BACKGROUND: Evidence on the comparative cardiovascular safety of ustekinumab in psoriasis (PsO) and psoriatic arthritis (PsA) remains limited. OBJECTIVE: To assess risk of major adverse cardiovascular events (MACE) among PsO and PsA patients treated with ustekinumab compared to those treated with adalimumab, etanercept, or secukinumab in routine clinical practice. METHODS: This new-user, active-comparator, observational cohort study used patient-level data from Swedish national registers, including adult PsO/PsA patients initiating treatment with ustekinumab or a comparator between 2009-2021, with patients assigned to mutually exclusive cohorts. The primary outcome was incident MACE, defined as myocardial infarction, ischemic stroke, or cardiovascular-related death. Adjusted hazard ratios (HR) were estimated using cause-specific Cox regression with stabilized inverse probability of treatment weighting by propensity scores. RESULTS: A total of 15,502 patients were included (852 ustekinumab-treated), with 147 MACE observed during follow-up. Adjusted HRs (95% CI) comparing ustekinumab to adalimumab, etanercept, and secukinumab were 1.07 (0.49-2.33), 1.08 (0.48-2.42), and 1.19 (0.46-3.10), respectively. LIMITATIONS: Observational study, drug allocation not randomized, and lack of disease severity data. CONCLUSION: This nationwide study of Swedish PsO/PsA patients spanning >
10 years found no evidence of different cardiovascular safety profiles of ustekinumab versus adalimumab, etanercept, or secukinumab in real-world clinical practice.