Efficacy of Naldemedine for the Treatment of Opioid-Induced Constipation: A Meta-Analysis
Mohammad Esmadi1, Dina Ahmad2, Alexander Hewlett3
1) Methodist Health System, 933 E Peirce St, Council Bluffs, Iowa 51503
2) Case Western Reserve University, 11100 Euclid Avenue, Cleveland, Ohio 44106
3) University of Nebraska Medical Center, 4400 Emile St., Omaha, NE 68105 USA
Background & Aim: Opioid induced constipation (OIC) is the most common side effect of opioid therapy. It can lead to a decreased quality of life. Naldemedine is a peripherally acting μ-opioid receptor antagonist that has been recently studied in randomized controlled trials (RCTs) for the management of OIC. The aim of this study is to perform a meta-analysis of existing clinical trials to estimate the efficacy and safety of naldemedine in opioid-induced constipation.
Methods: A systematic search of PubMed, CINAHL, Scopus, Cochrane database of systematic reviews, and ClinicalTrials.gov registry was performed in March 2018. Two independent reviewers systematically identified prospective RCTs published in the English language that compared the effect of oral naldemedine versus placebo in adults with OIC. Meta-analysis was performed using a random effects model to assess the primary outcome: spontaneous bowel movement (SBM) responder rates. Assessed secondary outcomes were: a change in SBM frequency per week from baseline during the treatment period, change from baseline in the frequency of complete SBM and incidence of treatment-emergent adverse events. Review Manager 5.3 software program was utilized for statistical analysis.
Results: Six RCTs met the inclusion criteria. A total of 2,762 patients were included in the meta-analysis. The proportion of SBM responders was significantly higher in the naldemedine group compared to the placebo group (56.4%, vs. 34.7%, p<0.00001). There was no statistically significant difference in treatment-emergent adverse events between naldemedine group and placebo group (mean odds ratio=1.18, p = 0.25, 95% CI: 0.89-1.55). Change in SBM frequency was higher in the naldemedine group versus placebo group (p<0.00001), as well as the change in complete SBM frequency.
Conclusions: Naldemedine 0.2 mg daily significantly improved symptoms in patients with opioid-induced constipation and was generally well tolerated. These results support the use of naldemedine for the treatment of opioid-induced constipation.
Key words: Naldemedine – opioid – constipation – opioid-induced constipation.
Abbreviation: AE: adverse event; BSS: Bristol Stool Scale; CNS: central nervous system; CSBM: complete spontaneous bowel movement; GI: gastrointestinal; OIC: opioid induced constipation; PAMORA: peripherally acting μ-opioid receptor antagonists; P-gp: P-glycoprotein; RCT: randomized controlled trial; SBM: spontaneous bowel movement.