A-OK for Accutane

Another article has reaffirmed that isotretinoin (Accutane) does not increase the risk of IBD (JAMA Dermatol 2013; 149: 216-20).  Thanks to Mike Hart for this reference. However, this data will not reverse the millions of dollars that have been lost in litigation (Isotretinoin – Wikipedia, the free encyclopedia).

Using a large U.S. health claims database (68 million patients), the authors examined women ages 18-46 years who had received at least one oral contraceptive prescription between 2001-2009.  For each patient with IBD, 20 controls were identified in a nested case-control study design.

In total, 2159 IBD cases (1056 UC, 1103 CD) were matched with 43,180 controls.  Only 10 patients with IBD were exposed to isotretinoin compared with 191 controls.  The adjusted relative risk (RR) for IBD was 0.99; for ulcerative colitis the RR was 1.1 (confidence intervals 0.44-2.7) and for Crohn’s disease the RR was 0.91 (confidence interval 0.91).  For the meta-analysis which was a secondary part of this study, the RR for IBD with 5 studies was 0.94.

Conclusion: The study results do not suggest an increase risk of IBD with isotretinoin use.

Why did previous studies suggest a link between IBD and isotretinoin? The authors note that this is the first study to adjust for two main confounders, mainly a diagnosis of acne and use of oral tetracycline antibiotics.  Oral antibiotics, including tetracyclines, have been associated with IBD previously.  In addition, the design limits the confounding of contraceptive usage.

Limitations of this study:

  • Only women were studied; however, there are no known biologic factors that would make isotretinoin more problematic for males.
  • Other risk factors were not examined: smoking, ethnicity, diet, IBD family history

Additional references:

  • -Am J Gastroenterol 2009; 104: 2774-78.  Population-based study in Winnipeg, <40yrs.  n=1960 cases and 19,419 controls.  No differences in the proportions of IBD cases taking isotretinoin vs controls.  1.2% of IBD cases received isotretinoin prior to IBD diagnosis (n=25) compared with 1.1% of controls (n=213).  Mean # of days prior to IBD dx was 1102.  Thus, isotretinoin unlikely to be causally-associated with idiopathic IBD.
  • -IBD 2009; 12: Supplement -abstract O -0002  Increased risk of UC after isotretinoin.  OR 4.36 for developing UC
  • -Am J Gastroenterol 2009; 104: 2387-93.  7 country study found no causal association between isotretinoin & colitis.