Mesalamine failed to prevent diverticulitis recurrence

Mesalamine was not effective in the prevention of recurrent diverticulitis compared with placebo, according to results from two phase 3 clinical trials.

“Previous studies have suggested that mesalamine could be beneficial in preventing recurrent diverticulitis,” Jeffrey B. Raskin, MD, University of Miami Miller School of Medicine, told Healio.com/Gastroenterology. “This large, controlled study was needed to further define a potential role for mesalamine in diverticulosis (quality of life) and preventing recurrent diverticulitis. The results were conclusive that mesalamine was no better than placebo in preventing recurrent diverticulitis or any improvement in quality of life issues over the course of the study.”

To ascertain the efficacy and safety of multimatrix mesalamine in preventing recurrent acute diverticulitis, Raskin and colleagues conducted the identical, multinational, placebo-controlled PREVENT1 (n=590) and PREVENT2 (n=592) trials from November 2007 to March 2012 and December 2007 to November 2011, respectively. All participants had at least one episode of acute diverticulitis within the 2 years before enrollment that resolved without surgery and were randomly grouped to 1.2 g, 2.4 g or 4.8 g of mesalamine or placebo once daily for 104 weeks. Patients had 14 follow-up visits throughout the study period, and those with disease symptoms underwent abdominal CT scan.

At week 104, none of the three dose groups demonstrated a positive effect on the rate of recurrence associated with mesalamine, with 52.7% of the PREVENT1 highest dose mesalamine group remaining recurrence-free vs. 64.6% with placebo (P=.047) and 69.1% vs. 67.6% in PREVENT2 (P=.778). Mesalamine did not reduce time to recurrence or need for surgery, and the safety profile was consistent with previous observations with all doses well tolerated.

“Mesalamine did not prevent recurrence of diverticulitis compared with placebo; results were robust, with no therapeutic effect of mesalamine evidence using diverticulitis recurrence and across all sensitivity analyses performed to account for dropouts,” the researchers wrote.

In an accompanying editorial, experts theorized why a drug effective in treating and preventing a disease cannot prevent its recurrence.

Antonio Tursi

Silvio Danese

“The question of why mesalamine seems to be effective in treating [symptomatic uncomplicated diverticular disease] and in preventing diverticulitis occurrence, but not in preventing diverticulitis recurrence, remains,” wrote Antonio Tursi, MD, ASL BAT, and Silvio Danese, MD, PhD, IBD Center at Humanitas Clinical and Research Hospital, Italy. “We can speculate that, if the patients are at the first episode of diverticulitis, it is probable that the disease still has lower levels of fibrosis and greater inflammation: In those patients, mesalamine is still able to control inflammation and therefore symptoms and recurrence of the disease. On the contrary, >2 attacks are able to cause fibrosis, limiting the mesalamine absorption across the colonic wall, and therefore mesalamine is ineffective.”

For more information:

Raskin JB. Gastroenterology. 2014;147:793-802.

Tursi A. Gastroenterology. 2014;147:733-736.

Disclosure: See the study for a full list of relevant financial disclosures.