BioDrugs. 2026 Oct 30. doi: 10.1007/s40259-026-00815-8. Online ahead of print.
ABSTRACT
BACKGROUND: The impact of biologic therapies (biologic disease-modifying antirheumatic drugs [bDMARD]) used in psoriasis (Pso), psoriatic arthritis (PsA), and other forms of spondyloarthritis (SpA) on the risk of major cardiovascular events (MACE) remains controversial.
OBJECTIVE: We aimed to assess the risk of MACE after initiation of a bDMARD among patients with Pso, PsA, or SpA, in a real-world clinical setting.
METHODS: We conducted a nationwide cohort study using the French National Health Data System (SNDS). Adults with Pso, PsA, or SpA who initiated a bDMARD (tumor necrosis factor inhibitors [TNFi]; interleukin [IL] inhibitors: IL-12/23i, IL-23i, IL-17i) between 1 July, 2016, and 31 July, 2023 were eligible for inclusion. The primary outcome was incident MACE, defined as cardiovascular death and/or hospitalization for acute myocardial infarction or ischemic stroke. Inverse probability-weighted Cox models were used to estimate weighted hazard ratios and their confidence intervals. Models were further adjusted for time-varying concomitant treatments, treatment indication, year of initiation, and prior non-steroidal anti-inflammatory drug use. An interaction term between bDMARD exposure and history of cardiovascular disease was included.
RESULTS: A total of 72,291 patients were included (mean age 46.1 ± 14.2 years, 49.4% female): 10,703 IL-17i (14.8%), 7952 IL-23i (11.0%), 5962 IL-12/23i (8.2%), and 47,674TNFi (66.0%). Compared with initiators of other bDMARDs, TNFi initiators were younger and had fewer comorbidities and cardiovascular risk factors at baseline. During follow-up, 438 patients (0.6%) experienced a MACE, including 107 (0.1%) cardiovascular deaths. The median time to event was 13.5 months (interquartile range, 5.1-30.4). In crude analyses, initiation of IL-17i, IL-23i, and IL-12/23i was associated with a higher risk of MACE compared withTNFi drugs. However, among patients without a history of cardiovascular disease, after inverse probability of treatment weighting and adjustment, no significant association was observed (weighted hazard ratio [95% confidence interval]: 0.90 [0.57-1.43] for IL-12/23i, 1.12 [0.66-1.88] for IL-23i, and 1.07 [0.74-1.55] for IL-17i). Findings held across most sensitivity analyses, except for the short-term analysis restricted to the first 6 months after treatment initiation, in which a trend toward a higher MACE risk with IL-17i was observed. A trend toward a higher MACE risk with IL-17i was also observed among men, patients aged ≥ 50 years, and those with a history of non-steroidal anti-inflammatory drug use. However, the number of events was low, and the results did not reach statistical significance.
CONCLUSIONS: No significant increase in MACE risk was observed with IL-12/23i, IL-23i, or IL-17i compared with tumor necrosis factor inhibitors. However, the study lacked sufficient power to draw definitive conclusions regarding a possible increased risk associated with IL-17i in patients with a high baseline cardiovascular risk profile, or the potentiation of this risk by non-steroidal anti-inflammatory drug use.
PMID:42961614 | DOI:10.1007/s40259-026-00815-8