manchester on behalf of the British Society for Rheumatology. The registry is supported by funding from multiple pharmaceutical companies, including AbbVie, Amgen, Celltrion Healthcare, Eli Lilly, Galapagos, Pfizer, Samsung Bioepis, and Sanofi, and in the past Hospira, Merck Sharp & Dohme, Roche, Sandoz, SOBI, and UCB.

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

Patients taking metformin for type 2 diabetes had a lower risk of developing osteoarthritis than did patients taking a sulfonylurea, according to a cohort study published in JAMA Network Open. The findings jibe with those seen in a 2022 systematic review of preclinical and observational human studies finding potentially protective effects of metformin on osteoarthritis.

“Our study provides further, robust epidemiological evidence that metformin may be associated with protection in the development and progression of osteoarthritis in individuals with type 2 diabetes,” wrote Matthew C. Baker, MD, MS, an assistant professor of medicine in immunology and rheumatology at Stanford (Calif.) University, and his colleagues.

Thinglass/iStock Editorial/Getty Images

The findings also fit with the results of a poster presented at the Osteoarthritis Research Society International 2023 World Congress, although that abstract’s findings did not reach statistical significance.

In the published study, the researchers analyzed deidentified claims data from Optum’s Clinformatics Data Mart Database between December 2003 and December 2019. The database includes more than 15 million people with private insurance or Medicare Advantage Part D but does not include people with Medicaid, thereby excluding people from lower socioeconomic groups.

The researchers included all patients who were at least 40 years old, had type 2 diabetes, were taking metformin, and had been enrolled in the database for at least 1 uninterrupted year. They excluded anyone with type 1 diabetes or a prior diagnosis of osteoarthritis, inflammatory arthritis, or joint replacement. The authors then compared the incidence of osteoarthritis and joint replacement in these 20,937 participants to 20,937 control participants who were taking a sulfonylurea, matched to those taking metformin on the basis of age, sex, race, a comorbidity score, and duration of treatment. More than half the overall population (58%) was male with an average age of 62.

Patients needed to be on either drug for at least 3 months, but those who were initially treated with metformin before later taking a sulfonylurea could also be included and contribute to both groups. Those who first took a sulfonylurea and later switched to metformin were included only for the sulfonylurea group and censored after their switch to ensure the sulfonylurea group had enough participants. The comparison was further adjusted for age, sex, race, ethnicity, geographic region, education, comorbidities, and outpatient visit frequency.

The results revealed that those who were taking metformin were 24% less likely to develop osteoarthritis at least 3 months after starting the medication than were those taking a sulfonylurea (P < .001). The rate of joint replacements was not significantly different between those taking metformin and those taking a sulfonylurea. These two results did not change in a sensitivity analysis that compared patients who only ever took metformin or a sulfonylurea (as opposed to those who took one drug before switching to the other).

“When stratified by prior exposure to metformin within the sulfonylurea group, the observed benefit associated with metformin ... was attenuated in the people treated with a sulfonylurea with prior exposure to metformin, compared with those treated with a sulfonylurea with no prior exposure to metformin,” the authors further reported. A possible reason for this finding is that those taking a sulfonylurea after having previously taken metformin gained some protection from the earlier metformin exposure, the authors hypothesized.

This observational study could not show a causative effect from the metformin, but the researchers speculated on potential mechanisms if a causative effect were present, based on past research.

”Several preclinical studies have suggested a protective association of metformin in osteoarthritis through activating AMP-activated protein kinase signaling, decreasing the level of matrix metalloproteinase, increasing autophagy and reducing chondrocyte apoptosis, and augmenting chondroprotective and anti-inflammatory properties of mesenchymal stem cells,” the authors wrote.

Among this study’s limitations, however, was the lack of data on body mass index, which is associated with osteoarthritis in the literature and may differ between patients taking metformin versus a sulfonylurea. The researchers also did not have data on physical activity or a history of trauma to the joints, though there’s no reason to think these rates might differ between those taking one or the other medication.

Another substantial limitation is that all patients had type 2 diabetes, making it impossible to determine whether a similar protective effect from metformin might exist in people without diabetes.

Nonsignificant lower risk for posttraumatic knee osteoarthritis

Similar to the published study, the OARSI poster compared 5-year odds of incident osteoarthritis or total knee replacement surgery between patients taking metformin and those taking sulfonylureas, but it focused on younger patients, aged 18-40 years, who underwent anterior cruciate ligament or meniscus surgery.

Using data from MarketScan commercial insurance claims databases between 2006 and 2020, the authors identified 2,376 participants who were taking metformin or a sulfonylurea when they underwent their surgery or began taking it in the 6 months after their surgery. More than half the participants were female (57%) with an average age of 35.

Within 5 years, 10.8% of those taking metformin developed osteoarthritis, compared with 17.9% of those taking a sulfonylurea. In addition, 3% of those taking metformin underwent a total knee replacement, compared with 5.3% of those taking a sulfonylurea. After adjustment for age, sex, obesity, and a history of chronic kidney disease, liver disease, and depression, however, both risk difference and odds ratios were not statistically significant.

Risk of osteoarthritis was 17% lower in patients taking metformin (95% confidence interval, –0.18 to 0.09), whose odds of osteoarthritis were approximately half the odds of those taking a sulfonylurea (OR, 0.5; 95% CI, 0.21-1.67). Risk of a total knee replacement was 10% lower in metformin users (95% CI, –0.28 to 0.08) with a similar reduction in odds, compared with those taking a sulfonylurea (OR, 0.53; 95% CI, 0.2-1.44).

In this study, the researchers did not specifically determine whether the participants were diagnosed with diabetes, but they assumed all, or at least most, were, according to S. Reza Jafarzadeh, PhD, DVM, an assistant professor of medicine at Boston University.

“The goal was not to only focus on the diabetes population, but on people who received that exposure [of metformin or sulfonylureas],” Dr. Jafarzadeh said in an interview. Dr. Jafarzadeh noted that a larger randomized controlled trial is underway to look at whether metformin reduces the risk of osteoarthritis independent of whether a patient has diabetes.

The published study was funded by grants from the National Institutes of Health, the Department of Veterans Affairs, and Stanford University, and the authors reported no disclosures. The poster at OARSI was funded by NIH and the Arthritis Foundation, and the authors reported no disclosures.

Patients taking metformin for type 2 diabetes had a lower risk of developing osteoarthritis than did patients taking a sulfonylurea, according to a cohort study published in JAMA Network Open. The findings jibe with those seen in a 2022 systematic review of preclinical and observational human studies finding potentially protective effects of metformin on osteoarthritis.

“Our study provides further, robust epidemiological evidence that metformin may be associated with protection in the development and progression of osteoarthritis in individuals with type 2 diabetes,” wrote Matthew C. Baker, MD, MS, an assistant professor of medicine in immunology and rheumatology at Stanford (Calif.) University, and his colleagues.

Thinglass/iStock Editorial/Getty Images

The findings also fit with the results of a poster presented at the Osteoarthritis Research Society International 2023 World Congress, although that abstract’s findings did not reach statistical significance.

In the published study, the researchers analyzed deidentified claims data from Optum’s Clinformatics Data Mart Database between December 2003 and December 2019. The database includes more than 15 million people with private insurance or Medicare Advantage Part D but does not include people with Medicaid, thereby excluding people from lower socioeconomic groups.

The researchers included all patients who were at least 40 years old, had type 2 diabetes, were taking metformin, and had been enrolled in the database for at least 1 uninterrupted year. They excluded anyone with type 1 diabetes or a prior diagnosis of osteoarthritis, inflammatory arthritis, or joint replacement. The authors then compared the incidence of osteoarthritis and joint replacement in these 20,937 participants to 20,937 control participants who were taking a sulfonylurea, matched to those taking metformin on the basis of age, sex, race, a comorbidity score, and duration of treatment. More than half the overall population (58%) was male with an average age of 62.

Patients needed to be on either drug for at least 3 months, but those who were initially treated with metformin before later taking a sulfonylurea could also be included and contribute to both groups. Those who first took a sulfonylurea and later switched to metformin were included only for the sulfonylurea group and censored after their switch to ensure the sulfonylurea group had enough participants. The comparison was further adjusted for age, sex, race, ethnicity, geographic region, education, comorbidities, and outpatient visit frequency.

The results revealed that those who were taking metformin were 24% less likely to develop osteoarthritis at least 3 months after starting the medication than were those taking a sulfonylurea (P < .001). The rate of joint replacements was not significantly different between those taking metformin and those taking a sulfonylurea. These two results did not change in a sensitivity analysis that compared patients who only ever took metformin or a sulfonylurea (as opposed to those who took one drug before switching to the other).

“When stratified by prior exposure to metformin within the sulfonylurea group, the observed benefit associated with metformin ... was attenuated in the people treated with a sulfonylurea with prior exposure to metformin, compared with those treated with a sulfonylurea with no prior exposure to metformin,” the authors further reported. A possible reason for this finding is that those taking a sulfonylurea after having previously taken metformin gained some protection from the earlier metformin exposure, the authors hypothesized.

This observational study could not show a causative effect from the metformin, but the researchers speculated on potential mechanisms if a causative effect were present, based on past research.

”Several preclinical studies have suggested a protective association of metformin in osteoarthritis through activating AMP-activated protein kinase signaling, decreasing the level of matrix metalloproteinase, increasing autophagy and reducing chondrocyte apoptosis, and augmenting chondroprotective and anti-inflammatory properties of mesenchymal stem cells,” the authors wrote.

Among this study’s limitations, however, was the lack of data on body mass index, which is associated with osteoarthritis in the literature and may differ between patients taking metformin versus a sulfonylurea. The researchers also did not have data on physical activity or a history of trauma to the joints, though there’s no reason to think these rates might differ between those taking one or the other medication.

Another substantial limitation is that all patients had type 2 diabetes, making it impossible to determine whether a similar protective effect from metformin might exist in people without diabetes.

Nonsignificant lower risk for posttraumatic knee osteoarthritis

Similar to the published study, the OARSI poster compared 5-year odds of incident osteoarthritis or total knee replacement surgery between patients taking metformin and those taking sulfonylureas, but it focused on younger patients, aged 18-40 years, who underwent anterior cruciate ligament or meniscus surgery.

Using data from MarketScan commercial insurance claims databases between 2006 and 2020, the authors identified 2,376 participants who were taking metformin or a sulfonylurea when they underwent their surgery or began taking it in the 6 months after their surgery. More than half the participants were female (57%) with an average age of 35.

Within 5 years, 10.8% of those taking metformin developed osteoarthritis, compared with 17.9% of those taking a sulfonylurea. In addition, 3% of those taking metformin underwent a total knee replacement, compared with 5.3% of those taking a sulfonylurea. After adjustment for age, sex, obesity, and a history of chronic kidney disease, liver disease, and depression, however, both risk difference and odds ratios were not statistically significant.

Risk of osteoarthritis was 17% lower in patients taking metformin (95% confidence interval, –0.18 to 0.09), whose odds of osteoarthritis were approximately half the odds of those taking a sulfonylurea (OR, 0.5; 95% CI, 0.21-1.67). Risk of a total knee replacement was 10% lower in metformin users (95% CI, –0.28 to 0.08) with a similar reduction in odds, compared with those taking a sulfonylurea (OR, 0.53; 95% CI, 0.2-1.44).

In this study, the researchers did not specifically determine whether the participants were diagnosed with diabetes, but they assumed all, or at least most, were, according to S. Reza Jafarzadeh, PhD, DVM, an assistant professor of medicine at Boston University.

“The goal was not to only focus on the diabetes population, but on people who received that exposure [of metformin or sulfonylureas],” Dr. Jafarzadeh said in an interview. Dr. Jafarzadeh noted that a larger randomized controlled trial is underway to look at whether metformin reduces the risk of osteoarthritis independent of whether a patient has diabetes.

The published study was funded by grants from the National Institutes of Health, the Department of Veterans Affairs, and Stanford University, and the authors reported no disclosures. The poster at OARSI was funded by NIH and the Arthritis Foundation, and the authors reported no disclosures.

Patients taking metformin for type 2 diabetes had a lower risk of developing osteoarthritis than did patients taking a sulfonylurea, according to a cohort study published in JAMA Network Open. The findings jibe with those seen in a 2022 systematic review of preclinical and observational human studies finding potentially protective effects of metformin on osteoarthritis.

“Our study provides further, robust epidemiological evidence that metformin may be associated with protection in the development and progression of osteoarthritis in individuals with type 2 diabetes,” wrote Matthew C. Baker, MD, MS, an assistant professor of medicine in immunology and rheumatology at Stanford (Calif.) University, and his colleagues.

Thinglass/iStock Editorial/Getty Images

The findings also fit with the results of a poster presented at the Osteoarthritis Research Society International 2023 World Congress, although that abstract’s findings did not reach statistical significance.

In the published study, the researchers analyzed deidentified claims data from Optum’s Clinformatics Data Mart Database between December 2003 and December 2019. The database includes more than 15 million people with private insurance or Medicare Advantage Part D but does not include people with Medicaid, thereby excluding people from lower socioeconomic groups.

The researchers included all patients who were at least 40 years old, had type 2 diabetes, were taking metformin, and had been enrolled in the database for at least 1 uninterrupted year. They excluded anyone with type 1 diabetes or a prior diagnosis of osteoarthritis, inflammatory arthritis, or joint replacement. The authors then compared the incidence of osteoarthritis and joint replacement in these 20,937 participants to 20,937 control participants who were taking a sulfonylurea, matched to those taking metformin on the basis of age, sex, race, a comorbidity score, and duration of treatment. More than half the overall population (58%) was male with an average age of 62.

Patients needed to be on either drug for at least 3 months, but those who were initially treated with metformin before later taking a sulfonylurea could also be included and contribute to both groups. Those who first took a sulfonylurea and later switched to metformin were included only for the sulfonylurea group and censored after their switch to ensure the sulfonylurea group had enough participants. The comparison was further adjusted for age, sex, race, ethnicity, geographic region, education, comorbidities, and outpatient visit frequency.

The results revealed that those who were taking metformin were 24% less likely to develop osteoarthritis at least 3 months after starting the medication than were those taking a sulfonylurea (P < .001). The rate of joint replacements was not significantly different between those taking metformin and those taking a sulfonylurea. These two results did not change in a sensitivity analysis that compared patients who only ever took metformin or a sulfonylurea (as opposed to those who took one drug before switching to the other).

“When stratified by prior exposure to metformin within the sulfonylurea group, the observed benefit associated with metformin ... was attenuated in the people treated with a sulfonylurea with prior exposure to metformin, compared with those treated with a sulfonylurea with no prior exposure to metformin,” the authors further reported. A possible reason for this finding is that those taking a sulfonylurea after having previously taken metformin gained some protection from the earlier metformin exposure, the authors hypothesized.

This observational study could not show a causative effect from the metformin, but the researchers speculated on potential mechanisms if a causative effect were present, based on past research.

”Several preclinical studies have suggested a protective association of metformin in osteoarthritis through activating AMP-activated protein kinase signaling, decreasing the level of matrix metalloproteinase, increasing autophagy and reducing chondrocyte apoptosis, and augmenting chondroprotective and anti-inflammatory properties of mesenchymal stem cells,” the authors wrote.

Among this study’s limitations, however, was the lack of data on body mass index, which is associated with osteoarthritis in the literature and may differ between patients taking metformin versus a sulfonylurea. The researchers also did not have data on physical activity or a history of trauma to the joints, though there’s no reason to think these rates might differ between those taking one or the other medication.

Another substantial limitation is that all patients had type 2 diabetes, making it impossible to determine whether a similar protective effect from metformin might exist in people without diabetes.

Nonsignificant lower risk for posttraumatic knee osteoarthritis

Similar to the published study, the OARSI poster compared 5-year odds of incident osteoarthritis or total knee replacement surgery between patients taking metformin and those taking sulfonylureas, but it focused on younger patients, aged 18-40 years, who underwent anterior cruciate ligament or meniscus surgery.

Using data from MarketScan commercial insurance claims databases between 2006 and 2020, the authors identified 2,376 participants who were taking metformin or a sulfonylurea when they underwent their surgery or began taking it in the 6 months after their surgery. More than half the participants were female (57%) with an average age of 35.

Within 5 years, 10.8% of those taking metformin developed osteoarthritis, compared with 17.9% of those taking a sulfonylurea. In addition, 3% of those taking metformin underwent a total knee replacement, compared with 5.3% of those taking a sulfonylurea. After adjustment for age, sex, obesity, and a history of chronic kidney disease, liver disease, and depression, however, both risk difference and odds ratios were not statistically significant.

Risk of osteoarthritis was 17% lower in patients taking metformin (95% confidence interval, –0.18 to 0.09), whose odds of osteoarthritis were approximately half the odds of those taking a sulfonylurea (OR, 0.5; 95% CI, 0.21-1.67). Risk of a total knee replacement was 10% lower in metformin users (95% CI, –0.28 to 0.08) with a similar reduction in odds, compared with those taking a sulfonylurea (OR, 0.53; 95% CI, 0.2-1.44).

In this study, the researchers did not specifically determine whether the participants were diagnosed with diabetes, but they assumed all, or at least most, were, according to S. Reza Jafarzadeh, PhD, DVM, an assistant professor of medicine at Boston University.

“The goal was not to only focus on the diabetes population, but on people who received that exposure [of metformin or sulfonylureas],” Dr. Jafarzadeh said in an interview. Dr. Jafarzadeh noted that a larger randomized controlled trial is underway to look at whether metformin reduces the risk of osteoarthritis independent of whether a patient has diabetes.

The published study was funded by grants from the National Institutes of Health, the Department of Veterans Affairs, and Stanford University, and the authors reported no disclosures. The poster at OARSI was funded by NIH and the Arthritis Foundation, and the authors reported no disclosures.

Nasal damage from cocaine use can be misdiagnosed as a rare, nonthreatening nasal disease, according to researchers from the United Kingdom.

Granulomatosis with polyangiitis (GPA), a disorder which causes inflammation in the nose, sinuses, throat, lungs, and kidneys, can have similar symptoms to cocaine-induced vasculitis, the researchers wrote. Drug testing can help identify patients who have cocaine-induced disease, they argued.

“Patients with destructive nasal lesions, especially young patients, should have urine toxicology performed for cocaine before diagnosing GPA and considering immunosuppressive therapy,” the authors wrote.

The paper was published in Rheumatology Advances in Practice.

Cocaine is the second-most popular drug in the United Kingdom, with 2.0% of people aged 16-59 years reporting using the drug in the past year. In the United States, about 1.7% of people aged 12 years and older (about 4.8 million people) used cocaine in the last 12 months, according to the 2021 National Survey on Drug Use and Health. The drug can cause midline destructive lesions, skin rash, and other vascular problems, and it can also trigger the production of antineutrophil cytoplasmic antibodies (ANCA) that lead to a clinical presentation that mimics GPA, which can make diagnosis more difficult. Treating cocaine-induced disease with immunosuppressant medication can be ineffective if the patient does not stop using the drug, and can have dangerous side effects, previous case studies suggest.

To better understand cocaine-induced disease, researchers conducted a review of patients who visited vasculitis clinics at Queen Elizabeth Hospital in Birmingham, England, and at the Royal Free Hospital in London between 2016 and 2021. They identified 42 patients with GPA-like symptoms who disclosed cocaine use or tested positive for the drug in urine toxicology test. The study included 23 men, 18 women, and 1 individual who did not identify with either gender. The median age was 41 years, and most patients were white.

Of those who underwent drug testing, more than 85% were positive. Nine patients who denied ever using cocaine were positive for the drug and 11 patients who said they were ex-users also tested positive via urine analysis. During clinical examinations, 30 patients had evidence of septal perforation, of which 6 had oronasal fistulas. Most patients’ symptoms were limited to the upper respiratory tract, though 12 did have other systemic symptoms, including skin lesions, joint pain, breathlessness, fatigue, and diplopia. Of the patients who received blood tests for ANCA, 87.5% tested positive for the antibodies.

The researchers noted that patients who continued cocaine use did not see improvement of symptoms, even if they were treated with immunosuppressant drugs.

“The experience in our two different centers suggests that discontinuation of cocaine is required to manage patients and that symptoms will persist despite immunosuppression if there is ongoing cocaine use,” the authors wrote.

“It can feel like chasing your tail at times if you’re trying to treat the inflammation but the real culprit – what’s driving the inflammation – is persistent,” Lindsay S. Lally, MD, a rheumatologist at the Hospital for Special Surgery in New York, said in an interview. She was not involved with the work.

Dr. Lally said the paper had a decent-sized cohort, and “helps us recognize that cocaine use is probably an under-recognized mimic of GPA, even though it’s something we all learn about and talk about.” She added that routine toxicology screening for patients deserves some consideration, though asking patients to complete a drug test could also undermine trust in the doctor-patient relationship. Patients who deny cocaine use may leave the office without providing a urine sample.

If Dr. Lally does suspect cocaine may be the cause of a patient’s systems, having a candid conversation with the patient may have a better chance at getting a patient to open up about their potential drug use. In practice, this means explaining “why it’s so important for me as their partner in this treatment to understand what factors are at play, and how dangerous it could potentially be if I was giving strong immunosuppressive medications [for a condition] that is being induced by a drug,” she said. “I do think that partnership and talking to the patients, at least in many patients, is more helpful than sort of the ‘gotcha’ moment” that can happen with drug testing.

The study authors disclosed no relevant financial relationships. Dr. Lally reported receiving consulting fees from Amgen.

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

Nasal damage from cocaine use can be misdiagnosed as a rare, nonthreatening nasal disease, according to researchers from the United Kingdom.

Granulomatosis with polyangiitis (GPA), a disorder which causes inflammation in the nose, sinuses, throat, lungs, and kidneys, can have similar symptoms to cocaine-induced vasculitis, the researchers wrote. Drug testing can help identify patients who have cocaine-induced disease, they argued.

“Patients with destructive nasal lesions, especially young patients, should have urine toxicology performed for cocaine before diagnosing GPA and considering immunosuppressive therapy,” the authors wrote.

The paper was published in Rheumatology Advances in Practice.

Cocaine is the second-most popular drug in the United Kingdom, with 2.0% of people aged 16-59 years reporting using the drug in the past year. In the United States, about 1.7% of people aged 12 years and older (about 4.8 million people) used cocaine in the last 12 months, according to the 2021 National Survey on Drug Use and Health. The drug can cause midline destructive lesions, skin rash, and other vascular problems, and it can also trigger the production of antineutrophil cytoplasmic antibodies (ANCA) that lead to a clinical presentation that mimics GPA, which can make diagnosis more difficult. Treating cocaine-induced disease with immunosuppressant medication can be ineffective if the patient does not stop using the drug, and can have dangerous side effects, previous case studies suggest.

To better understand cocaine-induced disease, researchers conducted a review of patients who visited vasculitis clinics at Queen Elizabeth Hospital in Birmingham, England, and at the Royal Free Hospital in London between 2016 and 2021. They identified 42 patients with GPA-like symptoms who disclosed cocaine use or tested positive for the drug in urine toxicology test. The study included 23 men, 18 women, and 1 individual who did not identify with either gender. The median age was 41 years, and most patients were white.

Of those who underwent drug testing, more than 85% were positive. Nine patients who denied ever using cocaine were positive for the drug and 11 patients who said they were ex-users also tested positive via urine analysis. During clinical examinations, 30 patients had evidence of septal perforation, of which 6 had oronasal fistulas. Most patients’ symptoms were limited to the upper respiratory tract, though 12 did have other systemic symptoms, including skin lesions, joint pain, breathlessness, fatigue, and diplopia. Of the patients who received blood tests for ANCA, 87.5% tested positive for the antibodies.

The researchers noted that patients who continued cocaine use did not see improvement of symptoms, even if they were treated with immunosuppressant drugs.

“The experience in our two different centers suggests that discontinuation of cocaine is required to manage patients and that symptoms will persist despite immunosuppression if there is ongoing cocaine use,” the authors wrote.

“It can feel like chasing your tail at times if you’re trying to treat the inflammation but the real culprit – what’s driving the inflammation – is persistent,” Lindsay S. Lally, MD, a rheumatologist at the Hospital for Special Surgery in New York, said in an interview. She was not involved with the work.

Dr. Lally said the paper had a decent-sized cohort, and “helps us recognize that cocaine use is probably an under-recognized mimic of GPA, even though it’s something we all learn about and talk about.” She added that routine toxicology screening for patients deserves some consideration, though asking patients to complete a drug test could also undermine trust in the doctor-patient relationship. Patients who deny cocaine use may leave the office without providing a urine sample.

If Dr. Lally does suspect cocaine may be the cause of a patient’s systems, having a candid conversation with the patient may have a better chance at getting a patient to open up about their potential drug use. In practice, this means explaining “why it’s so important for me as their partner in this treatment to understand what factors are at play, and how dangerous it could potentially be if I was giving strong immunosuppressive medications [for a condition] that is being induced by a drug,” she said. “I do think that partnership and talking to the patients, at least in many patients, is more helpful than sort of the ‘gotcha’ moment” that can happen with drug testing.

The study authors disclosed no relevant financial relationships. Dr. Lally reported receiving consulting fees from Amgen.

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

Nasal damage from cocaine use can be misdiagnosed as a rare, nonthreatening nasal disease, according to researchers from the United Kingdom.

Granulomatosis with polyangiitis (GPA), a disorder which causes inflammation in the nose, sinuses, throat, lungs, and kidneys, can have similar symptoms to cocaine-induced vasculitis, the researchers wrote. Drug testing can help identify patients who have cocaine-induced disease, they argued.

“Patients with destructive nasal lesions, especially young patients, should have urine toxicology performed for cocaine before diagnosing GPA and considering immunosuppressive therapy,” the authors wrote.

The paper was published in Rheumatology Advances in Practice.

Cocaine is the second-most popular drug in the United Kingdom, with 2.0% of people aged 16-59 years reporting using the drug in the past year. In the United States, about 1.7% of people aged 12 years and older (about 4.8 million people) used cocaine in the last 12 months, according to the 2021 National Survey on Drug Use and Health. The drug can cause midline destructive lesions, skin rash, and other vascular problems, and it can also trigger the production of antineutrophil cytoplasmic antibodies (ANCA) that lead to a clinical presentation that mimics GPA, which can make diagnosis more difficult. Treating cocaine-induced disease with immunosuppressant medication can be ineffective if the patient does not stop using the drug, and can have dangerous side effects, previous case studies suggest.

To better understand cocaine-induced disease, researchers conducted a review of patients who visited vasculitis clinics at Queen Elizabeth Hospital in Birmingham, England, and at the Royal Free Hospital in London between 2016 and 2021. They identified 42 patients with GPA-like symptoms who disclosed cocaine use or tested positive for the drug in urine toxicology test. The study included 23 men, 18 women, and 1 individual who did not identify with either gender. The median age was 41 years, and most patients were white.

Of those who underwent drug testing, more than 85% were positive. Nine patients who denied ever using cocaine were positive for the drug and 11 patients who said they were ex-users also tested positive via urine analysis. During clinical examinations, 30 patients had evidence of septal perforation, of which 6 had oronasal fistulas. Most patients’ symptoms were limited to the upper respiratory tract, though 12 did have other systemic symptoms, including skin lesions, joint pain, breathlessness, fatigue, and diplopia. Of the patients who received blood tests for ANCA, 87.5% tested positive for the antibodies.

The researchers noted that patients who continued cocaine use did not see improvement of symptoms, even if they were treated with immunosuppressant drugs.

“The experience in our two different centers suggests that discontinuation of cocaine is required to manage patients and that symptoms will persist despite immunosuppression if there is ongoing cocaine use,” the authors wrote.

“It can feel like chasing your tail at times if you’re trying to treat the inflammation but the real culprit – what’s driving the inflammation – is persistent,” Lindsay S. Lally, MD, a rheumatologist at the Hospital for Special Surgery in New York, said in an interview. She was not involved with the work.

Dr. Lally said the paper had a decent-sized cohort, and “helps us recognize that cocaine use is probably an under-recognized mimic of GPA, even though it’s something we all learn about and talk about.” She added that routine toxicology screening for patients deserves some consideration, though asking patients to complete a drug test could also undermine trust in the doctor-patient relationship. Patients who deny cocaine use may leave the office without providing a urine sample.

If Dr. Lally does suspect cocaine may be the cause of a patient’s systems, having a candid conversation with the patient may have a better chance at getting a patient to open up about their potential drug use. In practice, this means explaining “why it’s so important for me as their partner in this treatment to understand what factors are at play, and how dangerous it could potentially be if I was giving strong immunosuppressive medications [for a condition] that is being induced by a drug,” she said. “I do think that partnership and talking to the patients, at least in many patients, is more helpful than sort of the ‘gotcha’ moment” that can happen with drug testing.

The study authors disclosed no relevant financial relationships. Dr. Lally reported receiving consulting fees from Amgen.

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

The investigational interleukin-17A inhibitor izokibep showed higher response rates across a number of symptoms in adults with psoriatic arthritis (PsA) in an extension of its phase 2 trial out to 46 weeks, according to an announcement reporting some of the long-term data by the drug’s developer, Acelyrin.

Izokibep is an antibody mimetic designed to inhibit IL-17A that the company says has “high potency and the potential for robust tissue penetration due to its small molecular size, about one-tenth the size of a monoclonal antibody.”

“Patients want both rapid and meaningful improvement of their symptoms, as well as lasting – and ideally improving – resolution of disease over time. Building on the 16-week data for izokibep reported at EULAR and ACR [American College of Rheumatology] last year, the 46-week data now show not only continued but marked improvements over time in key areas of psoriatic arthritis including joint pain, skin psoriasis, and enthesitis,” Philip J. Mease, MD, director of rheumatology research at the Swedish Medical Center and clinical professor at the University of Washington, both in Seattle, and an investigator in the izokibep PsA program, said in the announcement.

The phase 2 trial tested two doses of izokibep – 40 mg and 80 mg – given by subcutaneous injection every 2 weeks – against placebo in 135 adult patients with active PsA. For inclusion in the trial, patients had to have at least three swollen and at least three tender joints and an inadequate response to prior therapy including NSAIDs, conventional synthetic disease-modifying antirheumatic drugs, or tumor necrosis factor inhibitors. At week 16, the placebo group transitioned to 80 mg izokibep every 2 weeks and the trial treatment period continued for up to 46 weeks.

The trial’s primary endpoint of a 50% or higher level of improvement in ACR response criteria (ACR 50) was achieved by 48% of those on the 40 mg dose at week 16 and by 50% at week 46. For the 80-mg group, this rate rose from 52% to 79%. In the group that went from placebo to 80 mg, the ACR 50 rose from 13% with placebo to 73% with izokibep at week 46.

Resolution of enthesitis, measured by the Leeds Enthesitis Index, among those on the 40 mg dose, was achieved by 63% at week 16 and 83% at week 46, and among those on the 80 mg dose, 88% at week 16 and 89% at week 46. Those on placebo who switched to 80 mg of izokibep at week 16 had an 80% rate of enthesitis resolution at week 46.

Total resolution of skin involvement – 100% clearance of psoriasis based on the Psoriasis Area Severity Index (PASI) – was observed at 46 weeks in 50% of those on 40 mg, 71% of those on 80 mg, and 67% of those on 80 mg after week 16.

In its announcement, Acelyrin did not report withdrawal rates from the study after 16 weeks and through 46 weeks, although the statement said that izokibep “was generally well tolerated through 46 weeks, which is in line with previous trials of izokibep.” The most common adverse event was localized injection site reactions, with the majority graded mild to moderate in severity. They were generally the size of a quarter to half-dollar, and typically presented within the first few injections, after which they declined in incidence. In the trial, a case of vulvar cancer was determined to be potentially drug related, the company said.

Acelyrin is currently conducting a phase 2b/3 trial in PsA evaluating a range of doses, including significantly higher doses than in the phase 2 trial, that the company said “could potentially result in better ACR, PASI, and enthesitis resolution responses.”

The drug has been tested at doses up to 160 mg, in some cases for up to 3 years, in more than 400 patients with psoriasis, spondyloarthritis, noninfective uveitis, and hidradenitis suppurativa.

The full 46-week data from this trial will be presented at a future scientific meeting, according to the company.

The investigational interleukin-17A inhibitor izokibep showed higher response rates across a number of symptoms in adults with psoriatic arthritis (PsA) in an extension of its phase 2 trial out to 46 weeks, according to an announcement reporting some of the long-term data by the drug’s developer, Acelyrin.

Izokibep is an antibody mimetic designed to inhibit IL-17A that the company says has “high potency and the potential for robust tissue penetration due to its small molecular size, about one-tenth the size of a monoclonal antibody.”

“Patients want both rapid and meaningful improvement of their symptoms, as well as lasting – and ideally improving – resolution of disease over time. Building on the 16-week data for izokibep reported at EULAR and ACR [American College of Rheumatology] last year, the 46-week data now show not only continued but marked improvements over time in key areas of psoriatic arthritis including joint pain, skin psoriasis, and enthesitis,” Philip J. Mease, MD, director of rheumatology research at the Swedish Medical Center and clinical professor at the University of Washington, both in Seattle, and an investigator in the izokibep PsA program, said in the announcement.

The phase 2 trial tested two doses of izokibep – 40 mg and 80 mg – given by subcutaneous injection every 2 weeks – against placebo in 135 adult patients with active PsA. For inclusion in the trial, patients had to have at least three swollen and at least three tender joints and an inadequate response to prior therapy including NSAIDs, conventional synthetic disease-modifying antirheumatic drugs, or tumor necrosis factor inhibitors. At week 16, the placebo group transitioned to 80 mg izokibep every 2 weeks and the trial treatment period continued for up to 46 weeks.

The trial’s primary endpoint of a 50% or higher level of improvement in ACR response criteria (ACR 50) was achieved by 48% of those on the 40 mg dose at week 16 and by 50% at week 46. For the 80-mg group, this rate rose from 52% to 79%. In the group that went from placebo to 80 mg, the ACR 50 rose from 13% with placebo to 73% with izokibep at week 46.

Resolution of enthesitis, measured by the Leeds Enthesitis Index, among those on the 40 mg dose, was achieved by 63% at week 16 and 83% at week 46, and among those on the 80 mg dose, 88% at week 16 and 89% at week 46. Those on placebo who switched to 80 mg of izokibep at week 16 had an 80% rate of enthesitis resolution at week 46.

Total resolution of skin involvement – 100% clearance of psoriasis based on the Psoriasis Area Severity Index (PASI) – was observed at 46 weeks in 50% of those on 40 mg, 71% of those on 80 mg, and 67% of those on 80 mg after week 16.

In its announcement, Acelyrin did not report withdrawal rates from the study after 16 weeks and through 46 weeks, although the statement said that izokibep “was generally well tolerated through 46 weeks, which is in line with previous trials of izokibep.” The most common adverse event was localized injection site reactions, with the majority graded mild to moderate in severity. They were generally the size of a quarter to half-dollar, and typically presented within the first few injections, after which they declined in incidence. In the trial, a case of vulvar cancer was determined to be potentially drug related, the company said.

Acelyrin is currently conducting a phase 2b/3 trial in PsA evaluating a range of doses, including significantly higher doses than in the phase 2 trial, that the company said “could potentially result in better ACR, PASI, and enthesitis resolution responses.”

The drug has been tested at doses up to 160 mg, in some cases for up to 3 years, in more than 400 patients with psoriasis, spondyloarthritis, noninfective uveitis, and hidradenitis suppurativa.

The full 46-week data from this trial will be presented at a future scientific meeting, according to the company.

The investigational interleukin-17A inhibitor izokibep showed higher response rates across a number of symptoms in adults with psoriatic arthritis (PsA) in an extension of its phase 2 trial out to 46 weeks, according to an announcement reporting some of the long-term data by the drug’s developer, Acelyrin.

Izokibep is an antibody mimetic designed to inhibit IL-17A that the company says has “high potency and the potential for robust tissue penetration due to its small molecular size, about one-tenth the size of a monoclonal antibody.”

“Patients want both rapid and meaningful improvement of their symptoms, as well as lasting – and ideally improving – resolution of disease over time. Building on the 16-week data for izokibep reported at EULAR and ACR [American College of Rheumatology] last year, the 46-week data now show not only continued but marked improvements over time in key areas of psoriatic arthritis including joint pain, skin psoriasis, and enthesitis,” Philip J. Mease, MD, director of rheumatology research at the Swedish Medical Center and clinical professor at the University of Washington, both in Seattle, and an investigator in the izokibep PsA program, said in the announcement.

The phase 2 trial tested two doses of izokibep – 40 mg and 80 mg – given by subcutaneous injection every 2 weeks – against placebo in 135 adult patients with active PsA. For inclusion in the trial, patients had to have at least three swollen and at least three tender joints and an inadequate response to prior therapy including NSAIDs, conventional synthetic disease-modifying antirheumatic drugs, or tumor necrosis factor inhibitors. At week 16, the placebo group transitioned to 80 mg izokibep every 2 weeks and the trial treatment period continued for up to 46 weeks.

The trial’s primary endpoint of a 50% or higher level of improvement in ACR response criteria (ACR 50) was achieved by 48% of those on the 40 mg dose at week 16 and by 50% at week 46. For the 80-mg group, this rate rose from 52% to 79%. In the group that went from placebo to 80 mg, the ACR 50 rose from 13% with placebo to 73% with izokibep at week 46.

Resolution of enthesitis, measured by the Leeds Enthesitis Index, among those on the 40 mg dose, was achieved by 63% at week 16 and 83% at week 46, and among those on the 80 mg dose, 88% at week 16 and 89% at week 46. Those on placebo who switched to 80 mg of izokibep at week 16 had an 80% rate of enthesitis resolution at week 46.

Total resolution of skin involvement – 100% clearance of psoriasis based on the Psoriasis Area Severity Index (PASI) – was observed at 46 weeks in 50% of those on 40 mg, 71% of those on 80 mg, and 67% of those on 80 mg after week 16.

In its announcement, Acelyrin did not report withdrawal rates from the study after 16 weeks and through 46 weeks, although the statement said that izokibep “was generally well tolerated through 46 weeks, which is in line with previous trials of izokibep.” The most common adverse event was localized injection site reactions, with the majority graded mild to moderate in severity. They were generally the size of a quarter to half-dollar, and typically presented within the first few injections, after which they declined in incidence. In the trial, a case of vulvar cancer was determined to be potentially drug related, the company said.

Acelyrin is currently conducting a phase 2b/3 trial in PsA evaluating a range of doses, including significantly higher doses than in the phase 2 trial, that the company said “could potentially result in better ACR, PASI, and enthesitis resolution responses.”

The drug has been tested at doses up to 160 mg, in some cases for up to 3 years, in more than 400 patients with psoriasis, spondyloarthritis, noninfective uveitis, and hidradenitis suppurativa.

The full 46-week data from this trial will be presented at a future scientific meeting, according to the company.

The presence of antiphospholipid antibodies is associated with an increased risk for future cardiovascular events, according to a new study.

The findings point to possible new approaches to risk stratification and the potential for new therapeutic targets in heart disease.

“In this study of the general population, we found that two antiphospholipid antibodies were associated with an increased risk of having a serious cardiovascular event over a follow-up of 8 years,” coauthor Jason Knight, MD, University of Michigan, Ann Arbor, said in an interview.

“If confirmed in further studies, these findings could be used to identify a subgroup of patients who need more careful monitoring and more aggressive risk-factor modification, and if the increased risk linked to these antibodies is high enough, it may also justify preemptive treatments such as the anticoagulants that are routinely used in antiphospholipid syndrome,” Dr. Knight said.

“The long-term vision is that we may identify some people in the general population who would benefit from treating the immune system for the prevention and treatment of cardiovascular disease instead of, or in addition to, using typical cardiovascular medications,” he added.

The study was published online in JAMA Network Open.

Individuals with autoimmune and inflammatory diseases have a greater risk for cardiovascular events than expected based on traditional cardiovascular risk factors, with mechanisms proposed to explain this risk including inflammation-mediated disruption of vascular integrity and activation of platelets and coagulation pathways, the authors explained. However, the role of autoantibodies remains unclear.

They noted that antiphospholipid antibodies can activate endothelial cells, platelets, and neutrophils, and some patients with persistently circulating antiphospholipid antibodies can develop antiphospholipid syndrome – an acquired thromboinflammatory disease characterized by arterial, venous, and microvascular thrombotic events and obstetric complications.

Cross-sectional studies have shown that antiphospholipid antibodies are acutely present in up to 17.4% of patients with stroke or transient ischemic attack, and small cohort studies have suggested that such antibodies may be present in 1%-12% of seemingly healthy individuals. However, the impact of sex, race, and ethnicity on the prevalence of antiphospholipid antibodies and their association with atherosclerotic cardiovascular disease is not known.

The researchers conducted the current study to look at the association between antiphospholipid antibodies and future risk for atherosclerotic cardiovascular events.

They analyzed data from 2,427 participants in the population-based Dallas Heart Study who had no history of atherosclerotic cardiovascular disease or autoimmune diseases requiring immunosuppressive medications at the time of blood sampling at study entry in 2007-2009.

Eight different types of antiphospholipid antibodies were measured, and data on cardiovascular events over the next 8 years was recorded.

Results showed that 14.5% of the cohort tested positive for one of these antiphospholipid antibodies at the start of the study, with approximately one-third of those detected at a moderate or high titer.

The researchers also found that the IgA isotypes of two antiphospholipid antibodies – anticardiolipin and anti-beta-2 glycoprotein – were associated with future atherosclerotic cardiovascular events.

After adjustment for other known risk factors, individuals testing positive for the IgA isotype of anticardiolipin had an almost five times increased risk (hazard ratio, 4.92) of the primary endpoint (myocardial infarction, stroke, coronary revascularization, or cardiovascular death); while those testing positive for anti–beta₂-glycoprotein had an almost three times increased risk (HR, 2.91).

Furthermore, there was what appeared to be a dose effect. People with the highest levels of these antibodies also had the highest risk for cardiovascular events, with up to an almost 10-fold increased risk with the higher level of anticardiolipin. 

Dr. Knight said that more research into the IgA isotypes of these antiphospholipid antibodies is needed.

“Most of the mechanistic work in the antiphospholipid syndrome field has focused on IgG antiphospholipid antibodies. While we commonly find these IgA antibodies in patients with APS, the extent to which they contribute to disease has not been firmly established,” he said. “The fact that IgA was the primary hit in our unbiased screen suggests that there is more to the story and we need to better understand the implications of having these antibodies in circulation, and what specific problems they may be causing.”

Noting that antiphospholipid antibodies can form transiently after certain situations, such as infections, Dr. Knight said that further studies were needed with repeat blood testing to detect the chronic presence of the antibodies.

He added that information of venous thromboses was not available in this study and “perhaps some of the other antibodies might have stood out if we were able to analyze for different outcomes.”

This study was supported by a Pfizer Aspire Award. Dr. Knight reported receiving research funding and consulting fees from Jazz Pharmaceuticals outside the submitted work.

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

The presence of antiphospholipid antibodies is associated with an increased risk for future cardiovascular events, according to a new study.

The findings point to possible new approaches to risk stratification and the potential for new therapeutic targets in heart disease.

“In this study of the general population, we found that two antiphospholipid antibodies were associated with an increased risk of having a serious cardiovascular event over a follow-up of 8 years,” coauthor Jason Knight, MD, University of Michigan, Ann Arbor, said in an interview.

“If confirmed in further studies, these findings could be used to identify a subgroup of patients who need more careful monitoring and more aggressive risk-factor modification, and if the increased risk linked to these antibodies is high enough, it may also justify preemptive treatments such as the anticoagulants that are routinely used in antiphospholipid syndrome,” Dr. Knight said.

“The long-term vision is that we may identify some people in the general population who would benefit from treating the immune system for the prevention and treatment of cardiovascular disease instead of, or in addition to, using typical cardiovascular medications,” he added.

The study was published online in JAMA Network Open.

Individuals with autoimmune and inflammatory diseases have a greater risk for cardiovascular events than expected based on traditional cardiovascular risk factors, with mechanisms proposed to explain this risk including inflammation-mediated disruption of vascular integrity and activation of platelets and coagulation pathways, the authors explained. However, the role of autoantibodies remains unclear.

They noted that antiphospholipid antibodies can activate endothelial cells, platelets, and neutrophils, and some patients with persistently circulating antiphospholipid antibodies can develop antiphospholipid syndrome – an acquired thromboinflammatory disease characterized by arterial, venous, and microvascular thrombotic events and obstetric complications.

Cross-sectional studies have shown that antiphospholipid antibodies are acutely present in up to 17.4% of patients with stroke or transient ischemic attack, and small cohort studies have suggested that such antibodies may be present in 1%-12% of seemingly healthy individuals. However, the impact of sex, race, and ethnicity on the prevalence of antiphospholipid antibodies and their association with atherosclerotic cardiovascular disease is not known.

The researchers conducted the current study to look at the association between antiphospholipid antibodies and future risk for atherosclerotic cardiovascular events.

They analyzed data from 2,427 participants in the population-based Dallas Heart Study who had no history of atherosclerotic cardiovascular disease or autoimmune diseases requiring immunosuppressive medications at the time of blood sampling at study entry in 2007-2009.

Eight different types of antiphospholipid antibodies were measured, and data on cardiovascular events over the next 8 years was recorded.

Results showed that 14.5% of the cohort tested positive for one of these antiphospholipid antibodies at the start of the study, with approximately one-third of those detected at a moderate or high titer.

The researchers also found that the IgA isotypes of two antiphospholipid antibodies – anticardiolipin and anti-beta-2 glycoprotein – were associated with future atherosclerotic cardiovascular events.

After adjustment for other known risk factors, individuals testing positive for the IgA isotype of anticardiolipin had an almost five times increased risk (hazard ratio, 4.92) of the primary endpoint (myocardial infarction, stroke, coronary revascularization, or cardiovascular death); while those testing positive for anti–beta₂-glycoprotein had an almost three times increased risk (HR, 2.91).

Furthermore, there was what appeared to be a dose effect. People with the highest levels of these antibodies also had the highest risk for cardiovascular events, with up to an almost 10-fold increased risk with the higher level of anticardiolipin. 

Dr. Knight said that more research into the IgA isotypes of these antiphospholipid antibodies is needed.

“Most of the mechanistic work in the antiphospholipid syndrome field has focused on IgG antiphospholipid antibodies. While we commonly find these IgA antibodies in patients with APS, the extent to which they contribute to disease has not been firmly established,” he said. “The fact that IgA was the primary hit in our unbiased screen suggests that there is more to the story and we need to better understand the implications of having these antibodies in circulation, and what specific problems they may be causing.”

Noting that antiphospholipid antibodies can form transiently after certain situations, such as infections, Dr. Knight said that further studies were needed with repeat blood testing to detect the chronic presence of the antibodies.

He added that information of venous thromboses was not available in this study and “perhaps some of the other antibodies might have stood out if we were able to analyze for different outcomes.”

This study was supported by a Pfizer Aspire Award. Dr. Knight reported receiving research funding and consulting fees from Jazz Pharmaceuticals outside the submitted work.

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

The presence of antiphospholipid antibodies is associated with an increased risk for future cardiovascular events, according to a new study.

The findings point to possible new approaches to risk stratification and the potential for new therapeutic targets in heart disease.

“In this study of the general population, we found that two antiphospholipid antibodies were associated with an increased risk of having a serious cardiovascular event over a follow-up of 8 years,” coauthor Jason Knight, MD, University of Michigan, Ann Arbor, said in an interview.

“If confirmed in further studies, these findings could be used to identify a subgroup of patients who need more careful monitoring and more aggressive risk-factor modification, and if the increased risk linked to these antibodies is high enough, it may also justify preemptive treatments such as the anticoagulants that are routinely used in antiphospholipid syndrome,” Dr. Knight said.

“The long-term vision is that we may identify some people in the general population who would benefit from treating the immune system for the prevention and treatment of cardiovascular disease instead of, or in addition to, using typical cardiovascular medications,” he added.

The study was published online in JAMA Network Open.

Individuals with autoimmune and inflammatory diseases have a greater risk for cardiovascular events than expected based on traditional cardiovascular risk factors, with mechanisms proposed to explain this risk including inflammation-mediated disruption of vascular integrity and activation of platelets and coagulation pathways, the authors explained. However, the role of autoantibodies remains unclear.

They noted that antiphospholipid antibodies can activate endothelial cells, platelets, and neutrophils, and some patients with persistently circulating antiphospholipid antibodies can develop antiphospholipid syndrome – an acquired thromboinflammatory disease characterized by arterial, venous, and microvascular thrombotic events and obstetric complications.

Cross-sectional studies have shown that antiphospholipid antibodies are acutely present in up to 17.4% of patients with stroke or transient ischemic attack, and small cohort studies have suggested that such antibodies may be present in 1%-12% of seemingly healthy individuals. However, the impact of sex, race, and ethnicity on the prevalence of antiphospholipid antibodies and their association with atherosclerotic cardiovascular disease is not known.

The researchers conducted the current study to look at the association between antiphospholipid antibodies and future risk for atherosclerotic cardiovascular events.

They analyzed data from 2,427 participants in the population-based Dallas Heart Study who had no history of atherosclerotic cardiovascular disease or autoimmune diseases requiring immunosuppressive medications at the time of blood sampling at study entry in 2007-2009.

Eight different types of antiphospholipid antibodies were measured, and data on cardiovascular events over the next 8 years was recorded.

Results showed that 14.5% of the cohort tested positive for one of these antiphospholipid antibodies at the start of the study, with approximately one-third of those detected at a moderate or high titer.

The researchers also found that the IgA isotypes of two antiphospholipid antibodies – anticardiolipin and anti-beta-2 glycoprotein – were associated with future atherosclerotic cardiovascular events.

After adjustment for other known risk factors, individuals testing positive for the IgA isotype of anticardiolipin had an almost five times increased risk (hazard ratio, 4.92) of the primary endpoint (myocardial infarction, stroke, coronary revascularization, or cardiovascular death); while those testing positive for anti–beta₂-glycoprotein had an almost three times increased risk (HR, 2.91).

Furthermore, there was what appeared to be a dose effect. People with the highest levels of these antibodies also had the highest risk for cardiovascular events, with up to an almost 10-fold increased risk with the higher level of anticardiolipin. 

Dr. Knight said that more research into the IgA isotypes of these antiphospholipid antibodies is needed.

“Most of the mechanistic work in the antiphospholipid syndrome field has focused on IgG antiphospholipid antibodies. While we commonly find these IgA antibodies in patients with APS, the extent to which they contribute to disease has not been firmly established,” he said. “The fact that IgA was the primary hit in our unbiased screen suggests that there is more to the story and we need to better understand the implications of having these antibodies in circulation, and what specific problems they may be causing.”

Noting that antiphospholipid antibodies can form transiently after certain situations, such as infections, Dr. Knight said that further studies were needed with repeat blood testing to detect the chronic presence of the antibodies.

He added that information of venous thromboses was not available in this study and “perhaps some of the other antibodies might have stood out if we were able to analyze for different outcomes.”

This study was supported by a Pfizer Aspire Award. Dr. Knight reported receiving research funding and consulting fees from Jazz Pharmaceuticals outside the submitted work.

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

NEW ORLEANS – The sociodemographic characteristics of Black and Hispanic children with systemic lupus erythematosus (SLE) appear to play a strong role in influencing the severity of disease in these patients, according to two studies presented at the Pediatric Rheumatology Symposium.

One study showed an association between multiple determinants of health and disease severity among children seen in a large Texas city, and a separate descriptive cross-sectional cohort study of predominantly Black children at two centers in Mississippi and Alabama reinforced the finding of greater severity of disease and social hardships among this racial group.

The findings from both studies supplement existing evidence that the prevalence of childhood-onset SLE is greater among Black and Hispanic children.

“Several demographic and social determinants of health parameters influenced disease severity at levels that reached statistical significance, including insurance status, race/ethnicity, referral source, PCP [primary care provider] availability, primary language, and transportation needs,” Emily Beil, MD, a pediatric rheumatologist at Texas Children’s Hospital in Houston, told attendees at the conference, which was sponsored by the American College of Rheumatology. Her team’s goal, she said, was to “better understand our patient population and social disparities that contribute to disease severity.”

Dr. Beil and her colleagues conducted a retrospective review of 136 children who had been diagnosed with childhood-onset SLE between January 2018 and May 2022 at Texas Children’s Hospital. Only children who were younger than 18 years at the time of diagnosis at Texas Children’s were included. The analysis considered demographics, clinical characteristics, insurance status, social work consultation, access to a primary care provider, transportation needs, primary language, and other parameters related to social determinants of health.

The average age of the patients was 13 years, and most were girls (82%). Just over half were Hispanic (53%), and just over a quarter were Black (26%). Half had Medicaid or participated in the Children’s Health Insurance Program (CHIP), and 1 in 10 were uninsured (10%). Half the diagnoses were made during an inpatient admission; 36% were made on the floor, and 14% were made in the intensive care unit (ICU).

The average Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 12.5, and 48.5% of patients had severe disease, indicated by a score of at least 12. Only two in three children were documented as having a primary care physician (66%), and 32% preferred a language other than English. Most of the children (80%) had a social work consult.

Black and biracial children had higher SLEDAI scores at presentation. Non-Hispanic White children were less likely to have a social work consult, compared with other racial/ethnic groups (P = .01 for both). Central nervous system involvement was most prevalent among Black patients (P = .004). Cyclophosphamide was used most often for Black and biracial patients.

Uninsured patients were most likely to be diagnosed on an inpatient floor. The highest proportion of ICU admissions was among patients insured by Medicaid (P = .034). Average SLEDAI scores were highest among uninsured patients, followed by Medicaid patients. More than half of the patients who did not have insurance lacked access to a regular primary care provider, compared with 12% of Medicaid patients and 7% of privately insured patients (P = .001). All the uninsured patients had transportation needs, which was a significantly higher rate than among those with Medicaid (13%) or private insurance (15%) (P = .001). The highest percentage of social work consults was among patients who were insured by Medicaid or were without insurance (P = .001).
 

Salient demographics and clinical features

In the second presentation, Anita Dhanrajani, MD, assistant professor of pediatrics at the University of Mississippi Medical Center in Jackson, began by noting that Alabama and Mississippi are ranked in the top 10 states for the highest poverty rate: Mississippi is No. 1, and Alabama is No. 7. Further, 40% of children in Mississippi and 29% of children in Alabama are of African American ancestry, she said.

“So, we know that this population that we’re dealing with has several high-risk factors that can lead them to have poor outcomes, and yet, we haven’t really ever characterized their clinical features or their social demographic features,” Dr. Dhanrajani told attendees. “My hope is that with this very miniscule first step, we’re able to move towards solutions to decrease health care disparities in this population.”

She presented findings regarding the first of three aims in the study, which was to describe the baseline clinical, demographic, and socioeconomic profiles of childhood lupus patients at the two centers. The two other aims were to examine genetic factors potentially linked to poor outcomes in the cohort and to assess the mental health status of the population.

The study relied on a retrospective chart review for the 17 patients at the University of Mississippi Medical Center and on Childhood Arthritis and Rheumatology Research Alliance registry data for the 19 patients at the University of Alabama at Birmingham. Most of the patients (86%) were female, Black (78%), and insured by Medicaid (64%). The average age at diagnosis was 13 years. Most (83%) also lived in a ZIP code that met the criteria for a medium-high or high Social Vulnerability Index. The children had to travel an average 75 miles to see a rheumatologist, compared with the national average of 43 miles.

At diagnosis, their average Systemic Lupus International Collaborating Clinics (SLICC) score was 8.8, their average American College of Rheumatology score was 5.2, and their average SLEDAI score was 12.1 – the latter was substantially higher than the average 3.1 score in a multiethnic Canadian cohort (the 1000 Canadian Faces of Lupus Study) with 10% Black children (P < .00001). The SLEDAI score dropped to 6.8 at 6 months and to 4 at 1 year. Nearly half (47%) had a SLICC Damage Index (SDI) greater than 0, and one-third had an SDI of 2 or greater, compared with 16% and 7%, respectively, reported in other recent studies (P < .0001 for both).

“These disparities are very difficult to investigate in terms of causal relationships and [are] likely to be very modifiable,” Coziana Ciurtin, MD, PhD, associate professor of rheumatology at University College London, told this news organization. “I think the socioeconomic status, the level of education, poverty, [type of] medical insurance, and probably genetic variants are all underpinning the presentation, damage, or disease activity being very high, and also organ involvement,” such as the greater CNS involvement seen in non-White patients.

Being mindful of these risk profiles can help doctors in asking about patients’ support at home and their families’ education, beliefs, and cultural practices, Dr. Ciurtin added. “Helping them to engage and be involved in decision-making is probably the most important” aspect of learning this information about families, she said.

Collecting this information should not be the sole responsibility of the physician, added Eve Smith, PhD, MBCHB, an academic clinical lecturer at the University of Liverpool, England, who attended the presentations. Dr. Smith noted a discussion in a work group during the previous day of the conference concerning questionnaires for screening patients regarding the need for social services and for identifying areas in which patients and their families were having difficulties.

“Obviously, if you’re going to do that, you have to have access to someone who can actually help to deal with that. Some hospitals have patient navigators that can help, for example, with a food security issue to highlight resources within the community, so it’s not all on the doctor,” Dr. Smith said. “To really make a difference in this area, it can’t just be down to the doctor. There needs to be social care, there needs to be community-based interventions and things to do about it. Doctors can help identify these patients, or maybe somebody in the [medical] team can help with that, but there needs to be an intervention. Otherwise, you’re left with this problem without a solution that you can’t do anything about.”

The researchers did not note any external funding for either study. Dr. Beil, Dr. Dhanrajani, Dr. Smith, and Dr. Ciurtin reported no relevant financial relationships.

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

NEW ORLEANS – The sociodemographic characteristics of Black and Hispanic children with systemic lupus erythematosus (SLE) appear to play a strong role in influencing the severity of disease in these patients, according to two studies presented at the Pediatric Rheumatology Symposium.

One study showed an association between multiple determinants of health and disease severity among children seen in a large Texas city, and a separate descriptive cross-sectional cohort study of predominantly Black children at two centers in Mississippi and Alabama reinforced the finding of greater severity of disease and social hardships among this racial group.

The findings from both studies supplement existing evidence that the prevalence of childhood-onset SLE is greater among Black and Hispanic children.

“Several demographic and social determinants of health parameters influenced disease severity at levels that reached statistical significance, including insurance status, race/ethnicity, referral source, PCP [primary care provider] availability, primary language, and transportation needs,” Emily Beil, MD, a pediatric rheumatologist at Texas Children’s Hospital in Houston, told attendees at the conference, which was sponsored by the American College of Rheumatology. Her team’s goal, she said, was to “better understand our patient population and social disparities that contribute to disease severity.”

Dr. Beil and her colleagues conducted a retrospective review of 136 children who had been diagnosed with childhood-onset SLE between January 2018 and May 2022 at Texas Children’s Hospital. Only children who were younger than 18 years at the time of diagnosis at Texas Children’s were included. The analysis considered demographics, clinical characteristics, insurance status, social work consultation, access to a primary care provider, transportation needs, primary language, and other parameters related to social determinants of health.

The average age of the patients was 13 years, and most were girls (82%). Just over half were Hispanic (53%), and just over a quarter were Black (26%). Half had Medicaid or participated in the Children’s Health Insurance Program (CHIP), and 1 in 10 were uninsured (10%). Half the diagnoses were made during an inpatient admission; 36% were made on the floor, and 14% were made in the intensive care unit (ICU).

The average Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 12.5, and 48.5% of patients had severe disease, indicated by a score of at least 12. Only two in three children were documented as having a primary care physician (66%), and 32% preferred a language other than English. Most of the children (80%) had a social work consult.

Black and biracial children had higher SLEDAI scores at presentation. Non-Hispanic White children were less likely to have a social work consult, compared with other racial/ethnic groups (P = .01 for both). Central nervous system involvement was most prevalent among Black patients (P = .004). Cyclophosphamide was used most often for Black and biracial patients.

Uninsured patients were most likely to be diagnosed on an inpatient floor. The highest proportion of ICU admissions was among patients insured by Medicaid (P = .034). Average SLEDAI scores were highest among uninsured patients, followed by Medicaid patients. More than half of the patients who did not have insurance lacked access to a regular primary care provider, compared with 12% of Medicaid patients and 7% of privately insured patients (P = .001). All the uninsured patients had transportation needs, which was a significantly higher rate than among those with Medicaid (13%) or private insurance (15%) (P = .001). The highest percentage of social work consults was among patients who were insured by Medicaid or were without insurance (P = .001).
 

Salient demographics and clinical features

In the second presentation, Anita Dhanrajani, MD, assistant professor of pediatrics at the University of Mississippi Medical Center in Jackson, began by noting that Alabama and Mississippi are ranked in the top 10 states for the highest poverty rate: Mississippi is No. 1, and Alabama is No. 7. Further, 40% of children in Mississippi and 29% of children in Alabama are of African American ancestry, she said.

“So, we know that this population that we’re dealing with has several high-risk factors that can lead them to have poor outcomes, and yet, we haven’t really ever characterized their clinical features or their social demographic features,” Dr. Dhanrajani told attendees. “My hope is that with this very miniscule first step, we’re able to move towards solutions to decrease health care disparities in this population.”

She presented findings regarding the first of three aims in the study, which was to describe the baseline clinical, demographic, and socioeconomic profiles of childhood lupus patients at the two centers. The two other aims were to examine genetic factors potentially linked to poor outcomes in the cohort and to assess the mental health status of the population.

The study relied on a retrospective chart review for the 17 patients at the University of Mississippi Medical Center and on Childhood Arthritis and Rheumatology Research Alliance registry data for the 19 patients at the University of Alabama at Birmingham. Most of the patients (86%) were female, Black (78%), and insured by Medicaid (64%). The average age at diagnosis was 13 years. Most (83%) also lived in a ZIP code that met the criteria for a medium-high or high Social Vulnerability Index. The children had to travel an average 75 miles to see a rheumatologist, compared with the national average of 43 miles.

At diagnosis, their average Systemic Lupus International Collaborating Clinics (SLICC) score was 8.8, their average American College of Rheumatology score was 5.2, and their average SLEDAI score was 12.1 – the latter was substantially higher than the average 3.1 score in a multiethnic Canadian cohort (the 1000 Canadian Faces of Lupus Study) with 10% Black children (P < .00001). The SLEDAI score dropped to 6.8 at 6 months and to 4 at 1 year. Nearly half (47%) had a SLICC Damage Index (SDI) greater than 0, and one-third had an SDI of 2 or greater, compared with 16% and 7%, respectively, reported in other recent studies (P < .0001 for both).

“These disparities are very difficult to investigate in terms of causal relationships and [are] likely to be very modifiable,” Coziana Ciurtin, MD, PhD, associate professor of rheumatology at University College London, told this news organization. “I think the socioeconomic status, the level of education, poverty, [type of] medical insurance, and probably genetic variants are all underpinning the presentation, damage, or disease activity being very high, and also organ involvement,” such as the greater CNS involvement seen in non-White patients.

Being mindful of these risk profiles can help doctors in asking about patients’ support at home and their families’ education, beliefs, and cultural practices, Dr. Ciurtin added. “Helping them to engage and be involved in decision-making is probably the most important” aspect of learning this information about families, she said.

Collecting this information should not be the sole responsibility of the physician, added Eve Smith, PhD, MBCHB, an academic clinical lecturer at the University of Liverpool, England, who attended the presentations. Dr. Smith noted a discussion in a work group during the previous day of the conference concerning questionnaires for screening patients regarding the need for social services and for identifying areas in which patients and their families were having difficulties.

“Obviously, if you’re going to do that, you have to have access to someone who can actually help to deal with that. Some hospitals have patient navigators that can help, for example, with a food security issue to highlight resources within the community, so it’s not all on the doctor,” Dr. Smith said. “To really make a difference in this area, it can’t just be down to the doctor. There needs to be social care, there needs to be community-based interventions and things to do about it. Doctors can help identify these patients, or maybe somebody in the [medical] team can help with that, but there needs to be an intervention. Otherwise, you’re left with this problem without a solution that you can’t do anything about.”

The researchers did not note any external funding for either study. Dr. Beil, Dr. Dhanrajani, Dr. Smith, and Dr. Ciurtin reported no relevant financial relationships.

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

NEW ORLEANS – The sociodemographic characteristics of Black and Hispanic children with systemic lupus erythematosus (SLE) appear to play a strong role in influencing the severity of disease in these patients, according to two studies presented at the Pediatric Rheumatology Symposium.

One study showed an association between multiple determinants of health and disease severity among children seen in a large Texas city, and a separate descriptive cross-sectional cohort study of predominantly Black children at two centers in Mississippi and Alabama reinforced the finding of greater severity of disease and social hardships among this racial group.

The findings from both studies supplement existing evidence that the prevalence of childhood-onset SLE is greater among Black and Hispanic children.

“Several demographic and social determinants of health parameters influenced disease severity at levels that reached statistical significance, including insurance status, race/ethnicity, referral source, PCP [primary care provider] availability, primary language, and transportation needs,” Emily Beil, MD, a pediatric rheumatologist at Texas Children’s Hospital in Houston, told attendees at the conference, which was sponsored by the American College of Rheumatology. Her team’s goal, she said, was to “better understand our patient population and social disparities that contribute to disease severity.”

Dr. Beil and her colleagues conducted a retrospective review of 136 children who had been diagnosed with childhood-onset SLE between January 2018 and May 2022 at Texas Children’s Hospital. Only children who were younger than 18 years at the time of diagnosis at Texas Children’s were included. The analysis considered demographics, clinical characteristics, insurance status, social work consultation, access to a primary care provider, transportation needs, primary language, and other parameters related to social determinants of health.

The average age of the patients was 13 years, and most were girls (82%). Just over half were Hispanic (53%), and just over a quarter were Black (26%). Half had Medicaid or participated in the Children’s Health Insurance Program (CHIP), and 1 in 10 were uninsured (10%). Half the diagnoses were made during an inpatient admission; 36% were made on the floor, and 14% were made in the intensive care unit (ICU).

The average Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 12.5, and 48.5% of patients had severe disease, indicated by a score of at least 12. Only two in three children were documented as having a primary care physician (66%), and 32% preferred a language other than English. Most of the children (80%) had a social work consult.

Black and biracial children had higher SLEDAI scores at presentation. Non-Hispanic White children were less likely to have a social work consult, compared with other racial/ethnic groups (P = .01 for both). Central nervous system involvement was most prevalent among Black patients (P = .004). Cyclophosphamide was used most often for Black and biracial patients.

Uninsured patients were most likely to be diagnosed on an inpatient floor. The highest proportion of ICU admissions was among patients insured by Medicaid (P = .034). Average SLEDAI scores were highest among uninsured patients, followed by Medicaid patients. More than half of the patients who did not have insurance lacked access to a regular primary care provider, compared with 12% of Medicaid patients and 7% of privately insured patients (P = .001). All the uninsured patients had transportation needs, which was a significantly higher rate than among those with Medicaid (13%) or private insurance (15%) (P = .001). The highest percentage of social work consults was among patients who were insured by Medicaid or were without insurance (P = .001).
 

Salient demographics and clinical features

In the second presentation, Anita Dhanrajani, MD, assistant professor of pediatrics at the University of Mississippi Medical Center in Jackson, began by noting that Alabama and Mississippi are ranked in the top 10 states for the highest poverty rate: Mississippi is No. 1, and Alabama is No. 7. Further, 40% of children in Mississippi and 29% of children in Alabama are of African American ancestry, she said.

“So, we know that this population that we’re dealing with has several high-risk factors that can lead them to have poor outcomes, and yet, we haven’t really ever characterized their clinical features or their social demographic features,” Dr. Dhanrajani told attendees. “My hope is that with this very miniscule first step, we’re able to move towards solutions to decrease health care disparities in this population.”

She presented findings regarding the first of three aims in the study, which was to describe the baseline clinical, demographic, and socioeconomic profiles of childhood lupus patients at the two centers. The two other aims were to examine genetic factors potentially linked to poor outcomes in the cohort and to assess the mental health status of the population.

The study relied on a retrospective chart review for the 17 patients at the University of Mississippi Medical Center and on Childhood Arthritis and Rheumatology Research Alliance registry data for the 19 patients at the University of Alabama at Birmingham. Most of the patients (86%) were female, Black (78%), and insured by Medicaid (64%). The average age at diagnosis was 13 years. Most (83%) also lived in a ZIP code that met the criteria for a medium-high or high Social Vulnerability Index. The children had to travel an average 75 miles to see a rheumatologist, compared with the national average of 43 miles.

At diagnosis, their average Systemic Lupus International Collaborating Clinics (SLICC) score was 8.8, their average American College of Rheumatology score was 5.2, and their average SLEDAI score was 12.1 – the latter was substantially higher than the average 3.1 score in a multiethnic Canadian cohort (the 1000 Canadian Faces of Lupus Study) with 10% Black children (P < .00001). The SLEDAI score dropped to 6.8 at 6 months and to 4 at 1 year. Nearly half (47%) had a SLICC Damage Index (SDI) greater than 0, and one-third had an SDI of 2 or greater, compared with 16% and 7%, respectively, reported in other recent studies (P < .0001 for both).

“These disparities are very difficult to investigate in terms of causal relationships and [are] likely to be very modifiable,” Coziana Ciurtin, MD, PhD, associate professor of rheumatology at University College London, told this news organization. “I think the socioeconomic status, the level of education, poverty, [type of] medical insurance, and probably genetic variants are all underpinning the presentation, damage, or disease activity being very high, and also organ involvement,” such as the greater CNS involvement seen in non-White patients.

Being mindful of these risk profiles can help doctors in asking about patients’ support at home and their families’ education, beliefs, and cultural practices, Dr. Ciurtin added. “Helping them to engage and be involved in decision-making is probably the most important” aspect of learning this information about families, she said.

Collecting this information should not be the sole responsibility of the physician, added Eve Smith, PhD, MBCHB, an academic clinical lecturer at the University of Liverpool, England, who attended the presentations. Dr. Smith noted a discussion in a work group during the previous day of the conference concerning questionnaires for screening patients regarding the need for social services and for identifying areas in which patients and their families were having difficulties.

“Obviously, if you’re going to do that, you have to have access to someone who can actually help to deal with that. Some hospitals have patient navigators that can help, for example, with a food security issue to highlight resources within the community, so it’s not all on the doctor,” Dr. Smith said. “To really make a difference in this area, it can’t just be down to the doctor. There needs to be social care, there needs to be community-based interventions and things to do about it. Doctors can help identify these patients, or maybe somebody in the [medical] team can help with that, but there needs to be an intervention. Otherwise, you’re left with this problem without a solution that you can’t do anything about.”

The researchers did not note any external funding for either study. Dr. Beil, Dr. Dhanrajani, Dr. Smith, and Dr. Ciurtin reported no relevant financial relationships.

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

DENVER – Metabolic syndrome in both early and mid-adulthood is associated with symptoms of knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress.

©pixologicstudio/Thinkstock

Data at both time points included fasting blood biochemistry, waist circumference, and blood pressure measures. The criteria for metabolic syndrome requires presence of central obesity (a waist circumference of at least 94 cm in males or 80 cm in females) and two of the following four factors:

• Raised triglycerides (at least 150 mg/dL) or specific treatment for this lipid abnormality.
• Reduced HDL cholesterol (below 40 mg/dL in males and below 50 mg/dL in females) or treatment for this.
• Raised blood pressure (at least 130 mm Hg systolic or at least 85 mm Hg diastolic) or treatment of previously diagnosed hypertension.
• Raised fasting blood glucose (at least 100 mg/dL) or previously diagnosed type 2 diabetes.

The researchers grouped the participants on the basis of having no metabolic syndrome at either life stage, having metabolic syndrome in young adulthood but not at follow-up (improved), having developed metabolic syndrome at follow-up (incident), and having metabolic syndrome at both time points (persistent). Most of the participants did not have the metabolic syndrome at either time point (85%), whereas 2% improved in mid-adulthood, 9% developed incident metabolic syndrome in mid-adulthood, and 4% had persistent metabolic syndrome.

At follow-up, 43% of the participants reported pain on the WOMAC, and the average WOMAC score was 10. Prevalence of metabolic syndrome increased from 8% in young adulthood to 13% in mid-adulthood, with an increase in abdominal obesity prevalence from 29% to 47%. Metabolic syndrome at any time point – whether improved later, developed later, or persistent – was associated with more knee symptoms, compared with no metabolic syndrome.

Presence of metabolic syndrome in mid-adulthood was associated with knee symptoms from the total WOMAC score (ratio of means, 1.33; P < .001) after adjustment for age, sex, and body mass index (BMI). Metabolic syndrome was also independently associated in mid-adulthood with knee pain (RoM, 1.29; P < .001) and poor function (RoM, 1.37; P < .001).

Those who developed incident metabolic syndrome in mid-adulthood had the greatest association with overall knee symptoms (RoM, 1.56; P < .001) and with knee pain (RoM, 1.52; P < .001). Although improved and persistent metabolic syndrome were both significantly associated with total WOMAC score, neither was significantly associated with knee pain after adjustment for age, sex, and BMI.

The three individual metabolic criteria independently associated with overall WOMAC score were abdominal obesity (RoM, 1.09), hypertension (RoM, 1.44), and low HDL (RoM, 1.17; P < .001 for all).

Leigh F. Callahan, PhD, a professor of medicine and associate director of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, said in an interview that this topic is especially important because there’s so little understanding of the role of comorbid conditions and osteoarthritis.

“There were some key things that I thought were wonderful about this study – the longitudinal nature and the fact that they had collected metabolic syndrome [criteria] at multiple time points and were able to look at persistent versus incident metabolic syndrome,” Dr. Callahan said. “We frequently don’t have that kind of trajectory.”

Jaqueline Lourdes Rios, PhD, an assistant professor of orthopedics at University Medical Center Utrecht (Netherlands), said in an interview that the study raised questions about whether treating metabolic syndrome could help prevent the progression of osteoarthritis to some extent. “Although, if you already have damage in your cartilage, and if you have a lot of inflammation that’s local, it might be a bit trickier than just treating metabolic syndrome,” Dr. Lourdes Rios added. “Then, it might help, it might not.” Either way, she said, it’s certainly worthwhile for physicians to spend time discussing interventions to address metabolic syndrome “because you treat the patient, not a knee.”

Dr. Ding, Dr. Lourdes Rios, and Dr. Callahan had no relevant financial relationships to disclose. The researchers did not note any external funding.

DENVER – Metabolic syndrome in both early and mid-adulthood is associated with symptoms of knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress.

©pixologicstudio/Thinkstock

Data at both time points included fasting blood biochemistry, waist circumference, and blood pressure measures. The criteria for metabolic syndrome requires presence of central obesity (a waist circumference of at least 94 cm in males or 80 cm in females) and two of the following four factors:

• Raised triglycerides (at least 150 mg/dL) or specific treatment for this lipid abnormality.
• Reduced HDL cholesterol (below 40 mg/dL in males and below 50 mg/dL in females) or treatment for this.
• Raised blood pressure (at least 130 mm Hg systolic or at least 85 mm Hg diastolic) or treatment of previously diagnosed hypertension.
• Raised fasting blood glucose (at least 100 mg/dL) or previously diagnosed type 2 diabetes.

The researchers grouped the participants on the basis of having no metabolic syndrome at either life stage, having metabolic syndrome in young adulthood but not at follow-up (improved), having developed metabolic syndrome at follow-up (incident), and having metabolic syndrome at both time points (persistent). Most of the participants did not have the metabolic syndrome at either time point (85%), whereas 2% improved in mid-adulthood, 9% developed incident metabolic syndrome in mid-adulthood, and 4% had persistent metabolic syndrome.

At follow-up, 43% of the participants reported pain on the WOMAC, and the average WOMAC score was 10. Prevalence of metabolic syndrome increased from 8% in young adulthood to 13% in mid-adulthood, with an increase in abdominal obesity prevalence from 29% to 47%. Metabolic syndrome at any time point – whether improved later, developed later, or persistent – was associated with more knee symptoms, compared with no metabolic syndrome.

Presence of metabolic syndrome in mid-adulthood was associated with knee symptoms from the total WOMAC score (ratio of means, 1.33; P < .001) after adjustment for age, sex, and body mass index (BMI). Metabolic syndrome was also independently associated in mid-adulthood with knee pain (RoM, 1.29; P < .001) and poor function (RoM, 1.37; P < .001).

Those who developed incident metabolic syndrome in mid-adulthood had the greatest association with overall knee symptoms (RoM, 1.56; P < .001) and with knee pain (RoM, 1.52; P < .001). Although improved and persistent metabolic syndrome were both significantly associated with total WOMAC score, neither was significantly associated with knee pain after adjustment for age, sex, and BMI.

The three individual metabolic criteria independently associated with overall WOMAC score were abdominal obesity (RoM, 1.09), hypertension (RoM, 1.44), and low HDL (RoM, 1.17; P < .001 for all).

Leigh F. Callahan, PhD, a professor of medicine and associate director of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, said in an interview that this topic is especially important because there’s so little understanding of the role of comorbid conditions and osteoarthritis.

“There were some key things that I thought were wonderful about this study – the longitudinal nature and the fact that they had collected metabolic syndrome [criteria] at multiple time points and were able to look at persistent versus incident metabolic syndrome,” Dr. Callahan said. “We frequently don’t have that kind of trajectory.”

Jaqueline Lourdes Rios, PhD, an assistant professor of orthopedics at University Medical Center Utrecht (Netherlands), said in an interview that the study raised questions about whether treating metabolic syndrome could help prevent the progression of osteoarthritis to some extent. “Although, if you already have damage in your cartilage, and if you have a lot of inflammation that’s local, it might be a bit trickier than just treating metabolic syndrome,” Dr. Lourdes Rios added. “Then, it might help, it might not.” Either way, she said, it’s certainly worthwhile for physicians to spend time discussing interventions to address metabolic syndrome “because you treat the patient, not a knee.”

Dr. Ding, Dr. Lourdes Rios, and Dr. Callahan had no relevant financial relationships to disclose. The researchers did not note any external funding.

DENVER – Metabolic syndrome in both early and mid-adulthood is associated with symptoms of knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress.

©pixologicstudio/Thinkstock

Data at both time points included fasting blood biochemistry, waist circumference, and blood pressure measures. The criteria for metabolic syndrome requires presence of central obesity (a waist circumference of at least 94 cm in males or 80 cm in females) and two of the following four factors:

• Raised triglycerides (at least 150 mg/dL) or specific treatment for this lipid abnormality.
• Reduced HDL cholesterol (below 40 mg/dL in males and below 50 mg/dL in females) or treatment for this.
• Raised blood pressure (at least 130 mm Hg systolic or at least 85 mm Hg diastolic) or treatment of previously diagnosed hypertension.
• Raised fasting blood glucose (at least 100 mg/dL) or previously diagnosed type 2 diabetes.

The researchers grouped the participants on the basis of having no metabolic syndrome at either life stage, having metabolic syndrome in young adulthood but not at follow-up (improved), having developed metabolic syndrome at follow-up (incident), and having metabolic syndrome at both time points (persistent). Most of the participants did not have the metabolic syndrome at either time point (85%), whereas 2% improved in mid-adulthood, 9% developed incident metabolic syndrome in mid-adulthood, and 4% had persistent metabolic syndrome.

At follow-up, 43% of the participants reported pain on the WOMAC, and the average WOMAC score was 10. Prevalence of metabolic syndrome increased from 8% in young adulthood to 13% in mid-adulthood, with an increase in abdominal obesity prevalence from 29% to 47%. Metabolic syndrome at any time point – whether improved later, developed later, or persistent – was associated with more knee symptoms, compared with no metabolic syndrome.

Presence of metabolic syndrome in mid-adulthood was associated with knee symptoms from the total WOMAC score (ratio of means, 1.33; P < .001) after adjustment for age, sex, and body mass index (BMI). Metabolic syndrome was also independently associated in mid-adulthood with knee pain (RoM, 1.29; P < .001) and poor function (RoM, 1.37; P < .001).

Those who developed incident metabolic syndrome in mid-adulthood had the greatest association with overall knee symptoms (RoM, 1.56; P < .001) and with knee pain (RoM, 1.52; P < .001). Although improved and persistent metabolic syndrome were both significantly associated with total WOMAC score, neither was significantly associated with knee pain after adjustment for age, sex, and BMI.

The three individual metabolic criteria independently associated with overall WOMAC score were abdominal obesity (RoM, 1.09), hypertension (RoM, 1.44), and low HDL (RoM, 1.17; P < .001 for all).

Leigh F. Callahan, PhD, a professor of medicine and associate director of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, said in an interview that this topic is especially important because there’s so little understanding of the role of comorbid conditions and osteoarthritis.

“There were some key things that I thought were wonderful about this study – the longitudinal nature and the fact that they had collected metabolic syndrome [criteria] at multiple time points and were able to look at persistent versus incident metabolic syndrome,” Dr. Callahan said. “We frequently don’t have that kind of trajectory.”

Jaqueline Lourdes Rios, PhD, an assistant professor of orthopedics at University Medical Center Utrecht (Netherlands), said in an interview that the study raised questions about whether treating metabolic syndrome could help prevent the progression of osteoarthritis to some extent. “Although, if you already have damage in your cartilage, and if you have a lot of inflammation that’s local, it might be a bit trickier than just treating metabolic syndrome,” Dr. Lourdes Rios added. “Then, it might help, it might not.” Either way, she said, it’s certainly worthwhile for physicians to spend time discussing interventions to address metabolic syndrome “because you treat the patient, not a knee.”

Dr. Ding, Dr. Lourdes Rios, and Dr. Callahan had no relevant financial relationships to disclose. The researchers did not note any external funding.

Clinical research into lupus has long been hampered by failures of medications that initially seemed promising. Now, a coalition of drugmakers, federal regulators, and activists has come together to forge a path toward better-designed studies and – potentially – groundbreaking new drugs.

“We have an opportunity to work collaboratively in lupus to address the challenges in drug development,” Teodora Staeva, PhD, vice president and chief scientific officer of the Lupus Research Alliance, said in an interview.

The alliance held a press conference on March 29 to announce the formation of the public-private Lupus Accelerating Breakthroughs Consortium. Coalition members include several major drugmakers, lupus organizations such as the LRA, the American College of Rheumatology, the Food and Drug Administration, and other federal agencies. Academic researchers, people living with lupus, caregivers and family members, and other members of the lupus community are also on board.

As Dr. Staeva explained, research into lupus has been marked by a high rate of failure. “Often, phase 2 trial successes have not translated into phase 3 successes,” she said.

But researchers, she said, don’t tend to think this is because the drugs themselves are useless.

Instead, it appears that “trial designs are not adequate to capture meaningful readouts of the drug effects, and that may have contributed to the multiple failures,” she said.

According to her, this may because the trials aren’t yet designed to fully detect whether drugs are useful. This is difficult to accomplish since patients have so many manifestations of the disease and trial participants already take a variety of existing drugs.

“Another major limitation has been the lack of integration of the patient’s voice and needs in the drug development process,” she said. It’s also challenging to recruit patients with the most severe lupus to participate in studies, especially since the trials often last 52 weeks.

The new coalition will not directly develop or favor specific drugs. Instead, it will focus on clinical research priorities. “It’s all open and collaborative,” Dr. Staeva explained, and a patient council will provide input. “We have a unique opportunity to bring the voice of people [living with lupus] to the table for the first time and be able to integrate their needs and priorities into the infrastructure.”

The new coalition was inspired by existing public-private partnerships such as the Kidney Health Initiative, she said. That initiative was founded in 2012 by the FDA and the American Society of Nephrology and has dozens of members, including multiple drugmakers and medical societies.

The leadership of the Lupus ABC coalition will include three nonvoting members from the FDA. They’ll offer guidance, Dr. Staeva said. At the press conference, Albert T. Roy, president and CEO of the LRA, said drug companies will appreciate the opportunity to speak with FDA representatives “in a space that is not competitive with respect to intellectual property or anything like that.”

The coalition will meet later in spring 2023, Dr. Staeva said. She hopes it will launch a couple of projects by the end of 2023 and be able to release preliminary results by the end of 2024.

One challenge will be figuring out how to stratify trial subjects so drug studies will more easily detect medications that may work in smaller populations of patients, Hoang Nguyen, PhD, director of scientific partnerships at the LRA, said in an interview. “Now we lump [patients] all together, and that’s not the optimal way to test drugs on patients who have a lot of differences.”

According to Dr. Staeva, the LRA funded the development of the coalition, and drugmakers will primarily provide financial support going forward. The pharmaceutical company members of the coalition are Biogen, Bristol-Myers Squibb, Eli Lilly, EMD Serono, Genentech, Gilead, GlaxoSmithKline, Merck, and Takeda.

Dr. Staeva, Dr. Nguyen, and Mr. Roy have no disclosures.

Clinical research into lupus has long been hampered by failures of medications that initially seemed promising. Now, a coalition of drugmakers, federal regulators, and activists has come together to forge a path toward better-designed studies and – potentially – groundbreaking new drugs.

“We have an opportunity to work collaboratively in lupus to address the challenges in drug development,” Teodora Staeva, PhD, vice president and chief scientific officer of the Lupus Research Alliance, said in an interview.

The alliance held a press conference on March 29 to announce the formation of the public-private Lupus Accelerating Breakthroughs Consortium. Coalition members include several major drugmakers, lupus organizations such as the LRA, the American College of Rheumatology, the Food and Drug Administration, and other federal agencies. Academic researchers, people living with lupus, caregivers and family members, and other members of the lupus community are also on board.

As Dr. Staeva explained, research into lupus has been marked by a high rate of failure. “Often, phase 2 trial successes have not translated into phase 3 successes,” she said.

But researchers, she said, don’t tend to think this is because the drugs themselves are useless.

Instead, it appears that “trial designs are not adequate to capture meaningful readouts of the drug effects, and that may have contributed to the multiple failures,” she said.

According to her, this may because the trials aren’t yet designed to fully detect whether drugs are useful. This is difficult to accomplish since patients have so many manifestations of the disease and trial participants already take a variety of existing drugs.

“Another major limitation has been the lack of integration of the patient’s voice and needs in the drug development process,” she said. It’s also challenging to recruit patients with the most severe lupus to participate in studies, especially since the trials often last 52 weeks.

The new coalition will not directly develop or favor specific drugs. Instead, it will focus on clinical research priorities. “It’s all open and collaborative,” Dr. Staeva explained, and a patient council will provide input. “We have a unique opportunity to bring the voice of people [living with lupus] to the table for the first time and be able to integrate their needs and priorities into the infrastructure.”

The new coalition was inspired by existing public-private partnerships such as the Kidney Health Initiative, she said. That initiative was founded in 2012 by the FDA and the American Society of Nephrology and has dozens of members, including multiple drugmakers and medical societies.

The leadership of the Lupus ABC coalition will include three nonvoting members from the FDA. They’ll offer guidance, Dr. Staeva said. At the press conference, Albert T. Roy, president and CEO of the LRA, said drug companies will appreciate the opportunity to speak with FDA representatives “in a space that is not competitive with respect to intellectual property or anything like that.”

The coalition will meet later in spring 2023, Dr. Staeva said. She hopes it will launch a couple of projects by the end of 2023 and be able to release preliminary results by the end of 2024.

One challenge will be figuring out how to stratify trial subjects so drug studies will more easily detect medications that may work in smaller populations of patients, Hoang Nguyen, PhD, director of scientific partnerships at the LRA, said in an interview. “Now we lump [patients] all together, and that’s not the optimal way to test drugs on patients who have a lot of differences.”

According to Dr. Staeva, the LRA funded the development of the coalition, and drugmakers will primarily provide financial support going forward. The pharmaceutical company members of the coalition are Biogen, Bristol-Myers Squibb, Eli Lilly, EMD Serono, Genentech, Gilead, GlaxoSmithKline, Merck, and Takeda.

Dr. Staeva, Dr. Nguyen, and Mr. Roy have no disclosures.

Clinical research into lupus has long been hampered by failures of medications that initially seemed promising. Now, a coalition of drugmakers, federal regulators, and activists has come together to forge a path toward better-designed studies and – potentially – groundbreaking new drugs.

“We have an opportunity to work collaboratively in lupus to address the challenges in drug development,” Teodora Staeva, PhD, vice president and chief scientific officer of the Lupus Research Alliance, said in an interview.

The alliance held a press conference on March 29 to announce the formation of the public-private Lupus Accelerating Breakthroughs Consortium. Coalition members include several major drugmakers, lupus organizations such as the LRA, the American College of Rheumatology, the Food and Drug Administration, and other federal agencies. Academic researchers, people living with lupus, caregivers and family members, and other members of the lupus community are also on board.

As Dr. Staeva explained, research into lupus has been marked by a high rate of failure. “Often, phase 2 trial successes have not translated into phase 3 successes,” she said.

But researchers, she said, don’t tend to think this is because the drugs themselves are useless.

Instead, it appears that “trial designs are not adequate to capture meaningful readouts of the drug effects, and that may have contributed to the multiple failures,” she said.

According to her, this may because the trials aren’t yet designed to fully detect whether drugs are useful. This is difficult to accomplish since patients have so many manifestations of the disease and trial participants already take a variety of existing drugs.

“Another major limitation has been the lack of integration of the patient’s voice and needs in the drug development process,” she said. It’s also challenging to recruit patients with the most severe lupus to participate in studies, especially since the trials often last 52 weeks.

The new coalition will not directly develop or favor specific drugs. Instead, it will focus on clinical research priorities. “It’s all open and collaborative,” Dr. Staeva explained, and a patient council will provide input. “We have a unique opportunity to bring the voice of people [living with lupus] to the table for the first time and be able to integrate their needs and priorities into the infrastructure.”

The new coalition was inspired by existing public-private partnerships such as the Kidney Health Initiative, she said. That initiative was founded in 2012 by the FDA and the American Society of Nephrology and has dozens of members, including multiple drugmakers and medical societies.

The leadership of the Lupus ABC coalition will include three nonvoting members from the FDA. They’ll offer guidance, Dr. Staeva said. At the press conference, Albert T. Roy, president and CEO of the LRA, said drug companies will appreciate the opportunity to speak with FDA representatives “in a space that is not competitive with respect to intellectual property or anything like that.”

The coalition will meet later in spring 2023, Dr. Staeva said. She hopes it will launch a couple of projects by the end of 2023 and be able to release preliminary results by the end of 2024.

One challenge will be figuring out how to stratify trial subjects so drug studies will more easily detect medications that may work in smaller populations of patients, Hoang Nguyen, PhD, director of scientific partnerships at the LRA, said in an interview. “Now we lump [patients] all together, and that’s not the optimal way to test drugs on patients who have a lot of differences.”

According to Dr. Staeva, the LRA funded the development of the coalition, and drugmakers will primarily provide financial support going forward. The pharmaceutical company members of the coalition are Biogen, Bristol-Myers Squibb, Eli Lilly, EMD Serono, Genentech, Gilead, GlaxoSmithKline, Merck, and Takeda.

Dr. Staeva, Dr. Nguyen, and Mr. Roy have no disclosures.

Rheumatologist Marcus Snow, MD, is comfortable with prescribing biosimilars as a first-line, first-time biologic, and discussing them with patients.

“If a biosimilar is on the market, it has gone through rigorous study proving its effectiveness and equivalence to a bio-originator,” said Dr. Snow, a rheumatologist with the University of Nebraska Medical Center, Omaha, and chair of the American College of Rheumatology’s Committee on Rheumatologic Care.

The formulary makes a big difference in the conversation about options, he said. “The formularies dictate what we can prescribe. It may not be appropriate, but it is reality. The cost of biologics for a patient without insurance coverage makes it impossible to afford.”

He will often tell patients that he’ll fight any changes or formulary restrictions he does not agree with. “However, when I see patients in follow-up, even if there is no known change on the horizon, I may bring up biosimilars when we have a moment to chat about them to familiarize them with what may happen in the future.”

The need for patient education on biosimilars presents a barrier to realizing their potential to save money and expand choice, noted Cardinal Health in its 2023 biosimilars report. Of 103 rheumatologists who responded to a Cardinal Health survey, 85% agreed that patient education was important. But those conversations can take an uncomfortable turn if the patient pushes back against taking a biosimilar owing to cost or safety concerns.

It’s not uncommon for a patient to express some anxiety about biosimilars, especially if they’re doing well on a current treatment plan. Most patients do not want any changes that may lead to worsening disease control, Dr. Snow said.

Kaiser Permanente

Patients and physicians alike often don’t understand the mechanics of biosimilars. “There’s a lot of misinformation about this,” said Sameer Awsare, MD, an associate executive director for The Permanente Medical Group in Campbell, Calif. Patients should know that a biosimilar will be as clinically efficacious as the medicine they’ve been on, with the same safety profiles, said Dr. Awsare, who works with Kaiser Permanente’s pharmacy partners on biosimilars.
 

Insurance often drives the conversation

The global anti-inflammatory biologics market is anticipated to reach $150 billion by 2027, according to a recent CVS report. As of March 2023, the Food and Drug Administration had approved 40 biosimilars to 11 different reference products. There are 28 on the U.S. market and 100 more in development. Projected to save more than $180 billion over the next 5 years, they are anticipated to expand choice and drive competition.

Rheumatologists, dermatologists, and gastroenterologists are frequent prescribers, although their choices for immune-mediated inflammatory diseases are limited to tumor necrosis factor inhibitors (infliximab [Remicade] originator and adalimumab [Humira] originator) and anti-CD20 agents, such as rituximab (Rituxan) originator.

Benefit design or formulary usually dictates what medicine a patient receives. “Because of significantly higher out-of-pocket cost or formulary positioning, patients may end up with a generic or a biosimilar instead of a brand-name medicine or branded biologic,” said Robert Popovian, PharmD, MS, chief science policy officer of the Global Healthy Living Foundation.

Insurers rarely offer both Remicade and biosimilar infliximab, allowing the doctor to choose, said Miguel Regueiro, MD, chair of the Cleveland Clinic’s Digestive Disease & Surgery Institute, who prescribes infliximab biosimilars. Most often, the payer will choose the lower-cost biosimilar. “I am fine with the biosimilar, either as a new start or a switch from the reference product.”

However, the patient might feel differently. They can form an attachment to the reference medication if it has prevented severe illness. “They do not want to change, as they feel they are going on a ‘new’ medication that will not work as well,” Dr. Regueiro said.

This is where the education comes in: to reassure patients that a biosimilar will work just as well as the reference product. “For patients who have done well for years on a biologic, more time needs to be spent reassuring them and answering questions,” compared with a patient just starting on a biosimilar, he advised.

But not all physicians are quick to prescribe biosimilars.

Julie Miller Photography

Especially with psoriasis, which has so many strong options for reference drugs, a switch may be hard to justify, said dermatologist Stephanie K. Fabbro, MD, assistant professor at Northeast Ohio Medical University, Rootstown. “If I have a preference, I would rather switch a patient to a drug from a different class without a biosimilar option to reduce the possibility of pushback.”

Dr. Fabbro, part of the core faculty in the Riverside Methodist Hospital Dermatology Residency Program in Columbus, will share data from clinical trials and postmarket surveillance with patients to support her decision.
 

Conversations about cost

Patients may also push back if they don’t save money when switching to a biosimilar. “This dilemma raises the question of who is profiting when a biosimilar is dispensed,” Dr. Popovian said. Insurers and pharmacy benefit managers (PBMs) that take additional concessions from biopharmaceutical manufacturers in the form of rebates and fees will often pocket this money as profit instead of passing savings back to the patient to help reduce their out-of-pocket requirement, he added.

If an originator biologic and a biosimilar are available, “as a pharmacist, I will choose the medicine that will incur the lowest out-of-pocket cost for the patient,” Dr. Popovian said.

Discussing cost – and who dictates which biosimilar is on the formulary – is an important conversation to have with patients, said Vivek Kaul, MD, Segal-Watson Professor of Medicine at the University of Rochester (N.Y.) Medical Center.

Providing equivalent clinical efficacy while saving costs is the economic reality of biosimilars, Dr. Kaul said. Third-party payers regularly evaluate how to provide the same quality of care while saving money. Physicians and patients alike “must be mindful that as time goes on, if the science on biosimilars stays robust, if the adoption is more widespread and the cost-saving proposition turns out to be true, more formularies will be attracted to replacing the reference product with the biosimilar counterpart.”

Providers and patients can weigh the options if a formulary suddenly switches to a biosimilar, Dr. Kaul continued. “You can accept the novel product on the formulary or may have to face out-of-pocket expenses as a patient.” If providers and patients have concerns about the biosimilar, they can always appeal if there’s solid scientific evidence that supports reverting back to the reference product.

“If you think the biosimilar is equally efficacious, comes at a lower cost, and is right for the patient, then the providers should tell the patient that,” he added.

Some studies have questioned whether the biosimilars will save money, compared with the reference drug, Dr. Fabbro noted. Medicare, for example, may pay only for a certain percentage of an approved biosimilar, saddling the patient with a monthly copay costing thousands of dollars. “It is unclear whether biosimilar manufacturers will have the same level of patient support programs as the reference drug companies.”

For that reason, physicians should also inform patients about the robust patient assistance and copay assistance programs many reference drug manufacturers offer, she said.

Biosimilars 101: Familiarizing patients

Safety and ease of use are other common concerns about biosimilars. Patients may ask if the application is different, or why it’s advantageous to switch to a biosimilar, Dr. Awsare said.

Sometimes the syringe or injector for a biosimilar might look different from that of the originator drug, he said.

Anecdotally, Dr. Fabbro has heard stories of patients having injection reactions that they did not experience with the reference drug or having a disease flare-up after starting a biosimilar. 

rubberball/Getty Images

As is the case with reference products, in their conversations with patients, clinicians should address the adverse event profile of biosimilars, offering data points from published studies and clinical guidelines that support the use of these products. “There should be an emphasis on patient education around efficacy and any side effects, and how the profile of the reference product compares with a proposed biosimilar,” Dr. Kaul suggested.

When Dr. Snow discusses biosimilars and generics, “I make sure to share this in an understandable way based on the patient’s scientific background, or lack thereof,” he said. If there is enough time, he also discusses how European- and U.S.-sourced biologics are slightly different.

Pharmacists should tell patients to expect the same clinical outcomes from a biosimilar, Dr. Popovian said. However, if they have any reduction in efficacy or potential safety concerns, they should communicate with their physician or pharmacist immediately.

In Dr. Regueiro’s practice, a pharmacist specializing in inflammatory bowel disease often has a one-on-one meeting with patients to educate and answer questions. “Additionally, we provide them the Crohn’s and Colitis Foundation web link on biosimilars,” said Dr. Regueiro.
 

A village approach to education

When biosimilars first came out, there were no formal education materials, Dr. Awsare said. Kaiser Permanente decided to create its own educational materials, not just for patients but also to help educate its primary care doctors; the rheumatologists, dermatologists, and gastroenterologists using the biosimilars; the nurses infusing patients; and the pharmacists preparing the biosimilars.

The health system also has a different approach to choosing medication. Instead of having an insurance company or PBM decide what’s in the formulary, clinicians work with the pharmacists at Kaiser to look at clinical evidence and decide which biosimilar to use. Most of its plans also provide lower copays to patients when they use the biosimilar. 

This was the approach for Humira biosimilars, Dr. Awsare said. Eight will be on the market in 2023. “Our rheumatologists, dermatologists, and gastroenterologists looked at the data from Europe, looked at some real-world evidence, and then said: ‘We think this one’s going to be the best one for our patients.’ ”

Having clinicians choose the biosimilar instead of a health plan makes it a lot easier to have conversations with patients, he said. “Once we’ve moved that market share to that particular biosimilar, we give our physicians the time to have those discussions.”

Clinical pharmacists also provide educational support, offering guidance on issues such as side effects, as patients transition to the biosimilar. “We like to use the word ‘transition’ because it’s essentially the same biologic. So, you’re not actually switching,” Dr. Awsare said.

No consensus on interchangeability

Whether the conversation on interchangeability will affect patient conversations with physicians depends on who you ask.

If a biosimilar has an interchangeability designation, it means that the pharmacist can substitute it without the intervention of the clinician who prescribed the reference product. It does not relate to the quality, safety, or effectiveness of biosimilars or interchangeable biosimilar products, Dr. Popovian said.

The United States is the only country that has this designation. Even though it’s not identical to the originator drug, a biosimilar has the same clinical efficacy and safety profile. “So clinically, interchangeability is meaningless,” Dr. Awsare said.

In its report on biosimilars in the autoimmune category, CVS acknowledged that interchangeability was important but would not be a significant factor in driving adoption of biosimilars. However, in a Cardinal Health survey of 72 gastroenterologists, 38% cited the interchangeability of biosimilars as a top concern for adalimumab biosimilars, along with transitioning patients from Humira to a biosimilar (44%).

“Patient education regarding biosimilar safety, efficacy, and interchangeability appears paramount to the acceptance of these products, particularly for patients who are switched from a reference product,” Dr. Kaul noted in the Cardinal Health report.

Wherever supported by data, Dr. Kaul recommends incorporating biosimilar use and interchangeability into best practice guidelines going forward. “That will go a long way in disseminating the latest information on this topic and position this paradigm for increased adoption among providers.”

Some physicians like Dr. Snow aren’t that concerned with interchangeability. This hasn’t affected conversations with patients, he said. Multiple studies demonstrating the lack of antibody formation with multiple switches from different biosimilar drugs has eased his concern about multiple switches causing problems.

“Initially, there was a gap in demonstrating the long-term effect of multiple switches on antibody production and drug effectiveness. That gap has started to close as more data from Europe’s experience with biosimilars becomes available,” Dr. Snow said.
 

Resources for physicians, patients

The federal government has taken steps to advance biosimilars education and adoption. In 2021, President Biden signed the Advancing Education on Biosimilars Act into law, which directs the FDA to develop or improve continuing education programs that address prescribing of biosimilars and biological products.

The FDA provides educational materials on its website, including a comprehensive curriculum toolkit. The Accreditation Council for Medical Affairs has also created an online 40-hour curriculum for health care professionals called the Board-Certified Biologics and Biosimilars Specialist Program.

Dr. Fabbro recommended patients use the FDA page Biosimilar Basics for Patients to educate themselves on biosimilars. The Global Healthy Living Foundation’s podcast, Breaking Down Biosimilars, is another free resource for patients.

“While much has changed, the continued need for multistakeholder education, awareness, and dedicated research remains even more important as we expand into newer therapeutic areas and classes,” wrote the authors of the Cardinal Health report.

Help patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.

Dr. Regueiro is on advisory boards and consults for AbbVie, Janssen, UCB, Takeda, Pfizer, Bristol-Myers Squibb, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, TARGET PharmaSolutions, Trellis, and Boehringer Ingelheim. Dr. Fabbro is a principal investigator for Castle Biosciences, on the speakers bureau for Valchlor, and on the advisory boards of Janssen and Bristol-Myers Squibb. Dr. Popovian, Dr. Snow, Dr. Awsare, and Dr. Kaul had no disclosures.

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

Rheumatologist Marcus Snow, MD, is comfortable with prescribing biosimilars as a first-line, first-time biologic, and discussing them with patients.

“If a biosimilar is on the market, it has gone through rigorous study proving its effectiveness and equivalence to a bio-originator,” said Dr. Snow, a rheumatologist with the University of Nebraska Medical Center, Omaha, and chair of the American College of Rheumatology’s Committee on Rheumatologic Care.

The formulary makes a big difference in the conversation about options, he said. “The formularies dictate what we can prescribe. It may not be appropriate, but it is reality. The cost of biologics for a patient without insurance coverage makes it impossible to afford.”

He will often tell patients that he’ll fight any changes or formulary restrictions he does not agree with. “However, when I see patients in follow-up, even if there is no known change on the horizon, I may bring up biosimilars when we have a moment to chat about them to familiarize them with what may happen in the future.”

The need for patient education on biosimilars presents a barrier to realizing their potential to save money and expand choice, noted Cardinal Health in its 2023 biosimilars report. Of 103 rheumatologists who responded to a Cardinal Health survey, 85% agreed that patient education was important. But those conversations can take an uncomfortable turn if the patient pushes back against taking a biosimilar owing to cost or safety concerns.

It’s not uncommon for a patient to express some anxiety about biosimilars, especially if they’re doing well on a current treatment plan. Most patients do not want any changes that may lead to worsening disease control, Dr. Snow said.

Kaiser Permanente

Patients and physicians alike often don’t understand the mechanics of biosimilars. “There’s a lot of misinformation about this,” said Sameer Awsare, MD, an associate executive director for The Permanente Medical Group in Campbell, Calif. Patients should know that a biosimilar will be as clinically efficacious as the medicine they’ve been on, with the same safety profiles, said Dr. Awsare, who works with Kaiser Permanente’s pharmacy partners on biosimilars.
 

Insurance often drives the conversation

The global anti-inflammatory biologics market is anticipated to reach $150 billion by 2027, according to a recent CVS report. As of March 2023, the Food and Drug Administration had approved 40 biosimilars to 11 different reference products. There are 28 on the U.S. market and 100 more in development. Projected to save more than $180 billion over the next 5 years, they are anticipated to expand choice and drive competition.

Rheumatologists, dermatologists, and gastroenterologists are frequent prescribers, although their choices for immune-mediated inflammatory diseases are limited to tumor necrosis factor inhibitors (infliximab [Remicade] originator and adalimumab [Humira] originator) and anti-CD20 agents, such as rituximab (Rituxan) originator.

Benefit design or formulary usually dictates what medicine a patient receives. “Because of significantly higher out-of-pocket cost or formulary positioning, patients may end up with a generic or a biosimilar instead of a brand-name medicine or branded biologic,” said Robert Popovian, PharmD, MS, chief science policy officer of the Global Healthy Living Foundation.

Insurers rarely offer both Remicade and biosimilar infliximab, allowing the doctor to choose, said Miguel Regueiro, MD, chair of the Cleveland Clinic’s Digestive Disease & Surgery Institute, who prescribes infliximab biosimilars. Most often, the payer will choose the lower-cost biosimilar. “I am fine with the biosimilar, either as a new start or a switch from the reference product.”

However, the patient might feel differently. They can form an attachment to the reference medication if it has prevented severe illness. “They do not want to change, as they feel they are going on a ‘new’ medication that will not work as well,” Dr. Regueiro said.

This is where the education comes in: to reassure patients that a biosimilar will work just as well as the reference product. “For patients who have done well for years on a biologic, more time needs to be spent reassuring them and answering questions,” compared with a patient just starting on a biosimilar, he advised.

But not all physicians are quick to prescribe biosimilars.

Julie Miller Photography

Especially with psoriasis, which has so many strong options for reference drugs, a switch may be hard to justify, said dermatologist Stephanie K. Fabbro, MD, assistant professor at Northeast Ohio Medical University, Rootstown. “If I have a preference, I would rather switch a patient to a drug from a different class without a biosimilar option to reduce the possibility of pushback.”

Dr. Fabbro, part of the core faculty in the Riverside Methodist Hospital Dermatology Residency Program in Columbus, will share data from clinical trials and postmarket surveillance with patients to support her decision.
 

Conversations about cost

Patients may also push back if they don’t save money when switching to a biosimilar. “This dilemma raises the question of who is profiting when a biosimilar is dispensed,” Dr. Popovian said. Insurers and pharmacy benefit managers (PBMs) that take additional concessions from biopharmaceutical manufacturers in the form of rebates and fees will often pocket this money as profit instead of passing savings back to the patient to help reduce their out-of-pocket requirement, he added.

If an originator biologic and a biosimilar are available, “as a pharmacist, I will choose the medicine that will incur the lowest out-of-pocket cost for the patient,” Dr. Popovian said.

Discussing cost – and who dictates which biosimilar is on the formulary – is an important conversation to have with patients, said Vivek Kaul, MD, Segal-Watson Professor of Medicine at the University of Rochester (N.Y.) Medical Center.

Providing equivalent clinical efficacy while saving costs is the economic reality of biosimilars, Dr. Kaul said. Third-party payers regularly evaluate how to provide the same quality of care while saving money. Physicians and patients alike “must be mindful that as time goes on, if the science on biosimilars stays robust, if the adoption is more widespread and the cost-saving proposition turns out to be true, more formularies will be attracted to replacing the reference product with the biosimilar counterpart.”

Providers and patients can weigh the options if a formulary suddenly switches to a biosimilar, Dr. Kaul continued. “You can accept the novel product on the formulary or may have to face out-of-pocket expenses as a patient.” If providers and patients have concerns about the biosimilar, they can always appeal if there’s solid scientific evidence that supports reverting back to the reference product.

“If you think the biosimilar is equally efficacious, comes at a lower cost, and is right for the patient, then the providers should tell the patient that,” he added.

Some studies have questioned whether the biosimilars will save money, compared with the reference drug, Dr. Fabbro noted. Medicare, for example, may pay only for a certain percentage of an approved biosimilar, saddling the patient with a monthly copay costing thousands of dollars. “It is unclear whether biosimilar manufacturers will have the same level of patient support programs as the reference drug companies.”

For that reason, physicians should also inform patients about the robust patient assistance and copay assistance programs many reference drug manufacturers offer, she said.

Biosimilars 101: Familiarizing patients

Safety and ease of use are other common concerns about biosimilars. Patients may ask if the application is different, or why it’s advantageous to switch to a biosimilar, Dr. Awsare said.

Sometimes the syringe or injector for a biosimilar might look different from that of the originator drug, he said.

Anecdotally, Dr. Fabbro has heard stories of patients having injection reactions that they did not experience with the reference drug or having a disease flare-up after starting a biosimilar. 

rubberball/Getty Images

As is the case with reference products, in their conversations with patients, clinicians should address the adverse event profile of biosimilars, offering data points from published studies and clinical guidelines that support the use of these products. “There should be an emphasis on patient education around efficacy and any side effects, and how the profile of the reference product compares with a proposed biosimilar,” Dr. Kaul suggested.

When Dr. Snow discusses biosimilars and generics, “I make sure to share this in an understandable way based on the patient’s scientific background, or lack thereof,” he said. If there is enough time, he also discusses how European- and U.S.-sourced biologics are slightly different.

Pharmacists should tell patients to expect the same clinical outcomes from a biosimilar, Dr. Popovian said. However, if they have any reduction in efficacy or potential safety concerns, they should communicate with their physician or pharmacist immediately.

In Dr. Regueiro’s practice, a pharmacist specializing in inflammatory bowel disease often has a one-on-one meeting with patients to educate and answer questions. “Additionally, we provide them the Crohn’s and Colitis Foundation web link on biosimilars,” said Dr. Regueiro.
 

A village approach to education

When biosimilars first came out, there were no formal education materials, Dr. Awsare said. Kaiser Permanente decided to create its own educational materials, not just for patients but also to help educate its primary care doctors; the rheumatologists, dermatologists, and gastroenterologists using the biosimilars; the nurses infusing patients; and the pharmacists preparing the biosimilars.

The health system also has a different approach to choosing medication. Instead of having an insurance company or PBM decide what’s in the formulary, clinicians work with the pharmacists at Kaiser to look at clinical evidence and decide which biosimilar to use. Most of its plans also provide lower copays to patients when they use the biosimilar. 

This was the approach for Humira biosimilars, Dr. Awsare said. Eight will be on the market in 2023. “Our rheumatologists, dermatologists, and gastroenterologists looked at the data from Europe, looked at some real-world evidence, and then said: ‘We think this one’s going to be the best one for our patients.’ ”

Having clinicians choose the biosimilar instead of a health plan makes it a lot easier to have conversations with patients, he said. “Once we’ve moved that market share to that particular biosimilar, we give our physicians the time to have those discussions.”

Clinical pharmacists also provide educational support, offering guidance on issues such as side effects, as patients transition to the biosimilar. “We like to use the word ‘transition’ because it’s essentially the same biologic. So, you’re not actually switching,” Dr. Awsare said.

No consensus on interchangeability

Whether the conversation on interchangeability will affect patient conversations with physicians depends on who you ask.

If a biosimilar has an interchangeability designation, it means that the pharmacist can substitute it without the intervention of the clinician who prescribed the reference product. It does not relate to the quality, safety, or effectiveness of biosimilars or interchangeable biosimilar products, Dr. Popovian said.

The United States is the only country that has this designation. Even though it’s not identical to the originator drug, a biosimilar has the same clinical efficacy and safety profile. “So clinically, interchangeability is meaningless,” Dr. Awsare said.

In its report on biosimilars in the autoimmune category, CVS acknowledged that interchangeability was important but would not be a significant factor in driving adoption of biosimilars. However, in a Cardinal Health survey of 72 gastroenterologists, 38% cited the interchangeability of biosimilars as a top concern for adalimumab biosimilars, along with transitioning patients from Humira to a biosimilar (44%).

“Patient education regarding biosimilar safety, efficacy, and interchangeability appears paramount to the acceptance of these products, particularly for patients who are switched from a reference product,” Dr. Kaul noted in the Cardinal Health report.

Wherever supported by data, Dr. Kaul recommends incorporating biosimilar use and interchangeability into best practice guidelines going forward. “That will go a long way in disseminating the latest information on this topic and position this paradigm for increased adoption among providers.”

Some physicians like Dr. Snow aren’t that concerned with interchangeability. This hasn’t affected conversations with patients, he said. Multiple studies demonstrating the lack of antibody formation with multiple switches from different biosimilar drugs has eased his concern about multiple switches causing problems.

“Initially, there was a gap in demonstrating the long-term effect of multiple switches on antibody production and drug effectiveness. That gap has started to close as more data from Europe’s experience with biosimilars becomes available,” Dr. Snow said.
 

Resources for physicians, patients

The federal government has taken steps to advance biosimilars education and adoption. In 2021, President Biden signed the Advancing Education on Biosimilars Act into law, which directs the FDA to develop or improve continuing education programs that address prescribing of biosimilars and biological products.

The FDA provides educational materials on its website, including a comprehensive curriculum toolkit. The Accreditation Council for Medical Affairs has also created an online 40-hour curriculum for health care professionals called the Board-Certified Biologics and Biosimilars Specialist Program.

Dr. Fabbro recommended patients use the FDA page Biosimilar Basics for Patients to educate themselves on biosimilars. The Global Healthy Living Foundation’s podcast, Breaking Down Biosimilars, is another free resource for patients.

“While much has changed, the continued need for multistakeholder education, awareness, and dedicated research remains even more important as we expand into newer therapeutic areas and classes,” wrote the authors of the Cardinal Health report.

Help patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.

Dr. Regueiro is on advisory boards and consults for AbbVie, Janssen, UCB, Takeda, Pfizer, Bristol-Myers Squibb, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, TARGET PharmaSolutions, Trellis, and Boehringer Ingelheim. Dr. Fabbro is a principal investigator for Castle Biosciences, on the speakers bureau for Valchlor, and on the advisory boards of Janssen and Bristol-Myers Squibb. Dr. Popovian, Dr. Snow, Dr. Awsare, and Dr. Kaul had no disclosures.

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

Rheumatologist Marcus Snow, MD, is comfortable with prescribing biosimilars as a first-line, first-time biologic, and discussing them with patients.

“If a biosimilar is on the market, it has gone through rigorous study proving its effectiveness and equivalence to a bio-originator,” said Dr. Snow, a rheumatologist with the University of Nebraska Medical Center, Omaha, and chair of the American College of Rheumatology’s Committee on Rheumatologic Care.

The formulary makes a big difference in the conversation about options, he said. “The formularies dictate what we can prescribe. It may not be appropriate, but it is reality. The cost of biologics for a patient without insurance coverage makes it impossible to afford.”

He will often tell patients that he’ll fight any changes or formulary restrictions he does not agree with. “However, when I see patients in follow-up, even if there is no known change on the horizon, I may bring up biosimilars when we have a moment to chat about them to familiarize them with what may happen in the future.”

The need for patient education on biosimilars presents a barrier to realizing their potential to save money and expand choice, noted Cardinal Health in its 2023 biosimilars report. Of 103 rheumatologists who responded to a Cardinal Health survey, 85% agreed that patient education was important. But those conversations can take an uncomfortable turn if the patient pushes back against taking a biosimilar owing to cost or safety concerns.

It’s not uncommon for a patient to express some anxiety about biosimilars, especially if they’re doing well on a current treatment plan. Most patients do not want any changes that may lead to worsening disease control, Dr. Snow said.

Kaiser Permanente

Patients and physicians alike often don’t understand the mechanics of biosimilars. “There’s a lot of misinformation about this,” said Sameer Awsare, MD, an associate executive director for The Permanente Medical Group in Campbell, Calif. Patients should know that a biosimilar will be as clinically efficacious as the medicine they’ve been on, with the same safety profiles, said Dr. Awsare, who works with Kaiser Permanente’s pharmacy partners on biosimilars.
 

Insurance often drives the conversation

The global anti-inflammatory biologics market is anticipated to reach $150 billion by 2027, according to a recent CVS report. As of March 2023, the Food and Drug Administration had approved 40 biosimilars to 11 different reference products. There are 28 on the U.S. market and 100 more in development. Projected to save more than $180 billion over the next 5 years, they are anticipated to expand choice and drive competition.

Rheumatologists, dermatologists, and gastroenterologists are frequent prescribers, although their choices for immune-mediated inflammatory diseases are limited to tumor necrosis factor inhibitors (infliximab [Remicade] originator and adalimumab [Humira] originator) and anti-CD20 agents, such as rituximab (Rituxan) originator.

Benefit design or formulary usually dictates what medicine a patient receives. “Because of significantly higher out-of-pocket cost or formulary positioning, patients may end up with a generic or a biosimilar instead of a brand-name medicine or branded biologic,” said Robert Popovian, PharmD, MS, chief science policy officer of the Global Healthy Living Foundation.

Insurers rarely offer both Remicade and biosimilar infliximab, allowing the doctor to choose, said Miguel Regueiro, MD, chair of the Cleveland Clinic’s Digestive Disease & Surgery Institute, who prescribes infliximab biosimilars. Most often, the payer will choose the lower-cost biosimilar. “I am fine with the biosimilar, either as a new start or a switch from the reference product.”

However, the patient might feel differently. They can form an attachment to the reference medication if it has prevented severe illness. “They do not want to change, as they feel they are going on a ‘new’ medication that will not work as well,” Dr. Regueiro said.

This is where the education comes in: to reassure patients that a biosimilar will work just as well as the reference product. “For patients who have done well for years on a biologic, more time needs to be spent reassuring them and answering questions,” compared with a patient just starting on a biosimilar, he advised.

But not all physicians are quick to prescribe biosimilars.

Julie Miller Photography

Especially with psoriasis, which has so many strong options for reference drugs, a switch may be hard to justify, said dermatologist Stephanie K. Fabbro, MD, assistant professor at Northeast Ohio Medical University, Rootstown. “If I have a preference, I would rather switch a patient to a drug from a different class without a biosimilar option to reduce the possibility of pushback.”

Dr. Fabbro, part of the core faculty in the Riverside Methodist Hospital Dermatology Residency Program in Columbus, will share data from clinical trials and postmarket surveillance with patients to support her decision.
 

Conversations about cost

Patients may also push back if they don’t save money when switching to a biosimilar. “This dilemma raises the question of who is profiting when a biosimilar is dispensed,” Dr. Popovian said. Insurers and pharmacy benefit managers (PBMs) that take additional concessions from biopharmaceutical manufacturers in the form of rebates and fees will often pocket this money as profit instead of passing savings back to the patient to help reduce their out-of-pocket requirement, he added.

If an originator biologic and a biosimilar are available, “as a pharmacist, I will choose the medicine that will incur the lowest out-of-pocket cost for the patient,” Dr. Popovian said.

Discussing cost – and who dictates which biosimilar is on the formulary – is an important conversation to have with patients, said Vivek Kaul, MD, Segal-Watson Professor of Medicine at the University of Rochester (N.Y.) Medical Center.

Providing equivalent clinical efficacy while saving costs is the economic reality of biosimilars, Dr. Kaul said. Third-party payers regularly evaluate how to provide the same quality of care while saving money. Physicians and patients alike “must be mindful that as time goes on, if the science on biosimilars stays robust, if the adoption is more widespread and the cost-saving proposition turns out to be true, more formularies will be attracted to replacing the reference product with the biosimilar counterpart.”

Providers and patients can weigh the options if a formulary suddenly switches to a biosimilar, Dr. Kaul continued. “You can accept the novel product on the formulary or may have to face out-of-pocket expenses as a patient.” If providers and patients have concerns about the biosimilar, they can always appeal if there’s solid scientific evidence that supports reverting back to the reference product.

“If you think the biosimilar is equally efficacious, comes at a lower cost, and is right for the patient, then the providers should tell the patient that,” he added.

Some studies have questioned whether the biosimilars will save money, compared with the reference drug, Dr. Fabbro noted. Medicare, for example, may pay only for a certain percentage of an approved biosimilar, saddling the patient with a monthly copay costing thousands of dollars. “It is unclear whether biosimilar manufacturers will have the same level of patient support programs as the reference drug companies.”

For that reason, physicians should also inform patients about the robust patient assistance and copay assistance programs many reference drug manufacturers offer, she said.

Biosimilars 101: Familiarizing patients

Safety and ease of use are other common concerns about biosimilars. Patients may ask if the application is different, or why it’s advantageous to switch to a biosimilar, Dr. Awsare said.

Sometimes the syringe or injector for a biosimilar might look different from that of the originator drug, he said.

Anecdotally, Dr. Fabbro has heard stories of patients having injection reactions that they did not experience with the reference drug or having a disease flare-up after starting a biosimilar. 

rubberball/Getty Images

As is the case with reference products, in their conversations with patients, clinicians should address the adverse event profile of biosimilars, offering data points from published studies and clinical guidelines that support the use of these products. “There should be an emphasis on patient education around efficacy and any side effects, and how the profile of the reference product compares with a proposed biosimilar,” Dr. Kaul suggested.

When Dr. Snow discusses biosimilars and generics, “I make sure to share this in an understandable way based on the patient’s scientific background, or lack thereof,” he said. If there is enough time, he also discusses how European- and U.S.-sourced biologics are slightly different.

Pharmacists should tell patients to expect the same clinical outcomes from a biosimilar, Dr. Popovian said. However, if they have any reduction in efficacy or potential safety concerns, they should communicate with their physician or pharmacist immediately.

In Dr. Regueiro’s practice, a pharmacist specializing in inflammatory bowel disease often has a one-on-one meeting with patients to educate and answer questions. “Additionally, we provide them the Crohn’s and Colitis Foundation web link on biosimilars,” said Dr. Regueiro.
 

A village approach to education

When biosimilars first came out, there were no formal education materials, Dr. Awsare said. Kaiser Permanente decided to create its own educational materials, not just for patients but also to help educate its primary care doctors; the rheumatologists, dermatologists, and gastroenterologists using the biosimilars; the nurses infusing patients; and the pharmacists preparing the biosimilars.

The health system also has a different approach to choosing medication. Instead of having an insurance company or PBM decide what’s in the formulary, clinicians work with the pharmacists at Kaiser to look at clinical evidence and decide which biosimilar to use. Most of its plans also provide lower copays to patients when they use the biosimilar. 

This was the approach for Humira biosimilars, Dr. Awsare said. Eight will be on the market in 2023. “Our rheumatologists, dermatologists, and gastroenterologists looked at the data from Europe, looked at some real-world evidence, and then said: ‘We think this one’s going to be the best one for our patients.’ ”

Having clinicians choose the biosimilar instead of a health plan makes it a lot easier to have conversations with patients, he said. “Once we’ve moved that market share to that particular biosimilar, we give our physicians the time to have those discussions.”

Clinical pharmacists also provide educational support, offering guidance on issues such as side effects, as patients transition to the biosimilar. “We like to use the word ‘transition’ because it’s essentially the same biologic. So, you’re not actually switching,” Dr. Awsare said.

No consensus on interchangeability

Whether the conversation on interchangeability will affect patient conversations with physicians depends on who you ask.

If a biosimilar has an interchangeability designation, it means that the pharmacist can substitute it without the intervention of the clinician who prescribed the reference product. It does not relate to the quality, safety, or effectiveness of biosimilars or interchangeable biosimilar products, Dr. Popovian said.

The United States is the only country that has this designation. Even though it’s not identical to the originator drug, a biosimilar has the same clinical efficacy and safety profile. “So clinically, interchangeability is meaningless,” Dr. Awsare said.

In its report on biosimilars in the autoimmune category, CVS acknowledged that interchangeability was important but would not be a significant factor in driving adoption of biosimilars. However, in a Cardinal Health survey of 72 gastroenterologists, 38% cited the interchangeability of biosimilars as a top concern for adalimumab biosimilars, along with transitioning patients from Humira to a biosimilar (44%).

“Patient education regarding biosimilar safety, efficacy, and interchangeability appears paramount to the acceptance of these products, particularly for patients who are switched from a reference product,” Dr. Kaul noted in the Cardinal Health report.

Wherever supported by data, Dr. Kaul recommends incorporating biosimilar use and interchangeability into best practice guidelines going forward. “That will go a long way in disseminating the latest information on this topic and position this paradigm for increased adoption among providers.”

Some physicians like Dr. Snow aren’t that concerned with interchangeability. This hasn’t affected conversations with patients, he said. Multiple studies demonstrating the lack of antibody formation with multiple switches from different biosimilar drugs has eased his concern about multiple switches causing problems.

“Initially, there was a gap in demonstrating the long-term effect of multiple switches on antibody production and drug effectiveness. That gap has started to close as more data from Europe’s experience with biosimilars becomes available,” Dr. Snow said.
 

Resources for physicians, patients

The federal government has taken steps to advance biosimilars education and adoption. In 2021, President Biden signed the Advancing Education on Biosimilars Act into law, which directs the FDA to develop or improve continuing education programs that address prescribing of biosimilars and biological products.

The FDA provides educational materials on its website, including a comprehensive curriculum toolkit. The Accreditation Council for Medical Affairs has also created an online 40-hour curriculum for health care professionals called the Board-Certified Biologics and Biosimilars Specialist Program.

Dr. Fabbro recommended patients use the FDA page Biosimilar Basics for Patients to educate themselves on biosimilars. The Global Healthy Living Foundation’s podcast, Breaking Down Biosimilars, is another free resource for patients.

“While much has changed, the continued need for multistakeholder education, awareness, and dedicated research remains even more important as we expand into newer therapeutic areas and classes,” wrote the authors of the Cardinal Health report.

Help patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars.

Dr. Regueiro is on advisory boards and consults for AbbVie, Janssen, UCB, Takeda, Pfizer, Bristol-Myers Squibb, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, TARGET PharmaSolutions, Trellis, and Boehringer Ingelheim. Dr. Fabbro is a principal investigator for Castle Biosciences, on the speakers bureau for Valchlor, and on the advisory boards of Janssen and Bristol-Myers Squibb. Dr. Popovian, Dr. Snow, Dr. Awsare, and Dr. Kaul had no disclosures.

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