Abstract
Background In the 2010s, medications with new mechanisms were introduced in Japan for the treatment of chronic idiopathic constipation (CIC). A few systematic reviews have compared medications' relative efficacy, but the reviews included studies on patients from various races, even though the mechanism of CIC is considered to differ between races. The aim of this study was to use a systematic review and network meta-analysis to compare the relative efficacy of these medications in Japanese patients. Methods We conducted a meta-analysis and report it here according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We identified studies by searching MEDLINE (via the PubMed interface) and the Cochrane Library and ICHUSHI databases and included randomized clinical trials that compared medications for CIC with placebo in Japanese adults. Two reviewers independently screened and assessed articles, abstracted data, and assessed the risk of bias. We pooled data by random-effects meta-analyses and also performed a Bayesian network meta-analysis to indirectly compare data. Results The present systematic review and meta-analyses included 1460 patients in 6 randomized clinical trials: 2 on linaclotide, 3 on elobixibat, 2 on lubiprostone, and 1 on lactulose. The results of direct comparisons showed that linaclotide, elobixibat, and lubiprostone were superior to placebo in the change of spontaneous bowel movements (SBMs) within 1 week: linaclotide, 1.95 (95% CI, 1.51-2.39); elobixibat, 5.69 (95% CI, 3.31-8.07); and lubiprostone, 2.41 (95% CI, 0.82-4.01). The Bayesian network meta-analysis showed consistent results. Elobixibat 10 mg was ranked first for the increase in SBMs and complete SBMs within 1 week and the time to first SBM. Lubiprostone 48 μg was ranked first for the proportion of patients with SBM within 24 hours. Conclusion Our direct and indirect meta-analyses revealed that the new CIC medications available in Japan have equal efficacy but that elobixibat and lubiprostone are highly likely to be more efficacious.
Highlights
Chronic idiopathic constipation (CIC) is highly prevalent in Japan [1, 2]
The protocol for this systematic review and network meta-analysis was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42020167825) [18], and the study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [19]
Eligible studies had to meet the following criteria: (1) the study was a published Randomized clinical trials (RCTs) with at least 1week follow-up; (2) the study population comprised Japanese adults with chronic idiopathic constipation (CIC) diagnosed according to the Rome II, III, or IV criteria or variations of these; (3) the studied CIC medications were available in Japan at the time of the literature search for the present analysis, and the study compared their dosage forms with each other or with placebo; (4) the study evaluated relevant outcome measurements of bowel function, including spontaneous bowel movements (SBMs); (5) the publication was written in English or Japanese; and (6) the study was published from 1 January 2010 to 31 December 2019 and included medications that were approved in the 2010s in Japan
Summary
Chronic idiopathic constipation (CIC) is highly prevalent in Japan [1, 2]. It impairs quality of life and causes a significant social and economic burden, and full recovery is difficult to achieve. A few systematic reviews have compared medications’ relative efficacy, but the reviews included studies on patients from various races, even though the mechanism of CIC is considered to differ between races. The aim of this study was to use a systematic review and network meta-analysis to compare the relative efficacy of these medications in Japanese patients. The present systematic review and meta-analyses included 1460 patients in 6 randomized clinical trials: 2 on linaclotide, 3 on elobixibat, 2 on lubiprostone, and 1 on lactulose. Our direct and indirect meta-analyses revealed that the new CIC medications available in Japan have equal efficacy but that elobixibat and lubiprostone are highly likely to be more efficacious
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