Effect of mesalazine on mucosal immune biomarkers in irritable bowel syndrome: a randomized controlled proof‐of‐concept study

Abstract

Summary Background Intestinal immune infiltration contributes to symptoms in patients with irritable bowel syndrome (IBS). Aim To assesses the effect of mesalazine (mesalamine) on mucosal immune cells in patients with IBS, through a pilot study. Methods A randomized, double‐blind, placebo‐controlled trial in 20 patients with IBS in tertiary care setting. Patients were randomized to receive placebo or 800 mg mesalazine three times daily for 8 weeks. The primary endpoint was a significant reduction in total colonic immune cells on biopsies obtained at the end of treatment compared to baseline. Secondary endpoints included effects on subsets of immune cells, inflammatory mediators and symptom severity. Intention‐to‐treat analysis was performed. Results Mesalazine markedly reduced immune cells as compared with placebo (P = 0.0082); this effect was ascribed to a marked inhibition of mast cells (P = 0.0014). Mesalazine significantly increased general well‐being (P = 0.038), but had no significant effects on abdominal pain (P = 0.084), bloating (P = 0.177) or bowel habits. No serious drug‐related adverse events were reported during the study. Conclusions Mesalazine is an effective and safe approach to reduce mast cell infiltration and may improve general well‐being in patients with IBS. These results support the hypothesis that immune mechanisms represent potential therapeutic targets in IBS.

Treatment of Diarrhea-Predominant Irritable Bowel Syndrome With Mesalazine and/or Saccharomyces Boulardii

“…The lamina propria, as well as surface and crypt epithelium have been shown to contain increased numbers of T-lymphocytes in IBS; the predominant form of diarrhea in IBS is associated with a greater increase in mucosal T-lymphocytes, relative to the predominant form of constipation (12,16,50,54) . Increased numbers of nerve fibres staining positively for neuron specific enolase, substance P and 5-HT (but not calcitonin gene-related peptide) have been demonstrated in biopsies from the terminal ileum and rectosigmoid in patients with both PI-and non-PI-IBS.…”

Efficacy and mode of action of mesalazine in the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D): a multicentre, parallel-group, randomised placebo-controlled trial

“…There have since been two further reports of open-label treatment 21,22 and two small randomised controlled trials. 23,24 All but the Corinaldesi et al 23 trial used patients with IBS-D. The Bafutto et al trial 22 used mesalazine 800 mg three times a day for 30 days in 61 patients with IBS-D -18 of whom had PI-IBS and showed benefit with a reduction in stool frequency, stool consistency and abdominal pain -but was uncontrolled, with no placebo arm.…”

Medical treatment of colonic diverticular disease: are we sure the aim is right?

“…Therefore, we feel that there is more than a fleeting possibility that the present efforts based on decreasing low grade mucosal inflammation in DD are aimed at a wrong target, i.e., decreasing irritable bowel syndrome-like symptoms [16], especially considering that notwithstanding several studies on the use of mesalazine that are available in the literature, there is still no firm documentation of such an efficacy of the drug in this setting [17].…”