Department of Medicine, Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
Comprehensive Pain Center, Albany Medical College, Albany, NY, United States.
Pain. 2020 May;161(5):1027-1036. doi: 10.1097/j.pain.0000000000001754.
Constipation is the most common adverse event (AE) of opioid therapy. This multicenter, phase 2 study evaluated the efficacy and safety of linaclotide in treating opioid-induced constipation (OIC) in patients with chronic noncancer pain syndromes (NCT02270983). Adults with OIC (<3 spontaneous bowel movements [SBMs]/week) related to chronic noncancer pain were randomized 1:1:1 to receive linaclotide 145 µg, linaclotide 290 µg, or placebo once daily for 8 weeks. The primary endpoint was change from baseline in 8-week SBM frequency rate (SBMs/week). Secondary efficacy endpoints included 6/8-week SBM 3 + 1 responders, time to first SBM, and changes from baseline in 8-week stool consistency, abdominal bloating, and straining. Additional endpoints included treatment satisfaction and adequate relief responders. In total, 254 patients were randomized: 87, 88, and 79 received linaclotide 145 µg, linaclotide 290 µg, and placebo, respectively. The mean changes from baseline in SBMs/week during the treatment period were 2.9 and 3.5 in the linaclotide 145 and 290 µg groups (P < 0.01 for both doses), respectively, vs 1.6 in the placebo group. Diarrhea, the most common AE, was generally mild, resulting in 1.1%, 5.7%, and 1.3% of patients discontinuing in the linaclotide 145 μg, linaclotide 290 μg, and placebo groups, respectively. No serious AEs related to diarrhea were reported in any treatment group. Compared with placebo, linaclotide-treated patients had significant improvements in stool consistency, straining, abdominal bloating, and treatment satisfaction scores (P < 0.05). Linaclotide significantly improved OIC symptoms and was well tolerated in patients with chronic noncancer pain.
便秘是阿片类药物治疗中最常见的不良反应（AE）。这项多中心、2 期研究评估了利那洛肽治疗慢性非癌痛综合征患者阿片类药物诱导的便秘（OIC）的疗效和安全性（NCT02270983）。OIC（每周<3 次自发性排便[SBM]）与慢性非癌痛相关的成人患者按 1:1:1 的比例随机分为利那洛肽 145µg、利那洛肽 290µg 或安慰剂组，每日一次，共 8 周。主要终点为 8 周 SBM 频率（SBM/周）的基线变化。次要疗效终点包括 6/8 周 SBM3+1 应答者、首次 SBM 时间以及 8 周粪便稠度、腹胀和费力的基线变化。其他终点包括治疗满意度和充分缓解应答者。共 254 名患者随机分组：87、88 和 79 名患者分别接受利那洛肽 145µg、利那洛肽 290µg 和安慰剂治疗。治疗期间，SBM/周的平均变化分别为利那洛肽 145µg 和 290µg 组的 2.9 和 3.5（两种剂量均<0.01），安慰剂组为 1.6。腹泻是最常见的 AE，一般为轻度，分别导致利那洛肽 145µg、290µg 和安慰剂组的 1.1%、5.7%和 1.3%的患者停药。任何治疗组均未报告与腹泻相关的严重 AE。与安慰剂相比，利那洛肽治疗患者的粪便稠度、费力、腹胀和治疗满意度评分有显著改善（P<0.05）。利那洛肽显著改善了慢性非癌痛患者的 OIC 症状，且耐受性良好。
