Dataset Information

Efficacy and Tolerability of Guanylate Cyclase-C Agonists for Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation: A Systematic Review and Meta-Analysis.

ABSTRACT: OBJECTIVES:Linaclotide and plecanatide are guanylate cyclase-C (GCC) agonists for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). Our objective is to evaluate the efficacy and tolerability of GCC agonists based on data from multiple randomized controlled trials (RCTs). METHODS:We searched PubMED, EMBASE, Cochrane databases, clinicaltrials.gov, major conference abstracts, Food and Drug Administration (FDA) websites, and United States Securities and Exchange Commission filings of drug sponsors to identify RCTs of CIC or IBS-C patients. We assessed efficacy based on FDA-approved composite responder endpoints, diarrhea as an adverse event, and study withdrawal owing to diarrhea for each therapy. Trial results were pooled using DerSimonian and Laird random effects model of meta-analysis and exact logistic regression when appropriate with 95% confidence intervals. Meta-regression was performed to compare outcomes between therapies adjusting for placebo event rate. RESULTS:Eight linaclotide trials (five CIC; three IBS-C) and seven plecanatide trials (four CIC; three IBS-C) evaluating 10,369 patients met inclusion criteria. FDA publications documented that different definitions for diarrhea were used in linaclotide vs. plecanatide trials. Both drugs were efficacious in treating CIC (linaclotide 72??g (Odds ratio (OR)=3.11, 95% CI 1.81-5.34); linaclotide 145??g (OR=3.25, 2.15-4.91); plecanatide 3?mg (OR=1.99, 1.57-2.51)) and IBS-C (linaclotide 290??g (OR=2.43, 1.48-3.98); plecanatide 3?mg (OR=1.87, 1.47-2.38); plecanatide 6?mg (OR=1.92, 1.48-2.48)). Diarrhea occurred in excess of placebo in treating CIC (linaclotide 72??g (OR=3.07, 1.97-4.77); linaclotide 145??g (OR=3.70, 2.69-5.10); plecanatide 3?mg (OR=3.86, 1.83-8.12)) and IBS-C (linaclotide 290??g (OR=8.02, 5.20-12.37); plecanatide 3?mg (OR=5.55, 1.62-19.00); plecanatide 6?mg (OR=4.13, 1.57-10.83)). Based on meta-regression, there were no statistically significant differences between therapies in odds ratios for efficacy, diarrhea, or diarrhea-related study withdrawals. CONCLUSIONS:Both linaclotide and plecanatide demonstrate similar efficacy and tolerability in treating IBS-C and CIC. No differences in odds of diarrhea were seen between linaclotide and plecanatide.

SUBMITTER: Shah ED

PROVIDER: S-EPMC7213047 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Efficacy and Tolerability of Guanylate Cyclase-C Agonists for Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation: A Systematic Review and Meta-Analysis.

Shah Eric D ED Kim Hyungjin Myra HM Schoenfeld Philip P

The American journal of gastroenterology 20180130 3

<h4>Objectives</h4>Linaclotide and plecanatide are guanylate cyclase-C (GCC) agonists for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). Our objective is to evaluate the efficacy and tolerability of GCC agonists based on data from multiple randomized controlled trials (RCTs).<h4>Methods</h4>We searched PubMED, EMBASE, Cochrane databases, clinicaltrials.gov, major conference abstracts, Food and Drug Administration (FDA) websites, and ...[more]

PMID: 29380823

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Project description:IntroductionTo inform the patient-centered discussion regarding comparative outcomes with irritable bowel syndrome/chronic idiopathic constipation pharmacotherapy, we evaluated reasons and timing of discontinuation of FDA-approved pharmacotherapy for irritable bowel syndrome and chronic idiopathic constipation in a large observational real-world cohort.MethodsWe identified patients initiating lubiprostone or linaclotide within the University of Michigan Electronic Medical Record (2012-2016). Medication start and stop dates were determined in manual chart review including detailed review of all documentation including office notes and telephone encounters. A Cox model was constructed to predict the hazard of discontinuation.ResultsOn multivariate analysis of 1,612 patients, linaclotide users had a lower risk of discontinuing therapy than lubiprostone users for any reason (hazard ratio [HR] = 0.6, 95% confidence interval [CI] 0.5-0.8). At 3 and 12 months, the overall discontinuation rates were 23% and 43% for lubiprostone compared with 14% and 24% for linaclotide. Over the first year of therapy, more than half of discontinuations due to intolerance occurred in the first 3 months for both drugs. Linaclotide users were more likely to discontinue due to intolerance (HR = 1.6 [95% CI, 1.2-2.3]) but less likely to discontinue due to insufficient efficacy of therapy (HR = 0.5 [95% CI, 0.4-0.8]). IBS diagnosis increased the hazard of discontinuation of lubiprostone relative to linactolide (HR = 1.4, 95% CI, 1.1-1.6). Loss of prescription drug coverage remained a common reason for discontinuation over the first year of therapy.DiscussionIndividuals appear more likely to discontinue lubiprostone than linaclotide overall, but more likely to discontinue linaclotide compared with lubiprostone due to intolerance (mostly diarrhea). Most discontinuations due to intolerance occur in the first 3 months. These results may be useful in individualized treatment selection and enhancing patient knowledge regarding long-term outcomes.

Project description:In this study, we aim to evaluate the efficacy and safety of acupoint catgut embedding for the treatment of diarrhea-predominant irritable bowel syndrome and constipation-predominant irritable bowel syndrome. We searched seven online databases to collect studies published up to Feb 29th, 2020. Study quality of each included article was evaluated by the Cochrane Collaboration Risk of Bias Tool. Systematic reviews and meta-analyses were conducted based on the Cochrane systematic review method by using RevMan 5.3 software. Among the included trials, acupoint catgut embedding alone or plus oral western medicine or plus other acupoint-based therapies, or plus oral traditional Chinese medicine were the main therapies in the experimental groups. Interventions in control groups mainly include oral western medicine alone, other acupoint-based therapies alone, or other acupoint-based therapies alone. Primary outcomes in this study include recovery rate, accumulative marked effective rate, accumulative effective rate, and recurrence rate. Finally, 30 trials involving 1889 participants were included. The results of systematic reviews and meta-analyses show that acupoint catgut embedding alone or plus oral western medicine or plus other acupoint-based therapy or plus oral traditional Chinese medicine was significantly better compared with using oral western medicine alone in terms of efficacy for IBS-C and IBS-D. In addition, acupoint catgut embedding alone or plus oral western medicine or plus other acupoint-based therapy or plus oral traditional Chinese medicine could improve the effective rate and decrease the recurrence rate for IBS-D compared with using oral western medicine, other acupoint-based therapies, or oral traditional Chinese medicine alone. Adverse events of acupoint catgut embedding include local induration, redness, swelling, and itchiness, but they were all mild and disappeared swiftly with ordinary local interventions. There is an urgent need for RCTs of high quality and large sample size and with longer treatment duration and follow-up periods of acupoint catgut embedding for IBS.

Dataset Information

Efficacy and Tolerability of Guanylate Cyclase-C Agonists for Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation: A Systematic Review and Meta-Analysis.

Publications

Efficacy and Tolerability of Guanylate Cyclase-C Agonists for Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation: A Systematic Review and Meta-Analysis.

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