Methodist Health System, 933 E Peirce St, Council Bluffs, Iowa 51503, USA.
Case Western Reserve University, 11100 Euclid Avenue, Cleveland, Ohio 44106, USA.
J Gastrointestin Liver Dis. 2019 Mar;28(1):41-46. doi: 10.15403/jgld.2014.1121.281.any.
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.
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.
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.
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.
阿片类药物诱导的便秘（OIC）是阿片类药物治疗中最常见的副作用。它会导致生活质量下降。Naldemedine 是一种外周作用的 μ 阿片受体拮抗剂，最近已在随机对照试验（RCT）中进行研究，用于治疗 OIC。本研究的目的是对现有临床试验进行荟萃分析，以评估naldemedine 治疗阿片类药物诱导的便秘的疗效和安全性。
2018 年 3 月，对 PubMed、CINAHL、Scopus、Cochrane 系统评价数据库和 ClinicalTrials.gov 注册中心进行了系统搜索。两名独立的审查员系统地确定了以英文发表的比较口服naldemedine 与安慰剂治疗 OIC 成人的效果的前瞻性 RCT。使用随机效应模型进行荟萃分析，以评估主要结局：自发性排便（SBM）应答率。评估的次要结局包括：治疗期间从基线开始每周 SBM 频率的变化、从基线开始 SBM 完全频率的变化和治疗中出现不良事件的发生率。使用 Review Manager 5.3 软件程序进行统计分析。
6 项 RCT 符合纳入标准。共有 2762 名患者纳入荟萃分析。与安慰剂组相比，naldemedine 组 SBM 应答者的比例明显更高（56.4% vs. 34.7%，p<0.00001）。naldemedine 组与安慰剂组之间的治疗中出现不良事件无统计学差异（平均比值比=1.18，p=0.25，95%CI：0.89-1.55）。与安慰剂组相比，naldemedine 组 SBM 频率的变化更高（p<0.00001），以及完全 SBM 频率的变化。
naldemedine 每日 0.2mg 可显著改善阿片类药物诱导的便秘患者的症状，且一般耐受性良好。这些结果支持使用 naldemedine 治疗阿片类药物诱导的便秘。
