Department of Respiratory Medicine, Iida Municipal Hospital, Iida, Nagano, Japan.
The First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
J Gastroenterol Hepatol. 2019 May;34(5):818-829. doi: 10.1111/jgh.14586. Epub 2019 Jan 16.
Opioid-induced constipation (OIC) is a frequent adverse event (AE) that impairs patients' quality of life (QOL). Peripherally acting μ-opioid receptor antagonists (PAMORAs) have been recognized as a treatment option for OIC, but the effect consistent across the studies has not been evaluated.
We conducted a quantitative meta-analysis to explore the efficacy of PAMORA for OIC (registered with PROSPERO: CRD42018085298). We systematically searched randomized controlled trials (RCTs) in Medline, Embase, and Central databases. Change from baseline in spontaneous bowel movements, pooled proportion of responders, QOL, and AEs were calculated and compared with results in placebo cases.
We included 31 RCTs with 7849 patients. A meta-analysis revealed that patients under PAMORA therapy had considerably improved spontaneous bowel movement from baseline compared with those given placebo (20 RCTs; mean difference, 1.43; 95% confidence interval [CI], 1.18-1.68; n = 5622) and more responded (21 RCTs; risk ratio [RR], 1.81; 95% CI, 1.55-2.12; n = 4821). Moreover, QOL of patients receiving PAMORA was significantly better (8 RCTs; mean difference, -0.22; 95% CI, -0.28 to -0.17; n = 2884). AEs were increased significantly in the PAMORA group (26 RCTs; RR, 1.10; 95% CI, 1.06-1.15; n = 7715), especially in gastrointestinal disorders, whereas serious AEs were not significant (17 RCTs; RR, 1.04; 95% CI, 0.85-1.28; n = 5890).
Peripherally acting μ-opioid receptor antagonist has been shown to be effective and durable for patients with OIC and is the only drug with confirmed evidence in meta-analysis. The possibility of publication bias was the limitation of this study.
阿片类药物诱导的便秘（OIC）是一种常见的不良反应（AE），会损害患者的生活质量（QOL）。外周作用μ-阿片受体拮抗剂（PAMORAs）已被认为是治疗 OIC 的一种选择，但尚未评估其在研究中的一致性效果。
我们进行了一项定量荟萃分析，以探讨 PAMORA 治疗 OIC 的疗效（在 PROSPERO 注册：CRD42018085298）。我们系统地检索了 Medline、Embase 和中央数据库中的随机对照试验（RCT）。从基线变化的自发性排便、应答者的汇总比例、QOL 和不良事件与安慰剂病例的结果进行了比较。
我们纳入了 31 项 RCT，共 7849 名患者。荟萃分析显示，与接受安慰剂的患者相比，接受 PAMORA 治疗的患者从基线开始的自发性排便有了显著改善（20 项 RCT；平均差异，1.43；95%置信区间[CI]，1.18-1.68；n=5622），且应答者更多（21 项 RCT；风险比[RR]，1.81；95% CI，1.55-2.12；n=4821）。此外，接受 PAMORA 的患者的 QOL 显著改善（8 项 RCT；平均差异，-0.22；95% CI，-0.28 至-0.17；n=2884）。PAMORA 组的不良事件显著增加（26 项 RCT；RR，1.10；95% CI，1.06-1.15；n=7715），尤其是胃肠道疾病，而严重不良事件则不显著（17 项 RCT；RR，1.04；95% CI，0.85-1.28；n=5890）。
外周作用μ-阿片受体拮抗剂已被证明对 OIC 患者有效且持久，是唯一在荟萃分析中具有确认证据的药物。本研究的局限性是存在发表偏倚的可能性。
