Table 1.
Published epidemiologic studies of isotretinoin use and inflammatory bowel disease, 2009-2014.
| Study | Sample | Design | Results | Limitations |
|---|---|---|---|---|
| Bernstein et al., 2009 | Cases of IBD (n = 2,008) from the Manitoba IBD Epidemiology Database matched to 10 randomly selected controls, aged < 40 years. | Case-control study | Isotretinoin use was not associated with either Crohn's disease (OR = 1.15, 95% CI 0.61, 2.02) or ulcerative colitis (OR = 1.16, 95% CI 0.56, 2.20). | The inclusion of isotreinoin exposures occurring many years before the diagnosis of IBD may have biased the results towards the null. IBD cases were not validated against original medical rcords. No adjustment was made for acne severity or use of antibiotics. |
| Crockett et al., 2010 | 8,189 IBD cases identified using a U.S. insurance claims database and 21,832 matched controls. | Case-control study | Isotretinoin use in the preceding 12 months was associated with ulcerative colitis (odds ratio (OR) = 4.36, 95% confidence interval (CI) 1.97, 9.66) but not Crohn's disease (OR = 0.68, 95% CI 0.28, 1.68). | IBD cases were not validated against original medical rcords. No adjustment was made for acne severity or use of antibiotics. |
| Etminan et al., 2013 | 2,159 cases of IBD from a cohort of women aged 18 to 46 years who had received oral contraceptives and 43,180 matched controls, identified using a U.S. insurance claims database. | Nested case-control study | The adjusted OR for Crohn's disease was 1.10 (95% CO 0.44, 2.70) and the adjusted OR for ulcerative colitis was 1.10 (95% CI 0.44, 2.70). | No adjustment was made for family history of IBD or cigarette smoking. |
| Alhusayen et al. 2013 | 46,922 patients who had been treated with isotretinoin, 184,824 patients who had been treated with topical acne medications, and 1,526,946 who were untreated (referent group), identified using health care records from about 4.5 million residents of British Columbia, Canada. | Population-based retrospective cohort study | No association was observed between treatment with isotretinoin and inflammatory bowel disease (OR = 1.14, 95% CI 0.92, 1.41), except in a subset of patients aged 12 to 19 years (OR = 1.39, 95% CI 1.03, 1.87). | No adjustment was made for family history of IBD or smoking status. A single code was used for IBD. |
| Racine et al., 2014 | A total of 7,593 cases of IBD and 30,372 matched controls, identified using data from the French National Insurance system. | Population-based case-control study | Isotretinoin exposure was not associated with ulcerative colitis (OR = 1.36, 95% CI 0.76, 2.45) but was inversely associated with Crohn's disease (OR = 0.45, 95% CI 0.24, 0.85). | No adjustment was made for cigarette smoking. |
| Rashtak et al., 2014 | The electronic medical records of patients who were primarily seeking acne treatment were reviewed for isotretinoin exposure. The participants included 1,078 patients in Olmsted County, Minnesota. The exposed group included patients with confirmed prior isotretinoin exposure (n = 576), and the nonexposed group were defined as patients who never received isotretinoin or received it after the diagnosis of IBD (n = 502). | Retrospective single center study | Both groups were comparable by race, prior systemic antibiotic use, and systemic tetracycline use. Inflammatory bowel disease developed less frequently in the isotretinoin-exposed group vs. the non-exposed group (0.9% vs 2.6%; P = .03; unadjusted OR = 0.33; 95% CI, 0.12, 0.93; P = .04). The negative association between isotretinoin exposure and IBD remained after adjusting for sex (OR = 0.28; 95% CI, 0.10, 0.80; P = .02) and for sex and non-acne indication (OR = 0.28; 95% CI, 0.10, 0.79; P = .02). | Uncertain generalizability |