TY - JOUR
T1 - Efficacy of pharmacological therapies in patients with IBS with diarrhoea or mixed stool pattern
T2 - systematic review and network meta-analysis
AU - Black, Christopher J.
AU - Burr, Nicholas E.
AU - Camilleri, Michael
AU - Earnest, David L.
AU - Quigley, Eamonn M.M.
AU - Moayyedi, Paul
AU - Houghton, Lesley A.
AU - Ford, Alexander C.
N1 - Funding Information:
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.
Publisher Copyright:
© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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 Clinicaltrials.gov 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.
AB - 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 Clinicaltrials.gov 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.
KW - diarrhoea
KW - effectiveness
KW - stool consistency
KW - treatment response
KW - Abdominal Pain/drug therapy
KW - Humans
KW - Randomized Controlled Trials as Topic/methods
KW - Irritable Bowel Syndrome/complications
KW - Treatment Outcome
KW - Pain Management/standards
KW - Diarrhea/drug therapy
KW - Treatment Failure
KW - Endpoint Determination/standards
KW - Gastrointestinal Agents/adverse effects
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U2 - 10.1136/gutjnl-2018-318160
DO - 10.1136/gutjnl-2018-318160
M3 - Article
C2 - 30996042
AN - SCOPUS:85064522070
SN - 0017-5749
VL - 69
SP - 74
EP - 82
JO - Gut
JF - Gut
IS - 1
ER -