Re-evaluation of the risk for major adverse cardiovascular events in patients treated with anti-IL-12/23 biological agents for chronic plaque psoriasis: a meta-analysis of randomized controlled trials

Objective To detect a detrimental or beneficial effect of anti-IL-12/23 biological agents (ustekinumab and briakinumab) for the treatment of chronic plaque psoriasis on major adverse cardiovascular events (MACEs). Design Systematic review and meta-analysis MEDLINE, EMBASE, the Cochrane Skin Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, SciVerse Scopus and ongoing trial registries were searched from inception until December 2011. Search strategy, eligibility criteria, data and statistical analysis methods were defined prior to the literature search. Randomized, placebo-controlled, double-blind, monotherapy studies with safety data for MACEs of IL-12/23 antibodies in adults were eligible for inclusion. Studies of psoriatic arthritis were excluded. Information from each study was extracted independently by two reviewers, using a standardized data extraction form. The primary outcome measure was the number of MACEs during the placebo-controlled phase of treatment. Results MACEs include myocardial infarction, cerebrovascular accident or cardiovascular death. No statistical heterogeneity across the studies using the I2 statistic (I2=0) was found. We employed Peto one-step method to determine odds ratios and quantify a possible detrimental or beneficial association of IL-12/23 antibodies treatment with MACEs. We found a possible higher risk of MACEs in those patients treated with IL-12/23 antibodies compared with those at placebo (OR=4.23, 95% CI: 1.0716.75, P=0.04). This study is unaffected by non-reporting of outcomes with no events. Conclusion Compared with placebo, there was a significant difference in the rate of MACEs observed in patients receiving anti-IL-12/23 biological agents.