Is Isotretinoin exposure associated with Inflammatory Bowel Disease? A Case Control Study

Abstract

Isotretinoin is commonly prescribed for the treatment of severe acne. Though cases of IBD have been reported in isotretinoin users, the peak age of isotretinoin use coincides with the peak age of the incidence of inflammatory bowel disease (IBD), raising the possibility that these are coincident events. Despite several high profile legal cases involving this connection, a causal association between isotretinoin and IBD remains unproven. To evaluate whether prior exposure to isotretinoin is related to a subsequent diagnosis of IBD. We performed a case-control study, using insurance claims data pooled from 87 different health plans across 33 states (PharMetrics, IMS Health, Watertown, MA). Among individuals with at least 12 months of continuous health plan enrollment, cases of Crohn's disease (CD), ulcerative colitis (UC), and indeterminate IBD were identified using a previously reported administrative definition. Cases were then matched to 3 non-IBD controls on the basis of age, gender, geographical region, health plan, and length of continuous health plan enrollment. Exposure to isotretinoin was assessed in the 12 months prior to the first IBD diagnosis for cases, or in the first 12 months of enrollment for controls. Conditional logistic regression was used to adjust for the matching variables. The study population contained 8,189 cases (3,664 CD and 4,428 UC) and 21,832 controls. Prior isotretinoin use was present in 60 subjects (24 cases and 36 controls). The odds ratio (OR) of IBD for isotretinoin use was 1.68 (95% confidence interval (CI) 0.98, 2.86), adjusted for age, sex, geographic region, health plan, and length of plan enrollment. Ulcerative colitis was strongly associated with prior isotretinoin exposure (OR 4.36, 95% CI 1.97, 9.66). However there was no apparent association between isotretinoin exposure and Crohn's disease (OR 0.68, 95% CI 0.28, 1.68). Increasing dose of isotretinoin was associated with elevated risk of UC (OR per 10 mg increase in dose: 1.23, 95% CI 1.04, 1.45). Those taking isotretinoin for more than 2 months were also at higher risk of UC (OR 5.63, 95% CI 2.10, 15.03). In this case-control study, ulcerative colitis but not Crohn's disease, was associated with prior isotretinoin exposure. The association was stronger with increased isotretinoin dose and duration of therapy. Future studies are indicated to confirm this finding in other populations, and to elucidate possible biological mechanisms by which isotretinoin may lead to IBD. Though the absolute risk of developing IBD in persons who take isotretinoin is likely quite small, clinicians and prospective patients should be aware of this potential association.