Tumor necrosis factor inhibitors and cardiovascular outcomes in adults with moderate-to-severe plaque psoriasis: a systematic review and meta-analysis

BACKGROUND: Moderate-to-severe plaque psoriasis is associated with persistent systemic inflammation and increased cardiovascular risk. OBJECTIVES: To evaluate the association between anti-TNF therapy and clinical cardiovascular outcomes in adults with moderate-to-severe plaque psoriasis. METHODS: The authors conducted a systematic review and meta-analysis in accordance with PRISMA 2020 and prospectively registered the protocol in PROSPERO (CRD420251270784). Randomized controlled trials and comparative observational studies evaluating anti-TNF therapy versus placebo, no anti-TNF exposure, topical therapy and/or phototherapy, or non-biologic systemic therapy were eligible. Outcomes of interest were Major Adverse Cardiovascular Events (MACE), myocardial infarction, stroke, cardiovascular death, heart failure, atrial fibrillation, venous thromboembolism, and all-cause mortality. RESULTS: Fourteen studies were included. In randomized evidence, anti-TNF therapy was not associated with significant differences in the risk of MACE, myocardial infarction, stroke, or heart failure. In observational analyses stratified by comparator, anti-TNF therapy was associated with a lower pooled risk of reported cardiovascular events versus topical therapy, but not versus oral therapy or phototherapy. STUDY LIMITATIONS: The available evidence was limited by short follow-up in randomized trials, low cardiovascular event counts, wide confidence intervals, and indirect assessment of cardiovascular outcomes, as most trials were designed primarily for dermatologic efficacy and general safety rather than cardiovascular endpoints. CONCLUSIONS: Anti-TNF agents were not associated with a clear increase in major cardiovascular risk and appear to have an acceptable short-term cardiovascular safety profile. However, current evidence does not establish a conclusive cardioprotective effect, and larger prospective studies with longer follow-up are needed.