Original ResearchFull Report: Clinical—Alimentary TractEfficacy of Secretagogues in Patients With Irritable Bowel Syndrome With Constipation: Systematic Review and Network Meta-analysis
Section snippets
Search Strategy and Study Selection
A search of the medical literature was conducted using MEDLINE (1947 to June 2018), EMBASE, EMBASE Classic (1947 to June 2018), and the Cochrane Central Register of Controlled Trials. We also searched clinicaltrials.gov for unpublished trials or supplementary data for potentially eligible studies. RCTs examining the effect of secretagogues (lubiprostone, linaclotide, plecanatide, and tenapanor) in adult patients (>16 years) with IBS-C were eligible for inclusion (Supplementary Table 1).
Results
The search strategy generated 1163 citations, 75 of which appeared to be relevant to the systematic review and were retrieved for further assessment (Figure 1). Of these, 62 were excluded for various reasons, leaving 13 eligible articles reporting on 15 trials that included a total of 8462 patients. There were 3 RCTs reported in 2 articles20, 21 of lubiprostone in IBS-C, 6 trials of linaclotide (4 of which used linaclotide 290 μg once daily [od], the licensed dose in the United States,22, 23, 24
Discussion
This systematic review and network meta-analysis demonstrated that all secretagogues tested in IBS-C to date were more effective than placebo for global symptoms. Although all drugs performed similarly, linaclotide 290 μg od was ranked first for efficacy for global symptoms. This was irrespective of the outcome measure used, whether the FDA-recommended end point to define relief of global symptoms in IBS-C or the primary end point used to define global symptom improvement in each trial. For the
Acknowledgments
We are grateful to Dr Takeshi Kanno for translation of one of the eligible articles.
Author contributions: Christopher J. Black, Nicholas E. Burr, Eamonn M.M. Quigley, Paul Moayyedi, Lesley A. Houghton, and Alexander C. Ford conceived and drafted the study. Alexander C. Ford and Christopher J. Black collected all data. Christopher J. Black, Alexander C. Ford, and Nicholas E. Burr analyzed and interpreted the data. Christopher J. Black, Alexander C. Ford, and Nicholas E. Burr drafted the
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Conflicts of interest Christopher J. Black and Nicholas E. Burr report no conflicts of interest. Eamonn M.M. Quigley has acted as a consultant for Allergan, Ironwood, Salix, Synergy, and Vibrant and received research funding from Vibrant and 4D Pharma. Paul Moayyedi has acted as a consultant for Allergan, Lupin, Shire, and Takeda and received research funding from Allergan and Takeda. Lesley A. Houghton has acted as a consultant for Pfizer USA and received research funding from Takeda USA. Alexander C. Ford has acted as a consultant for and received researching funding from Almirall.
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Authors share co-senior authorship.