Medication Seen to Help Prevent Post-Surgery Relapse in Crohn’s Patients Who Smoke

Medication Seen to Help Prevent Post-Surgery Relapse in Crohn’s Patients Who Smoke

Smoking long has been associated with an increased relapse risk for patients with Crohn’s disease. But results of a new trial indicate that the immunosupressive medication mercaptopurine (Purinethol)  has a greater effect on patients who continue to smoke after having intestinal resection surgery.

The benefit of the drug in preventing relapses was negligible in nonsmokers, who probably could be managed by close monitoring without the need for drug therapy.

Results of the study are published in Lancet Gastroenterology and Hepatology, in a article titled Mercaptopurine versus placebo to prevent recurrence of Crohn’s disease after surgical resection (TOPPIC): a multicentre, double-blind, randomised controlled trial.”

Estimates vary regarding the frequency of surgical resection in Crohn’s disease, a chronic, relapsing inflammatory bowel disease. Historical data suggest that up to 60% of patients need a major abdominal resection within 10 years of diagnosis. Purinethol is an immunosuppressive medication used to treat Crohn’s and ulcerative colitis.

“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 news release. “Our study confirms that the most important thing somebody with Crohn’s disease can do for their health is not to smoke.”

To investigate whether mercaptopurine can prevent or delay postoperative clinical recurrence of Crohn’s disease, Satsangi and colleagues conducted a randomised, placebo-controlled, double-blind trial at 29 U.K. secondary and tertiary hospitals of patients (older than 16 years in Scotland or older than 18 in England and Wales) with Crohn’s disease who had undergone intestinal resection.

A total of 240 patients with Crohn’s disease were randomized to either 1mg/kg daily of mercaptopurine (128 patients), or to a placebo (112 patients). Sixty-one percent of the patients were women and 23% were smokers.

At three years of follow-up, 16 (13%) of patients in the mercaptopurine group versus 26 (23%) patients in the placebo group had a clinical recurrence of Crohn’s disease and needed anti-inflammatory rescue treatment or primary surgical intervention.

Among smokers, 10 percent in the mercaptopurine group relapsed compared with 46% of the placebo group. Among nonsmokers, 13% versus 16% relapsed, respectively.

In a subgroup analysis, the researchers found there were no differences in mercaptopurine versus placebo among patients with previous exposure to thiopurines, infliximab or methotrexate or previous surgery. There was no significant impact on the effect of mercaptopurine versus placebo regarding the variables of duration of disease, or age at diagnosis.

“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. “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.”