OBJECTIVES: Opioid treatment often leads to opioid-induced constipation (OIC). We compared the efficacy and safety of naldemedine 0.2mg (NLD), a peripherally-acting mu-opioid receptor antagonist, to alternative OIC treatments.

METHODS: A systematic literature review identified phase III/IV randomized controlled trials (RCTs) of EU-licensed OIC-indicated treatments in adults via searches of MEDLINE, Embase and the Cochrane Library from database inception to 14-Jun-2017, and of congresses, reference lists and grey literature. Outcomes at 12 and 52 weeks were assessed using indirect treatment comparisons (ITCs) or network meta-analyses (NMAs).

RESULTS: Of 26 identified placebo/usual care-controlled RCTs, six reported 12-week outcomes (three NLD; two naloxegol 12.5mg [NLX12.5]-vs-naloxegol 25mg [NLX25]; one oxycodone/naloxone). NMAs suggest that NLD was generally comparable to other treatments at 12 weeks for response rate, mean change from baseline in spontaneous bowel movements (SBMs), patient assessment of constipation-symptoms (PAC-SYM) questionnaire, all-cause discontinuation (ACD) and discontinuation due to adverse events (AEs), except that there was a lower risk of discontinuation due to AEs for oxycodone/naloxone over NLD (risk ratio [RR]: 0.22; 95% credible interval [95%CrI]: 0.07, 0.60), and NMAs of SBMs and PAC-SYM favored NLD over NLX12.5 (SBMs: difference -0.82; 95%CrI: -1.33, -0.32; PAC-SYM: difference 0.16; 95%CrI: 0.01, 0.30). ITCs of the two studies reporting 52-week outcomes showed NLD had a lower risk of total AEs (RR: 0.84; 95% confidence interval [95%CI]: 0.75, 0.94), discontinuation due to AEs (RR: 0.19; 95%CI: 0.07, 0.52) and flatulence (RR: 0.10; 95%CI: 0.03, 0.41) versus NLX25; no statistically significant differences were observed in abdominal pain, ACD, serious AEs, deaths, diarrhea, nausea, vomiting or major adverse cardiac events.

CONCLUSIONS: Efficacy of NLD and NLX25 was similar for OIC treatment, with an improved longer-term safety profile for NLD versus NLX25. 12-week comparisons suggest NLD is superior to NLX12.5 for the treatment of OIC in terms of SBMs and PAC-SYM.