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

• Published in: Alimentary pharmacology & therapeutics Vol. 50; no. 4; pp. 373 - 385
• Main Authors: Yamada, Akihiro, Wang, Jingzhou, Komaki, Yuga, Komaki, Fukiko, Micic, Dejan, Sakuraba, Atsushi
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-08-2019
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Clinical trials; Dermatologic Agents - administration & dosage; Dermatologic Agents - adverse effects; Diarrhea; Humans; Incidence; Inflammatory Bowel Diseases - chemically induced; Inflammatory Bowel Diseases - epidemiology; Interleukin-17 - antagonists & inhibitors; Medical treatment; Meta-analysis; Monoclonal antibodies; Randomized Controlled Trials as Topic - statistics & numerical data; Risk Factors
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/apt.15397

Summary
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.