NEW ORLEANS – The numbers can be daunting: juries awarding more than $56 million to patients so far, approximately 1,000 federal and state lawsuits pending, and an excess of 2,500 individuals filing claims in New Jersey State courts alone.
Add to that frequent TV ads from attorneys about inflammatory bowel disease risk with isotretinoin, and you’re bound to encounter fear and confusion from your teenage patients and their parents when you suggest this acne-fighting agent.
"Patients have the idea that this drug is just no longer available because it’s too dangerous," Dr. Julie Harper said at this year’s annual meeting of the American Academy of Dermatology. "It is still out there, as we all know."
So how do you counsel patients in this climate of fear? Dr. Harper counters with some numbers of her own. "This is a real risk in a small percentage of patients, probably occurring at a rate of 1 per 10,000. This is what I tell my patients," said Dr. Harper, a dermatologist in private practice in Birmingham, Ala.
Dr. Harper estimated writing more than 1,000 isotretinoin prescriptions during her dermatology career. "So it’s possible I may never reach 10,000 prescriptions and see this adverse event, but it’s possible."
Isotretinoin is not the only acne fighter implicated in risk for inflammatory bowel disease (IBD), Dr. Harper said. Patients taking tetracyclines, doxycycline in particular, were more likely to develop IBD in a retrospective study of 94,487 individuals with acne (Am. J. Gastroenterol. 2010;105:2610-16). This report generated a lot of attention at the AAD meeting.
"Keep this in mind when we consider isotretinoin and IBD," Dr. Harper said. "There can be a confounding factor."
Dr. Harper highlighted the salient studies from the gastroenterology researchers who assessed a link between isotretinoin and IBD. It all started with a first case report (Gastroenterology. 1987;93:606-9)."It was a suggestive case, but had an ‘n’ of one."
Almost 20 years later came a review article. Researchers identified 85 reports of IBD signs/symptoms associated with isotretinoin in the U.S. Food and Drug Administration MedWatch database between 1997 and 2002 (Am. J. Gastroenterol. 2006:101:1569-73). They also reviewed clinical trial data from isotretinoin manufacturer Hoffman-LaRoche for any de novo cases of IBD not reported to the FDA. "There were none," Dr. Harper said.
The investigators scored the MedWatch reports for strength of causation. Of the 85 reports, 4 were in the "highly probable" range; 58 were in the "probable" range; 23 were "possible," and zero were "doubtful." Three of these reported cases included documented improvement when isotretinoin was withdrawn, and worsening when isotretinoin was reintroduced, Dr. Harper said.
Researchers Dr. Seth D. Crockett and associates reviewed 12 case reports and one case series published in the literature and determined there was insufficient evidence to support or refute a casual relationship between isotretinoin and IBD (Am. J. Gastroenterol. 2009;104:2387-93).
"But we’re seeing what the juries are awarding, so there is a disconnect there," Dr. Harper said.
The following year, the same lead researcher and his associates reported their own case-control study (Am. J. Gastroenterol. 2010;105:1986-93). They assessed an insurance company database with 8,189 people with IBD (3,664 with Crohn’s disease, 4,428 with ulcerative colitis, and 97 with unspecified IBD) and 21,832 controls. They identified 60 people (24 cases, 36 controls) who had exposure to isotretinoin.
"That is not to say it’s not real, but we’re talking big denominators and a low number of cases," Dr. Harper said.
Interestingly, Dr. Crockett’s research team did not find an association between isotretinoin exposure and Crohn’s disease (odds ratio, 0.68) but reported a positive association with ulcerative colitis (OR, 4.36).
During the question-and-answer period, Dr. Bruce Thiers, a meeting attendee who has been working on behalf of Hoffman-La Roche on the lawsuits, commented on the risk. "If you look at the incidence of IBD, the highest incidence is in teenagers and adults. You are treating the age group that gets IBD.
"Right now if you watch television more than 10 minutes you see an advertisement," Dr. Thiers said. "Roche is being sued for people who developed IBD 6 months to 2 years [after isotretinoin]. Some had symptomatology beforehand, so it could also be the drug suppressed the disease and then it recurred." Dr. Thiers is professor and chair of dermatology at the Medical University of South Carolina in Charleston.
"We don’t have hard, fast information on a lot of what we prescribe," Dr. James Q. Del Rosso, a private practice dermatologist in Las Vegas, said before starting his subsequent presentation at the meeting."There is really nothing we can prescribe that has no risk, and patients have to accept some risk. I tell patients that there is always a chance you can get something very rare [but] that is very unlikely. I cannot reassure you that will not happen, but I can tell you the majority of people do very well."