Randomised controlled trial of mesalazine in IBS

Abstract

ObjectiveLow-grade intestinal inflammation plays a role in the pathophysiology of IBS. In this trial, we aimed at evaluating the efficacy and safety of mesalazine in patients with IBS.DesignWe conducted a phase 3, multicentre, tertiary setting, randomised, double-blind, placebo-controlled trial in patients with Rome III confirmed IBS. Patients were randomly assigned to either mesalazine, 800 mg, or placebo, three times daily for 12 weeks, and were followed for additional 12 weeks. The primary efficacy endpoint was satisfactory relief of abdominal pain/discomfort for at least half of the weeks of the treatment period. The key secondary endpoint was satisfactory relief of overall IBS symptoms. Supportive analyses were also performed classifying as responders patients with a percentage of affirmative answers of at least 75% or >75% of time.ResultsA total of 185 patients with IBS were enrolled from 21 centres. For the primary endpoint, the responder patients were 68.6% in the mesalazine group versus 67.4% in the placebo group (p=0.870; 95% CI −12.8 to 15.1). In explorative analyses, with the 75% rule or >75% rule, the percentage of responders was greater in the mesalazine group with a difference over placebo of 11.6% (p=0.115; 95% CI −2.7% to 26.0%) and 5.9% (p=0.404; 95% CI −7.8% to 19.4%), respectively, although these differences were not significant. For the key secondary endpoint, overall symptoms improved in the mesalazine group and reached a significant difference of 15.1% versus placebo (p=0.032; 95% CI 1.5% to 28.7%) with the >75% rule.ConclusionsMesalazine treatment was not superior than placebo on the study primary endpoint. However, a subgroup of patients with IBS showed a sustained therapy response and benefits from a mesalazine therapy.Trial registration numberClincialTrials.gov number, NCT00626288.

The role of mast cells in functional GI disorders

“…In this sense, anti-inflammatory treatment with mesalazine appeared to show improvement in symptom perception in unselected patients with IBS in a small proof-of-concept randomised, double-blind, placebo-controlled trial, in which, in addition, a 36% decrease in MC numbers and a reduction of the number of total immune cells and T cells was observed in the colonic mucosa 108. However, two subsequent large clinical trials differ in the clinical benefit of mesalazine in IBS,109 110 and the effect of mesalazine on MC counts and degranulation was not confirmed 110. Furthermore, there was no effect of mesalazine on 5-HT containing enterochromaffin and CD68 cell numbers, although there was a significant increase in CD3 count in the mesalazine group 110.…”

Therapeutic strategies for functional dyspepsia and irritable bowel syndrome based on pathophysiology

“…In a study evaluating the effects of the mast cell stabilizer ketotifen, this drug reduced visceral hypersensitivity in IBS, and additionally downregulated symptoms, although the symptom response was not conclusive [116]. On the other hand, the anti-inflammatory 5-aminosalasylic acid drug mesalazine was not superior to placebo in IBS, although a small subgroup of patients may improve [117]. There have been no trials of targeted treatments for eosinophil downregulation in IBS.…”

Modern Management of Irritable Bowel Syndrome: More Than Motility

“…In a preliminary report of a follow-up study, the histamine 1 -receptor antagonist ebastine significantly decreased abdominal pain over the course of 12 weeks controlled trial [67]. Based on the potential role of inflammatory cells, the anti-inflammatory agent mesalazine has been evaluated in IBS in a number of moderate-sized controlled trials, with variable and largely negative results [68,69,70]. …”