Risk of Major Cardiovascular Events in Patients with Psoriasis, Psoriatic Arthritis, and/or Other Forms of Spondyloarthritis: A Cohort of 72,291 Biologic New Users

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.

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.

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.

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 47,674 TNFi (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 with TNFi 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.

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.