Impact of biologic therapies on risk of major adverse cardiovascular events in patients with psoriasis: systematic review and meta‐analysis of randomized controlled trials

Summary Concerns have been raised regarding an increased risk of major adverse cardiovascular events ( MACE s) (myocardial infarction, cerebrovascular accident or cardiovascular death) in patients treated with anti‐interleukin ( IL )‐12/23 agents for moderate‐to‐severe psoriasis. We aimed to examine the risk of MACE s in adult patients with plaque psoriasis that are exposed to biologic therapies via a meta‐analysis of randomized controlled trials ( RCT s). Data were obtained from systematic searches in the Cochrane Library, MEDLINE and Embase , U.S. Food and Drug Administration, European Medicines Agency, individual pharmaceutical companies online search platforms and five trials registers (up to 31 March 2016). We selected RCT s reporting adverse events in adults with plaque psoriasis receiving at least one licensed dose of biologic therapy, conventional systematic therapy or placebo. We calculated Peto odds ratios ( OR s) with 95% confidence intervals ( CI s) and calculated I 2 statistics to assess heterogeneity. Overall, 38 RCT s involving 18 024 patients were included. No MACE s were observed in 29 studies, while nine RCT s reported 10 patients experiencing MACE s. There was no statistically significant difference in risk of MACE s associated with the use of biologic therapies overall ( OR 1·45, 95% CI 0·34–6·24); tumour necrosis factor‐α inhibitors (adalimumab, etanercept and infliximab) ( OR 0·67, 95% CI 0·10–4·63); anti‐ IL ‐17A agents (secukinumab and ixekizumab) ( OR 1·00, 95% CI 0·09–11·09) or ustekinumab ( OR 4·48, 95% CI 0·24–84·77). No heterogeneity was observed in these comparisons. In conclusion, the limited existing evidence suggests that licensed biologic therapies are not associated with MACE s during the short randomized controlled periods in clinical trials.