Isotretinoin Exposure and Risk of Inflammatory Bowel Disease: A Systematic Review with Meta-Analysis and Trial Sequential Analysis

BackgroundCases of inflammatory bowel disease (IBD) following isotretinoin use have been reported previously, but whether isotretinoin exposure is associated with IBD has been unclear.ObjectiveThe aim was to evaluate whether isotretinoin use is associated with IBD.MethodsWe performed a systematic review and searched MEDLINE, Embase, and CENTRAL databases from inception to January 27, 2023 for relevant case-control and cohort studies. Our outcome was the pooled odds ratio (OR) for IBD and its two subtypes (Crohn disease and ulcerative colitis) in relation to isotretinoin exposure. We conducted a random-effects model meta-analysis and a sensitivity analysis by excluding low-quality studies. A subgroup analysis was undertaken by including studies considering antibiotic use. A trial sequential analysis (TSA) was performed to test the robustness of the conclusiveness of our results.ResultsWe included eight studies (four case-control and four cohort studies) with a total of 2,522,422 participants. The meta-analysis found no increased odds for IBD among patients receiving isotretinoin (OR 1.01; 95% confidence interval [CI] 0.80-1.27). Nor did the meta-analysis find increased odds for either Crohn disease (OR 0.87; 95% CI 0.65-1.15) or ulcerative colitis (OR 1.27; 95% CI 0.94-1.73) associated with isotretinoin exposure. The sensitivity and subgroup analyses produced similar results. In TSA, the Z-curve reached the futility boundaries when using relative risk reduction thresholds ranging from 5% to 15%.ConclusionThis meta-analysis with TSA found no evidence of an association of isotretinoin use with IBD. Isotretinoin should not be withheld because of unnecessary concerns for the development of IBD.PROSPERO registration noCRD42022298886.

Automated summary

This study conducted a systematic review and meta-analysis, finding no evidence of an association between isotretinoin use and inflammatory bowel disease (IBD). Therefore, isotretinoin should not be withheld due to unnecessary concerns for the development of IBD.