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TOPPIC: Smoking increases postoperative relapse risk in Crohn's disease
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Mercaptopurine prevented recurrence of Crohn’s disease only in patients who continued to smoke after intestinal resection surgery, according to data from the TOPPIC trial recently published in Lancet Gastroenterology and Hepatology.
Moreover, the data confirmed that smoking is strongly associated with postoperative disease relapse, leading researchers to emphasize the importance of smoking cessation in these patients.
Jack Satsangi
“There is an unmet need to identify therapies or lifestyle changes that prevent Crohn’s disease recurrence after surgery to avoid patients having to undergo multiple operations,” Jack Satsangi, DPhil, of the gastrointestinal unit in the Center of Genomics and Experimental Medicine at the University of Edinburgh, and consultant physician at the Western General Hospital in the U.K., said in a press release. “Our study confirms that the most important thing somebody with Crohn’s disease can do for their health is not to smoke.”
To determine whether mercaptopurine can prevent postoperative clinical recurrence of Crohn’s disease, Satsangi and colleagues performed a randomized, placebo-controlled, double blind trial in Crohn’s patients who underwent intestinal resection at 29 hospitals in the U.K. between June 2008 and April 2012. All 240 patients were aged at least 16 years, 61% were women and 23% were smokers.
The researchers randomly assigned 128 patients to receive 1 mg/kg oral mercaptopurine daily and 112 to placebo.
After 3 years of follow-up, 13% of the mercaptopurine group relapsed and needed anti-inflammatory rescue treatment or primary surgical intervention vs. 23% of the placebo group (adjusted HR = 0.54; 95% CI, 0.27-1.06; P = .07).
Among smokers, 10% in the mercaptopurine group relapsed compared with 46% of the placebo group (HR = 0.13; 95% CI, 0.04-0.46), and among nonsmokers, 13% vs. 16% relapsed (HR = 0.9; 95% CI, 0.42-1.94; P for interaction = .018).
Subgroup analyses showed no significant difference in mercaptopurine vs. placebo among patients with previous exposure to thiopurines, infliximab or methotrexate or previous surgery. Duration of disease or age at diagnosis also had no significant impact on the effect of mercaptopurine vs. placebo.
Adverse events were comparable between groups, causing discontinuation of treatment in 30% of the mercaptopurine group and 37% of the placebo group.
“People who are unable to quit smoking are at high risk of relapse after surgery and may begin treatment with thiopurines immediately after their operation,” Satsangi said in the press release. “For non-smokers, however, we found that thiopurines offer little benefit at preventing relapse after surgery. For these patients, close monitoring in the first year is the best course of action, rather than immediate drug therapy.” – by Adam Leitenberger
Disclosures: The researchers report no relevant financial disclosures.
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