Gastroenterologist – and blogger – Michael Kirsch – brought the following two facts to my attention.
In New Jersey, a jury awarded $18 million to two plaintiffs for damages related to the drug Accutane (isotretinoin). Was it because of the teratogenic effects of the medication on the unborn – a well described effect? No. The plaintiffs developed colitis – and they alleged Roche, the manufacturer, failed to warn them of the risk.
The second fact: There are over 7,000 cases against Roche propelling the same “failure to warn” allegation. Roche has already paid out $80 million in verdicts and it still denies the medication causes colitis. In 2009, Roche removed Accutane from the market. Generic alternatives exist. Their manufacturers have not been spared litigation.
Here’s what the American Journal of Gastroenterology said about the matter in 2010, after Roche withdrew from the market. (Crockett SD, et al. Isotretinoin use and the risk of inflammatory bowel disease: a case-control study. Am J Gastroenterology. 2010 Sep;105(9):1986-93.)
“Ulcerative colitis but not Crohn’s disease is associated with previous isotretinoin exposure. Higher dose of isotretinoin seems to augment this risk. Although the absolute risk of developing ulcerative colitis after taking isotretinoin is likely quite small, clinicians prescribing isotretinoin as well as prospective patients should be aware of this possible association.”
And in 2012, hot off the press – a 12 year retrospective study. Alhusayen RO, et al. Isotretinoin use and the risk of inflammatory bowel disease: A population-based cohort study. J Invest Dermatol. 2012 Oct 25. doi: 10.1038/jid.2012.387. [Epub ahead of print].
Our primary analyses found no association between isotretinoin and inflammatory bowel disease (IBD). In prespecified secondary analyses, some evidence was found of associations with isotretinoin as well as topical acne medications, suggesting a possible association between IBD and acne itself. Additional research is needed to explore this possibility.
In other words, acne may be associated with inflammatory bowel disease – and Accutane’s association, if present, may not be causal.
To be fair: The FDA label for Accutane in 2002 included the following warning:
Inflammatory Bowel Disease: Accutane has been associated with inflammatory bowel disease (including regional ileitis) in patients without a prior history of intestinal disorders. In some instances, symptoms have been reported to persist after Accutane treatment has been stopped. Patients experiencing abdominal pain, rectal bleeding or severe diarrhea should discontinue Accutane immediately.
Accutane was marketed for severe recalcitrant nodular acne – not run of the mill pimples. For those afflicted with the recalcitrant variety, Accutane was a godsend. Its side effect profile was long: teratogenic – and absolutely contraindicated in patients who were pregnant or likely to become pregnant; depression; pseudotumor cerebri, pancreatitis, and more. So, definitely a tradeoff.
The question, as with all pharmaceuticals, is whether the perceived benefit outweighs the risk. We are explained risk in a statistical sense. “Ms. Jones, there’s a 3% risk of infection with this surgery.” We experience risk in a binary sense. “Ms. Jones, you have a post-op infection.”
The question: if a patient accepts the discussed risks of suicidal depression, pseudotumor cerebri, and pancreatitis – but there’s no discussion of the small risk of inflammatory bowel disease….. would that patient opt against Accutane to treat recurrent, pustular acne? Unlikely. The collection of plaintiffs is arguing otherwise. And the data from most recent gastroenterology journals suggests the early associations of Accutane and inflammatory bowel disease are either small or non-causal.
Somewhere between many and most patients want physicians to tell them what to do. If I tell a patient about a potential treatment and its risks, the usual answer I get begins with “well, if I’ve got to have it done….” Myself, I don’t let them off that easily. I have a standard reply, which begins with, “No, you don’t have to have anything done. The only two certainties in life are death and taxes. Literally everything else is optional.”
And then I describe the risks again and paint the picture of what’s likely if they have treatment and what is likely if they don’t. I also–always–paint the picture of the unlikely outcomes: “if you ~don’t~ have treatment, you might end up dying of old age without ever having a problem from this disease. You have to be the one to decide whether you want to take the risks associated with the treatment. No one else can make that call for you.”
Unruptured aneurysms are the classic here: Mayo published a very strange article in the late 90’s about likelihoods of aneurysm rupture, essentially arguing that aneurysms smaller than 1 cm were so unlikely to rupture that any treatment involving a risk greater than about 3% were contraindicated. No known treatment has that low a risk–no honest surgeon would tell a patient that his surgical risk was that low for a craniotomy and aneurysm clipping, and no honest interventionalist would either.
I’m not sure how many people died because of that article, but the quoted risk of rupture was ~ 0.05% / year. As people pointed out, since we know the absolute number of aneurysmal subarachnoid hemorrhage) SAH in the US–about 30,000/year–if the real rate were as stated, that means that we know the prevalence of intracranial aneurysm. It would have been about 35% of the US population. Autopsy prevalence studies vary, but even the most liberal “swinging chad” criterion makes it about 1.5%–over an order of magnitude lower than was found. In other words, treatment is indicated at far higher risk levels.
Needless to say, the downside risk of an aneurysm rupturing–35-50% DOA rate–is pretty different from that of acne or any kind. But so are the risks of treatment. About the only time I encourage a patient to have treatment is when a bleed has already occurred: the rebleed rate is so high–about 2%/day for the first couple weeks–that leaving one alone is a singularly bad idea.
Bottom line: nothing in medicine is black and white, and unless a patient lacks the capacity to understand that, I don’t make decisions for him.