Mercaptopurine prevents postop clinical recurrence of Crohn's disease in smokers

Last Updated: 2016-09-13

By Will Boggs MD

NEW YORK (Reuters Health) - Mercaptopurine prevents clinical recurrence of Crohn's disease after surgical resection, but only in smokers, according to results from the multicenter TOPPIC trial.

"The effect of thiopurines in postoperative prophylaxis is most evident in smokers," Dr. Jack Satsangi from Western General Hospital in Edinburgh, U.K., told Reuters Health by email. "Smoking is the key clinical factor predictive of postoperative recurrence."

Recurrence is common in the first two years after surgery, but there is a paucity of evidence to support any drug treatment strategy to prevent or delay postoperative recurrence of Crohn's disease.

In a placebo-controlled randomized trial including 240 patients, Dr. Satsangi and colleagues from 29 U.K. hospitals tested whether mercaptopurine could prevent or delay postoperative clinical recurrence of Crohn's disease requiring anti-inflammatory rescue treatment or surgery.

During a median follow-up of 36 months, the primary endpoint of clinical recurrence of Crohn's disease and the need for anti-inflammatory rescue treatment or primary surgical intervention occurred in 13% of the mercaptopurine group versus 23% of the placebo group (p=0.07).

In subgroup analyses, mercaptopurine significantly reduced recurrence only in smokers. The number needed to treat (NNT) to avoid one clinical recurrence was three for smokers.

Complete endoscopic remission was maintained in proportionately more patients on mercaptopurine than placebo at both week 49 and week 157.

The fecal calprotectin level proved to be an unreliable predictor of recurrence and remission, the researchers found.

Almost one-third of patients in the mercaptopurine group (30%) and even more in the placebo group (37%) discontinued treatment as a result of adverse events, the team reports in The Lancet Gastroenterology and Hepatology, online August 30.

Dr. Satsangi expressed surprise "that the benefit of mercaptopurine is so evident in smokers and so weak in non-smokers," and suggested "a renewed focus on smoking cessation."

Dr. Giovanni C. Actis from Gradenigo Hospital in Turin, Italy, who has studied numerous treatments for inflammatory bowel disease (IBD) but was not involved in the new work, told Reuters Health by email, "The placebo group had a high frequency of side effects, blurring the data in the treatment group."

"At any rate, the results remind us that in the era of biologics, IBD questions are still played on cheap fundamentals: thiopurines and smoking," Dr. Actis said.

The trial did not have commercial funding.

SOURCE: http://bit.ly/2cAYQcw

Lancet Gastroenterol Hepatol 2016.