Effective Constipation Treatment Changes More Than Bowel Frequency: A Systematic Review and Meta-Analysis

Bielefeldt, Klaus; Levinthal, David J.; Nusrat, Salman

doi:10.5056/jnm15171

Cited by 9 publications

(7 citation statements)

References 84 publications

(114 reference statements)

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“…Strengths in our study design and network meta-analysis include trials with similar patient population, comparators, outcome assessments and trial design; application of the GRADE approach to provide an objective and transparent assessment of the quality of evidence for evaluating comparative efficacy of these agents52 and the inclusion of the responder analyses as well as secondary end points, which are very relevant in view of differences in baseline SBM and CSBM between studies 53…”

Section: Discussionmentioning

confidence: 99%

Comparison of efficacy of pharmacological treatments for chronic idiopathic constipation: a systematic review and network meta-analysis

Nelson

Camilleri

Chirapongsathorn

et al. 2016

Gut

127

112

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Running title: Network meta-analysis of pharmacological agents for treatment of CIC Word count: 3745 (excluding abstract, summary box, acknowledgements, disclosures, references, table and figure legends) Key words: bisacodyl, elobixibat, linaclotide, lubiprostone, picosulfate, polyethylene glycol, prucalopride, tegaserod, velusetrag Abbreviations: chronic idiopathic constipation (CIC) numbers needed to treat (NNT) sodium picosulfate (NaP) polyethylene glycol (PEG) complete spontaneous bowel movements (CSBM) spontaneous bowel movements (SBM) weighted mean difference (WMD) confidence interval (CI) Study Selection: Phase IIB and phase III randomized, placebo-controlled trials (RCT) of ≥4weeks' treatment for CIC in adults with Rome II or III criteria for functional constipation; trials included at least 1 of 4 endpoints. Data Extraction and Synthesis:Two investigators independently evaluated all full text articles that met inclusion criteria and extracted data for primary and secondary endpoints, risk of bias and quality of evidence.Outcomes: Primary endpoints were ≥3 complete spontaneous bowel movements (CSBM)/week and increase over baseline by ≥1 CSBM/week. Secondary endpoints were change from baseline (∆ b ) in the number of SBM/week and ∆ b CSBM/week.Results: Twenty-one RCTs (9189 patients) met inclusion and endpoint criteria: 9 prucalopride, 3 lubiprostone, 3 linaclotide, 2 tegaserod, 1 each velusetrag, elobixibat, bisacodyl and sodium picosulphate (NaP). All pre-specified endpoints were unavailable in 4 polyethylene glycol studies. Bisacodyl, NaP, prucalopride and velusetrag were superior to placebo for the ≥3 CSBM/week endpoint. No drug was superior at improving the primary endpoints on network meta-analysis. Bisacodyl appeared superior to the other drugs for the secondary endpoint, ∆ b in number of SBM/week.

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Section: Discussionmentioning

confidence: 99%

Comparison of efficacy of pharmacological treatments for chronic idiopathic constipation: a systematic review and network meta-analysis

Nelson

Camilleri

Chirapongsathorn

et al. 2016

Gut

127

112

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“…There is a body of evidence supporting the notion that increasing bowel movement frequency is associated with reduction of abdominal pain. A systematic review 26 demonstrated that laxation attenuated pain in both chronic constipation and IBS-C , irrespective of the type of laxative. Metaregression analysis found more frequently weekly bowel motion significantly correlated with attenuations in pain scores in patients with chronic constipation and with IBS-C (P < 0.001) 26 **.…”

Section: Does Laxation Correlate With Reduction In Abdominal Pain?mentioning

confidence: 99%

Chronic constipation and abdominal pain: Independent or closely interrelated symptoms?

Wong

Hebbard

Gibson

et al. 2020

J of Gastro and Hepatol

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Constipation is both a symptom and a disorder, seen in both functional constipation and irritable bowel syndrome with constipation predominance (IBS-C). Despite the Rome IV criteria distinguishing between these conditions, they share many therapeutic approaches. This review aims to explore the relationship between constipation and abdominal pain, assess the evidence surrounding whether laxation improves abdominal pain, and whether such a response to laxation differs between IBS-C and functional constipation. In patients with functional constipation, increasing frequency of bowel motions by laxatives regardless of mechanism of action is associated with reductions in the severity of abdominal pain, supporting the role of constipation as a contributor to abdominal discomfort. In patients with IBS-C, evidence from systematic reviews indicates that abdominal pain is driven by factors additional to constipation alone and that visceral analgesic modulation is also needed to optimize pain. Changing definitions of IBS-C and heterogeneity in clinical trial design including end-points have raised uncertainty about the comparative ability of older laxatives without known neuromodulatory effects to improve chronic abdominal pain compared to new secretagogues and prokinetics for the management of IBS-C. While it is known that abdominal pain is associated with constipation and laxation contributes to relief of that pain, it remains unproven whether proposed visceral analgesic properties of new laxatives provide greater pain relief than laxation alone. However, it is likely that the response to laxation in IBS-C is only part of the puzzle.

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“…Pharmacological treatment options for patients with IBS‐C are limited, as only three agents, including lubiprostone, have received US Food and Drug Administration (FDA) approval, and one was subsequently withdrawn from US marketing . Lubiprostone, an activator of the ClC‐2 chloride channel on the apical surface of enterocytes in the small intestine, was approved in 2008 for the treatment of IBS‐C (8 μg b.d.)…”

Section: Introductionmentioning

confidence: 99%

Effects of baseline abdominal pain and bloating on response to lubiprostone in patients with irritable bowel syndrome with constipation

Chang

Chey

Drossman

et al. 2016

Aliment Pharmacol Ther

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SummaryBackgroundLubiprostone (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.AimIn a post hoc analysis, similar criteria were applied to data from two pivotal, phase 3, double‐blind, randomised trials of lubiprostone in patients with IBS‐C.MethodsIncluded patients had a baseline spontaneous bowel movement (SBM) frequency <3/week and abdominal pain or bloating ratings ≥1.36 on a 5‐point scale [0 (absent) to 4 (very severe)]. Responders (composite endpoint) had a mean pain reduction ≥30% compared with baseline, and an increase from baseline of ≥1 SBM/week for ≥6 of the 12 treatment weeks. Lubiprostone effects on abdominal pain alone were also evaluated, as were bloating alone and in a composite endpoint with stool frequency.ResultsIn pooled data, 325 patients received lubiprostone and 180 received placebo. Rates of response were higher with lubiprostone vs. placebo for the composite endpoint of improved pain and stool frequency (26.3% vs. 15.3%, respectively; P = 0.008) and the composite endpoint of improved bloating and stool frequency (23.8% vs. 12.6%, respectively; P = 0.012). Response rates were also higher with lubiprostone vs. placebo for abdominal pain alone (P = 0.005) and bloating alone (P = 0.012).ConclusionLubiprostone was significantly more effective than placebo in improving abdominal pain or bloating, and also in composite endpoints that included stool frequency.

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Effective Constipation Treatment Changes More Than Bowel Frequency: A Systematic Review and Meta-Analysis

Cited by 9 publications

References 84 publications

Comparison of efficacy of pharmacological treatments for chronic idiopathic constipation: a systematic review and network meta-analysis

Comparison of efficacy of pharmacological treatments for chronic idiopathic constipation: a systematic review and network meta-analysis

Chronic constipation and abdominal pain: Independent or closely interrelated symptoms?

Effects of baseline abdominal pain and bloating on response to lubiprostone in patients with irritable bowel syndrome with constipation

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