Concomitant antibiotic usage does not augment the risk of inflammatory bowel disease with isotretinoin treatment for acne: a review of the Food and Drug Administration Adverse Event Reporting System

Abstract

To the editor: Evidence varies on whether isotretinoin and/or antibiotics are associated with inflammatory bowel disease (IBD). While earlier studies linked isotretinoin exposure with a subsequent development of IBD [1], other case– control studies have either failed to show this association [2] or only showed it with ulcerative colitis (UC) but not Crohn’s disease (CD) [3]. A study by Margolis et al. utilizing the General Practice Research Database suggested the observed link between isotretinoin and IBD could be the result of previous antibiotic exposure (specifically with the tetracycline family) before isotretinoin usage rather than a primary association with isotretinoin usage [4]. Bernstein et al. utilizing the Manitoba database demonstrated that IBD patients were more likely to have received antibiotics in the 2–5 years prior to the IBD diagnosis [5]. We reviewed all reports of isotretinoin and antibiotic associated IBD in patients with acne in the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS). We sought to investigate whether there is an augmentation in the risk of IBD development with exposure to isotretinoin alone versus isotretinoin and oral antibiotics. We downloaded 2,562,390 files between January 2003 and June 2011 from the FDA AERS and analyzed them using SPSS 20 (IBM Co. Armonk, NY, USA). Because of a potential reporting bias with lawyer initiated reports, only reports from medical professionals and consumers were included in this analysis. A search was conducted for cases of IBD reported with generic and trade names of isotretinoin and oral antibiotics (cephalosporins, penicillins, teracyclines, metronidazole, lincosamides, nitrofurantoin, macrolides, quinolones, and sulfonamides) with an indication of acne. Only cases in which either isotretinoin was listed as primary suspect or one of the oral antibiotics (defined above) were listed as primary suspect were included in the analysis. The cases with antibiotic exposure were stratified into exposure to one, two, or three or more antibiotics. Cases were subdivided between UC and CD, to identify differences in the risk between the two. Furthermore, control reactions (calculus, hernia, joint dislocation, viral infection, herpes, and neoplasm) were pre-defined that were not known to have any association with any of the study drugs. Reports for these control reactions with the study drugs as primary suspect were also included in the analysis. The association for the study drugs with the development of IBD was tested in a two by two table using Fisher’s exact test. Further analysis specific to exposure to tetracycline antibiotics (along with isotretinoin) was also performed. There were 266 cases of IBD with isotretinoin treatment, 37 of which were with antibiotic usage. Compared to isotretinoin usage alone, neither oral antibiotics (p-value00.1209) nor tetracyclines in particular (p-value01.00), augmented the risk of D. J. Stobaugh : P. Deepak : E. D. Ehrenpreis (*) Center for the Study of Complex Diseases, NorthShore University HealthSystem, Evanston, IL, USA e-mail: ehrenpreis@gipharm.net