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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

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
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
Background

Diarrhoea-predominant irritable bowel syndrome (IBS-D) is a common outcome after inflammation due to bacterial gastroenteritis. Several studies have shown ongoing immune activation in the mucosa of patients with IBS-D and a number of studies have suggested that mesalazine slow-release granule formulation (2?g; PENTASA®, Ferring Pharmaceuticals Ltd) may provide benefit including a reduction in stool frequency.

Objectives

Our primary aim was to compare the effect of mesalazine with placebo on stool frequency. Our secondary aims were to assess the effect of mesalazine on abdominal pain, stool consistency, urgency and satisfactory relief of irritable bowel syndrome (IBS) symptoms.

Design/participants/intervention

We performed a double-blind, randomised placebo-controlled trial of 2?g mesalazine twice daily compared with placebo for 3 months in Rome III criteria patients with IBS-D.

Settings

Participants were recruited from the primary care research network and secondary care hospitals. Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of ‘satisfactory relief of IBS symptoms’. Those recruited in Nottingham had sigmoid biopsies and/or magnetic resonance imaging of the abdomen at the start and end of the trial.

Results

A total of 136 patients with IBS-D (82 female, 54 male) were randomised; 10 patients withdrew from each group. Analysis by intention to treat showed that the mean daily average stool frequency during weeks 11 and 12 was 2.8 [standard deviation (SD) 1.2] in the mesalazine group and 2.7 (SD 1.9) in the placebo group, with a group difference of 0.1 (95% confidence interval –0.33 to 0.53); p?=?0.66.

Conclusions

Mesalazine did not improve abdominal pain, stool consistency or percentage with satisfactory relief compared with placebo during the last 2 weeks’ follow-up. A post hoc analysis in 13 postinfectious patients with IBS appeared to show benefit but this needs confirmation in a larger group. More precise subtyping based on underlying disease mechanisms may allow more effective targeting of treatment in IBS.

Trial registration

Current Controlled Trials ISRCTN76612274.

Funding

This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership.
2050-4365
2:2
NIHR Journals Library
lam, Ching
58a25484-cacd-43c3-b191-623960c460b3
Tan, Wei
d91f9c26-d81e-49db-933f-3d379f16d732
Leighton, Matthew
644628da-fdc8-49d8-8da9-6858e2418e9c
Hastings, Margaret
b439b8f5-69a3-4172-ad6a-5acd5293f622
Lingaya, Melanie
f5e39ce0-fada-420b-9203-424d0f26feff
Falcone, Yirga
de054a46-9c89-4a00-b7fe-1a4e0f8e23f3
Zhou, Xiaoying
84558a96-3129-44de-b295-869d9ee4d19f
Xu, Luting
c298a7e6-405d-40f6-b6b7-fa8cbad0bd9c
Whorwell, Peter
23e4fc46-2028-4120-85a8-70dd31b9d618
Walls, Andrew F.
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Zaitoun, Abed
602cc881-defe-4bf3-a4eb-acf8f9555f78
Montgomery, Alan
6f6e4e9e-e78b-43b0-9334-05522cfd6cdf
Spiller, Robin
f4d64456-1f6a-4be4-9b3c-6d6532da24f9
lam, Ching
58a25484-cacd-43c3-b191-623960c460b3
Tan, Wei
d91f9c26-d81e-49db-933f-3d379f16d732
Leighton, Matthew
644628da-fdc8-49d8-8da9-6858e2418e9c
Hastings, Margaret
b439b8f5-69a3-4172-ad6a-5acd5293f622
Lingaya, Melanie
f5e39ce0-fada-420b-9203-424d0f26feff
Falcone, Yirga
de054a46-9c89-4a00-b7fe-1a4e0f8e23f3
Zhou, Xiaoying
84558a96-3129-44de-b295-869d9ee4d19f
Xu, Luting
c298a7e6-405d-40f6-b6b7-fa8cbad0bd9c
Whorwell, Peter
23e4fc46-2028-4120-85a8-70dd31b9d618
Walls, Andrew F.
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Zaitoun, Abed
602cc881-defe-4bf3-a4eb-acf8f9555f78
Montgomery, Alan
6f6e4e9e-e78b-43b0-9334-05522cfd6cdf
Spiller, Robin
f4d64456-1f6a-4be4-9b3c-6d6532da24f9

(2015) 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 (Efficacy and Mechanism Evaluation, , (doi:10.3310/eme02020), 2:2) Southampton, GB. NIHR Journals Library 84pp.

Record type: Monograph (Project Report)

Abstract

Background

Diarrhoea-predominant irritable bowel syndrome (IBS-D) is a common outcome after inflammation due to bacterial gastroenteritis. Several studies have shown ongoing immune activation in the mucosa of patients with IBS-D and a number of studies have suggested that mesalazine slow-release granule formulation (2?g; PENTASA®, Ferring Pharmaceuticals Ltd) may provide benefit including a reduction in stool frequency.

Objectives

Our primary aim was to compare the effect of mesalazine with placebo on stool frequency. Our secondary aims were to assess the effect of mesalazine on abdominal pain, stool consistency, urgency and satisfactory relief of irritable bowel syndrome (IBS) symptoms.

Design/participants/intervention

We performed a double-blind, randomised placebo-controlled trial of 2?g mesalazine twice daily compared with placebo for 3 months in Rome III criteria patients with IBS-D.

Settings

Participants were recruited from the primary care research network and secondary care hospitals. Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of ‘satisfactory relief of IBS symptoms’. Those recruited in Nottingham had sigmoid biopsies and/or magnetic resonance imaging of the abdomen at the start and end of the trial.

Results

A total of 136 patients with IBS-D (82 female, 54 male) were randomised; 10 patients withdrew from each group. Analysis by intention to treat showed that the mean daily average stool frequency during weeks 11 and 12 was 2.8 [standard deviation (SD) 1.2] in the mesalazine group and 2.7 (SD 1.9) in the placebo group, with a group difference of 0.1 (95% confidence interval –0.33 to 0.53); p?=?0.66.

Conclusions

Mesalazine did not improve abdominal pain, stool consistency or percentage with satisfactory relief compared with placebo during the last 2 weeks’ follow-up. A post hoc analysis in 13 postinfectious patients with IBS appeared to show benefit but this needs confirmation in a larger group. More precise subtyping based on underlying disease mechanisms may allow more effective targeting of treatment in IBS.

Trial registration

Current Controlled Trials ISRCTN76612274.

Funding

This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership.

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More information

Published date: 27 March 2015
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 375887
URI: http://eprints.soton.ac.uk/id/eprint/375887
ISSN: 2050-4365
PURE UUID: c65c2237-28aa-4b53-ad15-f26b3631ab75
ORCID for Andrew F. Walls: ORCID iD orcid.org/0000-0003-4803-4595

Catalogue record

Date deposited: 15 Apr 2015 13:40
Last modified: 18 Feb 2021 16:37

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Contributors

Author: Ching lam
Author: Wei Tan
Author: Matthew Leighton
Author: Margaret Hastings
Author: Melanie Lingaya
Author: Yirga Falcone
Author: Xiaoying Zhou
Author: Luting Xu
Author: Peter Whorwell
Author: Andrew F. Walls ORCID iD
Author: Abed Zaitoun
Author: Alan Montgomery
Author: Robin Spiller

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