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Posted by on Aug 3, 2010 in Epidemiology, Pharma

Link Between Accutane and Inflammatory Bowel Disease Probably Idiosyncratic

Link Between Accutane and Inflammatory Bowel Disease Probably Idiosyncratic

Roaccutane.jpg

But try explaining that concept to a jury.

The clinical data, and they are imperfect to say the least, suggest that there may be an idiosyncratic link between Accutane use and depression or suicide. But studies (not case reports) do not collectively support a bona fide association between the drug and affective disorders in users.*

It turns out that the same may be true for any posited association between Accutane and inflammatory bowel disease (IBD)despite the hundreds of personal-injury cases brought against Accutane’s former maker, Roche, in mass-tort litigation.**

There are at least 3 compelling case reports (here, here, and here) suggesting that Accutane causes or exacerbates enteritis or colitis and that these flares remit and recur with withdrawal and reuse, respectively, of the drug. And the drug’s PI warns against the occurrence of IBD with Accutane use. (The mechanism by which Accutane, a vitamin A analogue, might cause IBD is unknown.) But a recent, population-based study in Canada found no association between Accutane use and the development of IBD. The study, which was not funded by Roche, is evidently the first of its kind to examine any such association, outside of case reports.

By using the Manitoba Health databases, the Canadian authors identified a similar percentage of patients (age cutoff, <40 years) who used Accutane before or after their first diagnosis of IBD (see adapted Table). These data suggest no association, much less a causal link, between Accutane use and the development of IBD. Moreover, Accutane use among matched controls (for age, sex, and residence) without IBD was similar (1.1% and 0.9% for the before and after populations, respectively). And the mean time between the diagnosis of IBD and the last Accutane prescription was lengthy (1048 days or ~2.8 years), suggesting that any cause-effect relationship in the 25 “before” IBD cases is unlikely.

Accutane Use

Cases
(%)

Matched Controls
(%)

Odds Ratio
(95% CI)

IBD

   Before dx

25 (1.2)

213 (1.1)

1.16 (0.73, 1.77)

   After dx

23 (1.2)

182 (0.9)

1.25 (0.77, 1.94)

   None

1960 (97.6)

19,419 (98.0)

 

Crohn’s

   Before dx

14 (1.3)

120 (1.1)

1.15 (0.61, 2.02)

   After dx

14 (1.3)

115 (1.0)

1.21 (0.64, 2.12)

   None

1090 (97.5)

10,801 (97.9)

 

Ulcerative colitis (UC)

   Before dx

11 (1.2)

93 (1.1)

1.16 (0.56, 2.20)

   After dx

9 (1.0)

67 (0.8)

1.33 (0.58, 2.69)

   None

870 (97.8)

8618 (98.2)

 

A more recently published, case-control study from UNC largely confirmed the Canadian findings, but the US authors concluded a “strong” association between Accutane use and UC among 24 total cases of IBD (OR for ulcerative colitis = 4.36 [95% CI: 1.97, 9.66]). The risk of UC appeared to increase with Accutane dosage and duration of treatment among the small number of cases (only 0.3% of subjects in the total IBD population had been exposed to Accutane). The US authors concluded, “Although the absolute risk of developing UC after taking [Accutane] is likely quite small, clinicians prescribing [Accutane] as well as prospective patients should be aware of this possible association.” 

* Whatever Emory psychiatrist Doug Bremner may say on YouTube in his not-particularly-sophisticated interpretation of his and others’ data.

** One of these cases was brought by actor James Marshall of “Twin Peaks” and A Few Good Men fame. Marshall, who is reportedly corralling celebrity witnesses to argue his case, claims that Accutane caused his IBD, which in turn put the kibosh on what would have been a James Dean-like film career (without the violent, early death, presumably). See last week’s Bloomberg story.

Photo of Roaccutane, aka Accutane, from Wikipedia.

08/06/10 addendum: Yesterday the New Jersey Superior Court Appellate Division repealed the $10.5 million verdict for the plaintiff in Kendall v Hoffman-La Roche. The appellate court ruled that the Roche was hobbled during trial by restrictions on the presentation of background data for the incidence of IBD. Kendall, who was treated several times with Accutane for nodular acne during adolescence and young adulthood, developed UC at the age of 15 years, which coincided with Accutane retreatment. However, her bowel condition was not uniformly exacerbated by further treatments with Accutane.

Kendall’s case hinges on the argument that Roche failed to warn of the risk of IBD, and Roche’s warnings are based on risk data known at the time of Kendall’s Accutane treatments. Bloomberg covered the story; the appellate decision can be found here.

A similar appellate reversal was made in McCarrell v Hoffman LaRoche, and the retrial resulted in an even bigger verdict for the plaintiff. An appeal on this verdict is reportedly in the works.

bmartin (1127 Posts)

A native East Tennessean, Barbara Martin is a formerly practicing, board-certified neurologist who received her BS (psychology, summa cum laude) and MD from Duke University before completing her postgraduate training (internship, residency, fellowship) at the Hospital of the University of Pennsylvania in Philadelphia. She has worked in academia, private practice, medical publishing, drug market research, and continuing medical education (CME). For the last 3 years, she has worked in a freelance capacity as a medical writer, analyst, and consultant. Follow Dr. Barbara Martin on and Twitter.