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TOPLINE:

A case-time-control study found no association between the initiation of interleukin 17 (IL-17) receptor A inhibitors and major adverse cardiovascular events (MACEs).

METHODOLOGY:

• Researchers conducted a case-time-control study using data on 34,241 individuals (mean age, 48.5 years; 45% men) receiving an IL-17 receptor A inhibitor (secukinumab, ixekizumab, and brodalumab) from the French National Health Insurance database between July 2016 and December 2021; 59% had psoriasis, 17% had psoriatic arthritis (PsA), 48% had ankylosing spondylitis, 3% had juvenile arthritis, and 29% had high cardiovascular risk.
• They included 108,811 active comparators, patients who received a TNF alpha inhibitor (adalimumab or etanercept) from 2010 to 2021 (42% had psoriasis, 12% had PsA, 63% had ankylosing spondylitis, 8% had juvenile arthritis, and 22% had high cardiovascular risk.)
• For every individual with MACE, the researchers identified four time-controls (age- and sex-matched individuals with a similar level of cardiovascular risk) to adjust for the prescribing trends.
• The primary outcome was MACE (acute coronary syndrome resulting in hospitalization in the ICU or ischemic stroke) after initiating treatment with an IL-17 receptor A inhibitor. The risk period was defined as 6 months before the event, and the reference period as 6-12 months before the event.

TAKEAWAY:

• The crude incidence of MACEs among those treated with IL-17 inhibitors was 3.41 per 1000 patient-years.
• After adjusting for the time trend, initiating an IL-17 receptor A inhibitor was not significantly associated with MACEs in the risk period compared with those on a TNF alpha inhibitor (odds ratio [OR], 1.25; 95% CI, 0.75-2.08).
• After adjusting for the time trend, the OR for an association between initiating a TNF alpha inhibitor and MACE was 0.90 (95% CI, 0.65-1.24).
• After adjustment for confounders and potential discontinuation of cardiovascular protective drugs, there was no significant risk for MACEs within 6 months of initiating an IL-17 receptor A inhibitor, “whatever the baseline cardiovascular risk level of the patient,” the authors of the study reported (OR, 1.40; P = .20).

IN PRACTICE:

“In this case-time-control study, we did not find any trigger effect of the initiation of IL-17 [receptor A] inhibitors for MACEs,” the authors of the study wrote. “While this result provides some reassurance for prescribers and patients, a modest risk cannot be definitively ruled out,” and more studies are still needed “to explore the cardiovascular effects of biologics in immune-mediated diseases,” they added.

SOURCE:

The study was led by Maxime Raby, MD, Department of Dermatology, Université de Rennes, CHU Rennes, Rennes, France. It was published online on September 3 in JAMA Dermatology.

LIMITATIONS:

Drug dispensations were considered as a proxy for actual intake; incomplete clinical data on cardiovascular risk factors could have introduced misclassification bias; the choice of 6 months was random; and finally, there was a suspected lack of power in sample size calculation.

DISCLOSURES:

The study received funding from the French Society of Dermatology. Raby reported grants from Université de Rennes during the conduct of the study. Two authors also reported receiving meeting attendance support, personal fees, honoraria, and grants, from the French Society of Dermatology, Amgen, Sanofi, MSD, and various other sources. Remaining disclosures are included in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.