Interleukin-17 Inhibitors and Early Major Adverse Cardiovascular Events

Importance The cardiovascular impact of biologics used in psoriasis is not fully understood. Several studies have suggested that the inhibition of the T-helper 17 cell pathway could lead to the destabilization of atherosclerotic plaques, leading to major adverse cardiovascular events (MACEs). Objective To assess whether the initiation of interleukin (IL)-17(R)A inhibitors triggers MACEs. Design, Setting, and Participants In this case–time-control study using the French National Health Insurance database, all individuals who received IL-17(R)A inhibitors (secukinumab, ixekizumab, and brodalumab) from 2016 to 2021, were included and classified according to their cardiovascular risk level. The risk period was defined as the 6 months before the MACE, and the reference period as the 6 months before the risk period. The same design for patients who received tumor necrosis factor (TNF)–α inhibitors (adalimumab or etanercept) for similar indications (psoriasis, psoriatic arthritis, ankylosing spondylitis, or juvenile arthritis), as an active comparator. The data analysis was conducted between April 2023 and August 2024. Exposure The initiation of the biologic was screened in both periods. Main Outcomes and Measures The odds ratios (ORs) for the risk of MACEs were assessed following the initiation of IL-17(R)A inhibitors and TNF-α inhibitors independently. Subsequently, the OR for the risk of MACE associated with IL-17(R)A inhibitors was estimated using TNF-α inhibitors as the comparator. Results Among the 34 241 individuals who received an IL-17(R)A inhibitor, 381 MACEs were analyzed, including 176 acute coronary syndromes and 84 ischemic strokes in the main analysis. Initiation of IL-17(R)A inhibitors was not significantly associated with MACEs (OR, 1.25 [95% CI, 0.75-2.08] vs TNF-α inhibitor initiation and MACEs: OR, 0.90 [95% CI, 0.65-1.24]). Overall, the initiation of an IL-17(R)A inhibitor was not significantly associated with MACEs in the following 6 months, using TNF-α inhibitor as a comparator (OR, 1.40 [95% CI, 0.77-2.54]), regardless of the individual cardiovascular risk ( P for homogeneity = .29). The definition of MACE was broadened in a first sensitivity analysis, and the risk period was shortened to 3 months in a second sensitivity analysis. The results did not change. Conclusions In this case–time-control study based on a national insurance database, there was no evidence of a significant association between MACEs and the initiation of IL-17(R)A inhibitors, regardless of the individual cardiovascular risk of the patient. However, a modest risk increase cannot be entirely excluded.