A meta-analysis of naldemedine for the treatment of opioid-induced constipation

ABSTRACT

Introduction: Opioid-induced constipation (OIC) is a common adverse effect in patients under long-term opioid therapy. Naldemedine is a novel peripherally acting μ-opioid receptor antagonists being developed for the treatment of OIC without affecting central analgesia. This meta-analysis is to assess the current evidence for efficacy and safety of naldemedine for the treatment of OIC.

Areas covered: We searched through MEDLINE, EMBASE, Web of Science and Cochrane Library, ‘ISRCTN Register’ and‘ClinicalTrials.gov’ (up to Aug 2018). Our final review included five randomized clinical trials (1751 participants in total), three trials observed naldemedine for the treatment of OIC in non-cancer patients and two trials in cancer patients. A Random Effects model was used for all comparisons. Subgroup analyses for the following subgroups were carried out: naldemedine 0.1 mg; 0.2 mg; 0.4 mg; cancer patients; non-cancer patients.

Expert opinion: Naldemedine improved the proportion of responders and spontaneous bowel movements frequency. The incidence of serious adverse effects (AEs) in naldemedine group was higher than placebo, especially in cancer patient subgroup. The AEs occurred in participants with naldemedine were mild to moderate and well tolerated during treatment. The results of this network meta-analysis will guide the future researchers in evaluating naldemedine for the treatment of OIC.

KEYWORDS:

• Meta-analysis
• naldemedine
• opioid-induced constipation
• chronic severe pain
• μ-receptor antagonist
• efficacy
• safety

Article highlights

• The OIC patients often have a poor quality of life and 40% to 60% of patients receiving opioids for chronic non-cancer pain would be affected by OIC.

• PAMORAs (Naloxone, alvimopan, naltrexone, naloxegol, and methylnaltrexone) are the leading way in the treatment of OIC.

• Naldemedine, a novel, orally active, PAMORAs, is efficacious in the treatment of OIC.

• The outcomes of this meta-analysis showed participants who were receiving naldemedine 0.1mg or 0.2mg or 0.4mg once per day for two weeks had statistically significantly higher SBM response rates than participants receiving placebo.

• Naldemedine 0.2 mg or 0.4 mg once per day also showed statistically significant improvements in weekly SBM frequency from baseline at week two than placebo.

• The efficacy was improved with the dose increased from 0.1 mg to 0.2 mg, but not improved when dose increased from 0.2 mg to 0.4 mg.

• Receiving naldemedine at the doses of 0.1 mg, 0.2 mg, and 0.4 mg once per day was generally well tolerated during the two weeks phase.

• The incidence of serious AEs with naldemedine treatment was higher in cancer patients subgroup.

• The outcomes of our meta-analysis demonstrated that naldemedine was just more effective than a placebo. There was no data that directly compared naldemedine with other types of PAMORAs or laxatives.

• We can look forward to more and direct evidence to be proven for efficacy and safety of naldemedine in further.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.