The acne drug isotretinoin doesn't boost risk of inflammatory bowel disease (IBD), a large observational study in young women affirmed.
Women of reproductive age taking the vitamin A derivative had a nearly identical risk of IBD as those not exposed, with an adjusted relative risk of 0.99 (95% CI 0.52 to 1.90), Mahyar Etminan, PharmD, MSc, of the University of British Columbia in Vancouver, and colleagues found.
Pooling their results with the four other studies done to date likewise supported no elevated risk of IBD, or Crohn's disease or ulcerative colitis individually, they reported in the February issue of JAMA Dermatology, suggesting that the results would generalize across the sexes.
"Because inflammatory acne in children and adolescents carries a high psychological burden, clinicians should not be discouraged from prescribing this drug owing to a putative association with IBD," the group urged.
Isotretinoin has been plagued by personal injury claims since case reports suggested an IBD risk. Drugmaker Roche pulled its Accutane brand off the market after paying out millions, although generic isotretinoin remains on the market.
The lawsuits have made dermatologists skittish, an editorial accompanying the study acknowledged, although the editorialists agreed that the drug shouldn't be withheld from patients who need it.
"Dermatologists should counsel patients that the possibility of an association of isotretinoin use and IBD has been raised but not proved by the best available evidence," recommended Catalin Mihai Popescu, MD, PhD, of Colentina Hospital in Bucharest, Romania, and Michael Bigby, MD, of Harvard and Beth Israel Deaconess Medical Center in Boston.
The best evidence for a risk came from a large population-based case-control study, which turned up a nonsignificant relative risk of 1.68 for IBD overall with isotretinoin but a strong association with ulcerative colitis specifically (RR 4.36, 95% CI 1.97 to 9.66).
Because that study didn't adjust for severity of acne or tetracycline antibiotic use as possible confounding factors, Etminan's group reanalyzed the same database with a nested case-control design that allowed for adjustment for those confounders.
The reanalysis also tackled confounding by combined oral contraceptive use, which is commonly associated with isotretinoin use in women (prescription requires documentation of two forms of contraception due to known fetal toxic effects) and is also considered a possible risk factor for IBD.
The researchers included 2,159 IBD cases matched with 43,180 controls among women ages 18 to 46 who had been prescribed oral contraception as recorded in the medical and pharmacy IMS LifeLink claims database, which pools data from 102 U.S. health plans.
Among these, only 10 IBD patients and 191 controls had taken isotretinoin (0.46% and 0.44%, respectively).
Similar to the prior analysis, isotretinoin showed no link to Crohn's disease specifically (adjusted RR 0.91, 95% CI 0.37 to 2.25).
This time, though, the drug showed no strong or significant association with ulcerative colitis either (adjusted RR 1.10, 95% CI 0.44 to 2.70).
Longer duration of isotretinoin use didn't appear to increase the IBD risk.
Meta-analysis with three published and one unpublished study suggested a similar pattern, without a significantly elevated risk of either ulcerative colitis (RR 1.61, 95% CI 0.88 to 2.95) or Crohn's disease (RR 0.75, 95% CI 0.46 to 1.24) or IBD overall (pooled RR 0.94, 95% CI 0.65 to 1.36).
Even in the worst-case scenario using the highest upper 95% confidence interval and assuming an ulcerative colitis incidence of 10 per 100,000 person-years, the number needed to harm would be 5,130 with an absolute risk difference of 0.019%, Popescu and Bigby noted.
Although the design of the study meant it would generalize only to women taking oral combined contraceptives, the researchers and editorialists alike pointed out that there's no reason to expect that the results would differ for men or any other population.
Another limitation was the inability to control for all IBD risk factors, such as smoking, diet, and family history, although confounding wasn't likely to be strong for most "because clinicians are unlikely to prescribe isotretinoin differentially to their patients on the basis of ethnicity, smoking, or diet."
The researchers reported having no conflicts of interest to disclose aside from one of the authors being employed by the FDA.
Popescu and Bigby reported having no conflicts of interest to disclose.
JAMA DermatologySource Reference: Popescu CM, Bigby M "The weight of evidence on the association of isotretinoin use and the development of inflammatory bowel disease" JAMA Dermatol 2013; 149: 221-222.