Short‐term efficacy and safety of new biological agents targeting the interleukin‐23–T helper 17 pathway for moderate‐to‐severe plaque psoriasis: a systematic review and network meta‐analysis

Summary A new generation of biologics targeting the interleukin‐23–T helper 17 pathway has been developed. This study aimed to assess the short‐term effectiveness and safety of these new agents using a network meta‐analysis. Twenty‐seven randomized clinical trials (10 629 patients) were identified by a comprehensive systematic literature review (PROSPERO 2015: CRD42015025472). Quality of evidence was assessed following Cochrane‐compliant rules and the Grading of Recommendations, Assessment, Development and Evaluations approach. Efficacy and safety outcomes at weeks 10–16 were compared using a random‐effects network meta‐analysis within a frequentist framework to estimate pooled odds ratios (ORs) of direct and indirect comparisons among the therapeutic options. There were six direct drug‐to‐drug comparisons in the network, with a high degree of consistency between the direct and indirect evidence. From the available evidence, infliximab 5 mg kg−1 every 8 weeks [OR 118·89, 95% confidence interval (CI) 60·91–232·04] and secukinumab 300 mg every 4 weeks (OR 87·07, 95% CI 55·01–137·82) are shown to be among the most effective short‐term treatments, but are ranked as the biologics most likely to produce any adverse event or an infectious adverse event, respectively. Ustekinumab 90 mg every 12 weeks, the third most efficacious treatment (OR 73·67, 95% CI 46·97–115·56), was the only agent that did not show increased risk of adverse events compared with placebo. Treatment recommendations should also consider long‐term outcomes and costs. What's already known about this topic? Old antitumour necrosis factor‐α agents and recently licensed drugs blocking the interleukin‐23–T helper 17 pathway are more efficacious than placebo for the treatment of moderate‐to‐severe plaque psoriasis. Traditionally, meta‐analyses have usually compared only two interventions at a time, but the need to summarize a comprehensive and coherent set of comparisons based on all of the available evidence has led more recently to synthetic methods that address multiple interventions. What does this study add? To the best of our knowledge, this is the first network meta‐analysis to study the comparative short‐term efficacy and safety of these agents using the new 2015 PRISMA statement for network meta‐analyses. Infliximab and secukinumab ranked as the most efficacious drugs, but with the highest risk for any adverse event and associated infections, respectively. Ustekinumab was the agent with the