WAIKOLOA, HAWAII — Two studies—both conducted by gastroenterologists—refute the notion that isotretinoin causes inflammatory bowel disease.

Neither found a basis for allegations of an increased risk of IBD in patients who were treated with isotretinoin. “You can't say anything with certainty in life, but at least thus far the data we have are very reassuring that there is no association,” Dr. Sheila Fallon Friedlander said at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation.

She cited a retrospective, nested case-control study by investigators at the University of Manitoba, Winnipeg, who used the comprehensive provincial IBD database to demonstrate that patients with IBD were no more likely to have used isotretinoin before diagnosis than were matched controls, the investigators concluded (Am. J. Gastroenterol. 2009;104:2774–8).

Dr. J. Mark Jackson of the University of Louisville (Ky.) characterized the Manitoba study as “a really well-done study coming at a critical time,” conducted by physicians who deal with IBD and, therefore, have no stake in protecting a drug that could cause it.

The second study was a seven-country, systematic data search led by gastroenterologists at the University of North Carolina at Chapel Hill. Unlike the earlier study, this analysis used the rigorous Chapel Hill criteria designed to weigh the strength, consistency, specificity, and plausibility of scientific evidence, and on that basis, the investigators determined no causal association had been established (Am. J. Gastroenterol. 2009;104:2387–93).

“We now have some very good data reviews showing that IBD is not overrepresented in patients who use isotretinoin,” Dr. Jackson said in an interview. “When this issue comes up [in prescribing], we need to make people aware that this rumor has not been validated.”

Personal injury lawyers seized on an earlier study that concluded it was “highly probable” that isotretinoin was the cause of four cases of IBD reported to the Food and Drug Administration's MedWatch program, with the oral retinoid being deemed the “probable” cause of another 58 (Am. J. Gastroenterol. 2006;101:1569–73). Trial investigator Dr. Sunanda Kane of the University of Chicago was contacted for an interview, but was unable to comment because of pending litigation. The other three study investigators never responded to interview requests.

“This is a situation where there are conflicting data, but a bottom line of interest to all of us is that a New Jersey jury has awarded $12.9 million to patients who've taken isotretinoin and developed IBD,” said Dr. Friedlander, a dermatologist who is a clinical professor of pediatrics and medicine at the University of California, San Diego.

Lawyers shooting for claims have found isotretinoin to be an easy mark for years. The finding that it could increase birth defects by up to 30% left it “an open target,” Dr. Jackson said. “It's always been on the legal radar because of this past issue, and it tends to get put back in the forefront frequently—it's an easy medicine to beat up.” He said he makes it a practice to discuss reports of these issues with patients before prescribing isotretinoin. “I bring it up with my patients because I don't want them hearing it from some other source first,” he said.

At the meeting, when Dr. Jackson asked how many audience members have fielded questions from their patients regarding a putative isotretinoin-IBD link, the majority of dermatologists' hands shot up.

Dr. Seth D. Crockett, a coauthor of the University of North Carolina study, tried to bring some perspective to the issue in an interview with this news organization. “Our study was a critical appraisal of the literature and an assessment of causality. Basically we found that the only published evidence is case reports, which generally is considered poor evidence to establish causality. The best evidence is from epidemiologic studies such as the University of Manitoba study,” he said.

“It's important to recognize that the absence of published evidence does not mean the absence of an association; it just means that there's insufficient evidence in the scientific literature thus far to support a causal connection between isotretinoin and IBD,” added Dr. Crockett of the division of gastroenterology and hepatology at the University of North Carolina at Chapel Hill.

Isotretinoin is now available only in generic form.

Disclosures: Dr. Jackson and Dr. Friedlander indicated that they are long-time prescribers of isotretinoin in severe cases of acne. Dr. Jackson has received support from Roche Pharmaceuticals (manufacturer of Accutane). Dr. Crockett had no relevant conflicts of interest. SDEF and this news organization are owned by Elsevier.

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Dr. J. Mark Jackson talks with patients before he prescribes isotretinoin.

Source © Tom Fougerousse/University of Louisville

Isotretinoin-IBD Connection Is Unsupported