Efficacy of Secretagogues in Patients With Irritable Bowel Syndrome With Constipation: Systematic Review and Network Meta-analysis.

Published on Dec 1, 2018in Gastroenterology17.373
· DOI :10.1053/J.GASTRO.2018.08.021
Christopher J Black13
Estimated H-index: 13
(University of Leeds),
Nicholas E Burr14
Estimated H-index: 14
(University of Leeds)
+ 3 AuthorsAlexander C. Ford86
Estimated H-index: 86
(University of Leeds)
Sources
Abstract
Background & Aims Several secretagogues have been approved for the treatment of irritable bowel syndrome with constipation (IBS-C). However, their relative efficacy is unclear because there have been no head-to-head randomized controlled trials. We conducted a network meta-analysis to compare their efficacies in patients with IBS-C. Methods We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane Central Register of Controlled Trials through June 2018 to identify randomized controlled trials assessing the efficacy of secretagogues in adults with IBS-C. 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 secretagogues were reported as a pooled relative risk with 95% confidence interval to summarize the effect of each comparison tested, and treatments were ranked according to their P score. Results We identified 15 eligible randomized controlled trials of secretagogues that included 8462 patients. Linaclotide, lubiprostone, plecanatide, and tenapanor were superior to placebo for the treatment of IBS-C. Linaclotide (290 μg once daily) was ranked first in efficacy based on the end point recommended by the Food and Drug Administration for trials in IBS-C, the primary end point used in each trial, abdominal pain, and complete spontaneous bowel movements. Tenapanor (50 mg twice daily) was ranked first for decreasing bloating. Total numbers of adverse events were significantly larger with linaclotide (290 and 500 μg once daily) and plecanatide (3 mg once daily) compared with placebo. However, plecanatide 6 mg once daily ranked first for safety. Diarrhea was significantly more common with all drugs, except lubiprostone (8 μg twice daily). Nausea was significantly more common in patients who received lubiprostone. Conclusions In a network analysis of randomized controlled trials of secretagogues for IBS-C, we found all drugs to be superior to placebo. Efficacy was similar among individual drugs and dosages for most end points. However, data were extracted at the 12-week time point, so the long-term relative efficacy of these drugs is unknown.
Download
📖 Papers frequently viewed together
1,135 Citations
52 Citations
201919.82Gut
References32
Newest
#1Yunsheng Yang (Chinese PLA General Hospital)H-Index: 7
#2Jing-Yuan Fang (Renji Hospital)H-Index: 61
Last. Sam Lim (AstraZeneca)H-Index: 2
view all 16 authors...
BACKGROUND AND AIM: Linaclotide is a guanylate cyclase-C agonist approved in multiple countries to treat irritable bowel syndrome with constipation (IBS-C). China has unmet need for well-tolerated therapy that is effective in treating both bowel and abdominal symptoms of IBS-C. This trial evaluated linaclotide's efficacy and safety in IBS-C patients in China and other regions. METHODS: This Phase 3, double-blind trial randomized IBS-C patients to once-daily oral 290-μg linaclotide or placebo at ...
16 CitationsSource
#1Shin Fukudo (Tohoku University)H-Index: 54
#2A. Nakajima (YCU: Yokohama City University)H-Index: 11
Last. Hiroto Miwa (Hyogo College of Medicine)H-Index: 54
view all 9 authors...
BACKGROUND:Clinical testing to determine a suitable dose of linaclotide for Japanese patients with irritable bowel syndrome with constipation (IBS-C) was needed. METHODS:This was a randomized, double-blind, placebo-controlled, dose-finding trial. Japanese patients with IBS-C diagnosed using Rome III criteria (n = 559, men/women: 49/510) were randomly assigned to 1 of 4 linaclotide doses (0.0625, 0.125, 0.25, or 0.5 mg) or placebo for the 12-week treatment period. The primary endpoint was respond...
14 CitationsSource
#1Darren M. Brenner (NU: Northwestern University)H-Index: 17
#2Ronald FogelH-Index: 14
Last. Patrick GriffinH-Index: 6
view all 10 authors...
Two identical, phase 3, randomized, double-blind, placebo-controlled trials evaluated the efficacy and safety of plecanatide in patients with irritable bowel syndrome with constipation (IBS-C). Adults meeting Rome III criteria for IBS-C were randomized (1:1:1) to placebo or plecanatide (3 or 6 mg) for 12 weeks. The primary efficacy end point was the percentage of overall responders (patients reporting ≥30% reduction from baseline in worst abdominal pain plus an increase of ≥1 complete spontaneou...
54 CitationsSource
#1Eric D Shah (UM: University of Michigan)H-Index: 3
#2Hyungjin Myra Kim (UM: University of Michigan)H-Index: 60
Last. Philip Schoenfeld (UM: University of Michigan)H-Index: 32
view all 3 authors...
Efficacy and Tolerability of Guanylate Cyclase-C Agonists for Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation: A Systematic Review and Meta-Analysis
48 CitationsSource
#1William D. Chey (UM: University of Michigan)H-Index: 78
#2Anthony Lembo (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 71
Last. David P RosenbaumH-Index: 2
view all 3 authors...
Tenapanor Treatment of Patients With Constipation-Predominant Irritable Bowel Syndrome: A Phase 2, Randomized, Placebo-Controlled Efficacy and Safety Trial
52 CitationsSource
#1Lin Chang (UCLA: University of California, Los Angeles)H-Index: 73
#1Lin Chang (UCLA: University of California, Los Angeles)H-Index: 2
Last. S. MareyaH-Index: 1
view all 7 authors...
SummaryBackground Lubiprostone (8 μg b.d.) received US Food and Drug Administration (FDA) approval in 2008 for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) in women aged ≥18 years. In 2012, the FDA issued new guidance for IBS-C clinical trials, recommending a composite endpoint incorporating both abdominal pain and stool frequency. Aims In a post hoc analysis, similar criteria were applied to data from two pivotal, phase 3, double-blind, randomised trials of lubipro...
20 CitationsSource
#1Mark FisherH-Index: 1
#2Andrew Walker (Glas.: University of Glasgow)H-Index: 30
Last. Leandro LindnerH-Index: 1
view all 7 authors...
Presently, linaclotide is the only EMA-approved therapy indicated for the treatment of irritable bowel syndrome with constipation (IBS-C). This study sought to determine the cost-effectiveness of linaclotide compared to antidepressants for the treatment of adults with moderate to severe IBS-C who have previously received antispasmodics and/or laxatives. A Markov model was created to estimate costs and QALYs over a 5-year time horizon from the perspective of NHS Scotland. Health states were based...
5 CitationsSource
#1Gerta Rücker (University of Freiburg)H-Index: 48
#2Guido Schwarzer (University of Freiburg)H-Index: 55
Background Network meta-analysis is used to compare three or more treatments for the same condition. Within a Bayesian framework, for each treatment the probability of being best, or, more general, the probability that it has a certain rank can be derived from the posterior distributions of all treatments. The treatments can then be ranked by the surface under the cumulative ranking curve (SUCRA). For comparing treatments in a network meta-analysis, we propose a frequentist analogue to SUCRA whi...
389 CitationsSource
#1Brian Hutton (U of O: University of Ottawa)H-Index: 66
#2Georgia Salanti (UoI: University of Ioannina)H-Index: 76
Last. David Moher (U of O: University of Ottawa)H-Index: 129
view all 17 authors...
The PRISMA statement is a reporting guideline designed to improve the completeness of reporting of systematic reviews and meta-analyses. Authors have used this guideline worldwide to prepare their reviews for publication. In the past, these reports typically compared 2 treatment alternatives. With the evolution of systematic reviews that compare multiple treatments, some of them only indirectly, authors face novel challenges for conducting and reporting their reviews. This extension of the PRISM...
2,128 CitationsSource
#1Paul Moayyedi (McMaster University)H-Index: 115
#2Eamonn Martin QuigleyH-Index: 120
Last. Alexander C. Ford (St James's University Hospital)H-Index: 86
view all 9 authors...
The Effect of Fiber Supplementation on Irritable Bowel Syndrome: A Systematic Review and Meta-analysis
198 CitationsSource
Cited By68
Newest
#1Christopher J Black (University of Leeds)H-Index: 13
#2Heidi M Staudacher (Deakin University)H-Index: 20
Last. Alexander C. Ford (University of Leeds)H-Index: 86
view all 3 authors...
Objective null A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) is recommended for irritable bowel syndrome (IBS), if general lifestyle and dietary advice fails. However, although the impact of a low FODMAP diet on individual IBS symptoms has been examined in some randomised controlled trials (RCTs), there has been no recent systematic assessment, and individual trials have studied numerous alternative or control interventions, meaning the best com...
Source
#1Brigida Barberio (UNIPD: University of Padua)H-Index: 7
#2Ciaran Judge (St James's University Hospital)H-Index: 1
Last. Alexander C. Ford (University of Leeds)H-Index: 86
view all 4 authors...
Summary null Background null Functional constipation is a common functional bowel disorder in the community, which has a varying prevalence across cross-sectional surveys. We did a contemporaneous systematic review and meta-analysis of studies using comparable methodology and all iterations of the Rome criteria to estimate the global prevalence of functional constipation. null Methods null In this systematic review and meta-analysis, we searched MEDLINE, Embase, and Embase Classic from Jan 1, 19...
1 CitationsSource
#1Laurie Keefer (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 40
#2Cynthia W. Ko (UW: University of Washington)H-Index: 25
Last. Alexander C. Ford (University of Leeds)H-Index: 86
view all 3 authors...
Description null This expert review summarizes approaches to management of pain in disorders of gut–brain interaction. This review focuses specifically on approaches to pain that persist if first-line therapies aimed at addressing visceral causes of pain are unsuccessful. The roles of a therapeutic patient–provider relationship, nonpharmacologic and pharmacologic therapies, and avoidance of opioids are discussed. null null null Methods null This was not a formal systematic review but was based o...
Source
Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction which can have a considerable impact on quality of life. Following diagnosis, timely and evidence-based management is vital to the care of patients with IBS, aiming to improve outcomes, and enhance patient satisfaction. Good communication is paramount, and clinicians should provide a clear explanation about the disorder, with a focus on exploring the patient’s own beliefs about IBS, and a discussion of any concerns they...
Source
#1Alfred D. Nelson (Mayo Clinic)H-Index: 10
#2Christopher J Black (St James's University Hospital)H-Index: 13
Last. Alexander C. Ford (University of Leeds)H-Index: 86
view all 6 authors...
Source
Source
#1Alfred D. Nelson (Mayo Clinic)H-Index: 10
#2Christopher J Black (St James's University Hospital)H-Index: 13
Last. Alexander C. Ford (University of Leeds)H-Index: 86
view all 6 authors...
BACKGROUND Although bloating is a highly prevalent and troublesome symptom in irritable bowel syndrome with constipation (IBS-C), treatment is empirical with no specific guidelines for its management. AIM To conduct a pairwise and network meta-analysis, using a frequentist approach, of Food and Drug Administration-licensed drugs for IBS-C comparing their efficacy for abdominal bloating as a specific endpoint. METHODS We searched the medical literature through December 2020 to identify randomised...
2 CitationsSource
#1Robyn RexwinkelH-Index: 3
Last. Merit M. Tabbers (UvA: University of Amsterdam)H-Index: 29
view all 5 authors...
CONTEXT: Functional abdominal pain disorders (FAPDs) are common in childhood, impacting quality of life and school attendance. There are several compounds available for the treatment of pediatric FAPDs, but their efficacy and safety are unclear because of a lack of head-to-head randomized controlled trials (RCTs). OBJECTIVE: To systematically review the efficacy and safety of the pharmacologic treatments available for pediatric FAPDs. DATA SOURCES: Electronic databases were searched from incepti...
1 CitationsSource
#1Vivek C. Goodoory (University of Leeds)
#2Lesley A. Houghton (University of Leeds)H-Index: 53
Last. Alexander C. Ford (University of Leeds)H-Index: 86
view all 5 authors...
ABSTRACT Objectives Irritable bowel syndrome (IBS) is a chronic functional bowel disorder diagnosed using the Rome criteria, which have evolved since their original description 30 years ago. Little is known about the effects on the natural history of IBS of moving to the latest iteration, Rome IV, from the previous Rome III criteria. We conducted a 12-month longitudinal follow-up study examining this. Methods We collected complete demographic, symptom, mood, and psychological health data at base...
1 CitationsSource
#1Christopher J Black (University of Leeds)H-Index: 13
#2Alexander C. Ford (University of Leeds)H-Index: 86
Source