CHICAGO – Treating diarrhea-predominant irritable bowel syndrome with mesalazine for 12 weeks failed to improve stool frequency or other symptoms, compared with placebo, in a multicenter, randomized double-blind trial with 115 patients.
Stool frequency decreased in both groups from a mean of four bowel movements per day to three per day by weeks 11 and 12. Mesalazine (also known as mesalamine or 5-aminosalicylic acid) also produced no significant differences, compared with placebo, in secondary outcomes, including abdominal pain scores, stool consistency, satisfactory relief of symptoms of irritable bowel syndrome (IBS), anxiety, depression, or Patient Health Questionnaire–12 Somatic Symptoms scores, Dr. Ching Lam reported at the annual Digestive Disease Week.
Dr. Ching Lam
Patients took 2 g/day of mesalazine or placebo for 1 week and then increased the dose to 2 g b.i.d. if they could tolerate it.
All were adults with diarrhea-predominant IBD who had completed a prerandomization 2-week stool diary showing a stool frequency of at least three per day for more than 2 days per week and a stool consistency of at least 25% type 5-7 and less than 25% type 1-2 on the Bristol Stool Form Scale. All underwent a baseline colonoscopy/sigmoidoscopy before randomization to exclude patients with microscopic or inflammatory colitis. The study also excluded patients who were taking NSAIDs or other drugs that affect gut motility and patients with a history of abdominal surgery or renal or liver impairment.
The study initially randomized 136 patients, but 11 in the mesalazine group and 10 on placebo were excluded from the intent-to-treat analysis of results because they withdrew consent, were lost to follow-up, or had an incomplete stool diary at weeks 11-12, or because results were not available due to adverse events, said Dr. Lam of Nottingham (England) University.
Clinicians had been interested in mesalazine for diarrhea-predominant IBS because small randomized, controlled pilot studies and some open-label studies had suggested that the drug might improve IBS symptoms of abdominal pain and stool frequency and consistency, especially in patients with postinfectious IBS. The drug is approved to treat ulcerative colitis and some other bowel diseases.
Those earlier studies also suggested that mesalazine might reduce the numbers of mast cells in unselected cohorts of patients with IBS. In the current study, a subgroup of patients did show elevations in "mast cell percent area stained," and this correlated weakly with urgency and stool consistency, but mesalazine treatment did not reduce the mast cell percent area stained, Dr. Lam reported.
An analysis of results for a small subgroup of patients with postinfectious IBS suggested that mesalazine may benefit them, "but this requires a larger, adequately powered study to confirm," she said. Better phenotyping of the heterogeneous group of patients with IBS and diarrhea would help evaluate any new treatments, she added.
British government agencies funded the trial. Several of Dr. Lam’s coinvestigators reported financial associations with multiple pharmaceutical companies.
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