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Efficacy of pharmacological therapies in patients with IBS with diarrhoea or mixed stool pattern: systematic review and network meta-analysis
  1. Christopher J Black1,2,
  2. Nicholas E Burr1,2,
  3. Michael Camilleri3,
  4. David L Earnest4,
  5. Eamonn MM Quigley5,
  6. Paul Moayyedi6,
  7. Lesley A Houghton1,
  8. Alexander C Ford1,2
  1. 1 Leeds Institute of Medical Research at St. James’s, University of Leeds, Leeds, UK
  2. 2 Leeds Gastroenterology Institute, St. James’s University Hospital, Leeds, UK
  3. 3 Mayo Clinic, Rochester, Minnesota, USA
  4. 4 Division of Gastroenterology, The University of Arizona College of Medicine, Tucson, Arizona, USA
  5. 5 Division of Gastroenterology and Hepatology, The Methodist Hospital, Weill Cornell Medical College, Houston, Texas, USA
  6. 6 Department of Gastroenterology, McMaster University, Hamilton, Ontario, Canada
  1. Correspondence to Professor Alexander C Ford, Leeds Gastroenterology Institute, St. James’s University Hospital, Leeds LS9 7TF, UK; alexf12399{at}


Objective Over half of patients with IBS have either diarrhoea (IBS-D) or a mixed stool pattern (IBS-M). The relative efficacy of licenced pharmacological therapies is unclear in the absence of head-to-head trials. We conducted a network meta-analysis to resolve this uncertainty.

Design We searched MEDLINE, Embase, Embase Classic, the Cochrane central register of controlled trials, and through January 2019 to identify randomised controlled trials (RCTs) assessing the efficacy of licenced pharmacological therapies (alosetron, eluxadoline, ramosetron and rifaximin) in adults with IBS-D or IBS-M. Trials included in the analysis reported a dichotomous assessment of overall response to therapy, and data were pooled using a random effects model. Efficacy and safety of all pharmacological therapies were reported as a pooled relative risk with 95% CIs to summarise the effect of each comparison tested. Treatments were ranked according to their p score.

Results We identified 18 eligible RCTs (seven alosetron, five ramosetron, two rifaximin and four eluxadoline), containing 9844 patients. All were superior to placebo for the treatment of IBS-D or IBS-M at 12 weeks, according to the Food and Drug Administration (FDA)-recommended endpoint for trials in IBS. Alosetron 1 mg twice daily was ranked first for efficacy, based on the FDA-recommended composite endpoint of improvement in both abdominal pain and stool consistency, effect on global symptoms of IBS and effect on stool consistency. Ramosetron 2.5µg once daily was ranked first for effect on abdominal pain. Total numbers of adverse events were significantly greater with alosetron 1 mg twice daily and ramosetron 2.5µg once daily, compared with placebo. Rifaximin 550 mg three times daily ranked first for safety. Constipation was significantly more common with all drugs, except rifaximin 550 mg three times daily.

Conclusion In a network meta-analysis of RCTs of pharmacological therapies for IBS-D and IBS-M, we found all drugs to be superior to placebo, but alosetron and ramosetron appeared to be the most effective.

  • stool consistency
  • effectiveness
  • treatment response
  • diarrhoea

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  • CJB and NEB are joint first authors.

  • Contributors Guarantor of the article: ACF is guarantor. Specific author contributions: all authors conceived and drafted the study. ACF and CJB collected all data. CJB, NEB and ACF analysed and interpreted the data. CJB, NEB and ACF drafted the manuscript. All authors commented on drafts of the paper. All authors have approved the final draft of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests MC has received research funding from Allergan. DLE has acted as a consultant for Prometheus Laboratories. EMMQ has acted as a consultant to Almirall, Synergy and Salix. PM has received honoraria from Allergan and Salix, and research funding from Allergan. LAH has acted as a consultant for, and received research funding from Takeda, USA, and has acted as a consultant for Pfizer, USA. ACF has acted as a consultant for and received researching funding from Almirall.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Correction notice This article has been corrected since it published Online First. The author statement has been added.

  • Patient consent for publication Not required.