Isotretinoin Exposure and Risk of Inflammatory Bowel Disease: A Systematic Review with Meta-Analysis and Trial Sequential Analysis.
Background: Cases of inflammatory bowel disease (IBD) following isotretinoin use have been reported previously, but whether isotretinoin exposure is associated with IBD has been unclear.
Objective: The aim was to evaluate whether isotretinoin use is associated with IBD.
Methods: We 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.
Results: We 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%.
Conclusions: This 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. CRD42022298886.