Systematic review and meta-analysis: risk of new onset IBD with the use of anti-interleukin-17 agents

Background New onset IBD has been reported with the use of anti-IL-17 agents, but it remains unclear to what extent this is attributed to treatment or to underlying disease. Aim To evaluate the risk of new onset IBD with the use of anti-IL-17 agents Methods Electronic databases were searched for randomised controlled trials (RCT) of anti-IL-17 agents (brodalumab, ixekizumab and secukinumab). Risk of new onset IBD was compared to placebo by Mantel-Haenszel (MH) risk difference (RD). Sensitivity analyses including meta-analysis using fixed-effect model, MH and Peto odds ratio and MH risk ratio were performed due to incidence of rare adverse events. The risk of diarrhoea was also assessed due to the possibility of underdiagnosis of IBD. Results Thirty-eight RCTs including 16 690 patients treated with anti-IL-17 agents were included. Twelve cases of new onset IBD were reported with anti-IL-17 agents in five studies, whereas no cases were reported with placebo. There was no difference in the risk of developing new onset IBD with anti-IL-17 agents compared to placebo (MH RD 0.00062, 95% CI -0.00072-0.0021, P = 0.35). Sensitivity analyses demonstrated no consistent risk with any method. There was no difference in the risk of diarrhoea (MH RD 0.0013, 95% CI -0.0014-0.0041, P = 0.34). Conclusions New onset IBD with the use of anti-IL-17 agents was rare. Interpretation of the results needs caution due to the presence of many zero-event studies.