Spierings Egilius L H, Rauck Richard, Brewer Randall, Marcuard Stefano, Vallejo Ricardo
Headache & Face Pain Program, Tufts Medical Center, and Craniofacial Pain Center, Tufts University School of Dental Medicine, Boston, Massachusetts, U.S.A.
The Carolinas Pain Institute, Winston-Salem, North Carolina, U.S.A.
Pain Pract. 2016 Nov;16(8):985-993. doi: 10.1111/papr.12347. Epub 2015 Aug 29.
Chronic opioid analgesic use often causes opioid-induced constipation (OIC). This open-label extension study evaluated the safety and efficacy of lubiprostone, a chloride channel (ClC-2) activator, for treatment of OIC in patients with chronic noncancer pain.
Adults with OIC were enrolled from two 12-week, placebo-controlled, double-blind studies and received lubiprostone 24 μg twice daily for up to 9 months. OIC was defined as < 3 spontaneous bowel movements (SBMs)/week during the 2-week baseline period, of which ≥ 25% were characterized by hard to very hard stool consistency, subjectively incomplete evacuation, and/or moderate or worse straining. Inclusion criteria required consistent treatment with full opioid agonists ≥ 30 days prior to screening and throughout the study.
All 439 patients who received lubiprostone were analyzed for safety and efficacy. Overall, 24.6% of patients reported treatment-related adverse events (AEs), most commonly nausea (5.0%), diarrhea (4.6%), headache (1.6%), and vomiting (1.4%). No treatment-related serious AEs were reported. Nausea and diarrhea each led to study discontinuation in 5 patients (1.1%); 2 cases each of nausea and diarrhea were rated as severe. Rescue medication usage decreased from month 1 (33.0%) to month 9 (18.6%). Mean weekly SBM frequency (1.4) was significantly increased from baseline at all months (P < 0.001, range 4.9 to 5.3). Straining, abdominal bloating, abdominal discomfort, stool consistency, constipation severity, and bowel habit regularity were significantly improved from baseline at all months (P < 0.001).
Lubiprostone treatment was well tolerated and improved symptoms and signs of OIC in this 9-month, open-label study of patients with chronic noncancer pain.
长期使用阿片类镇痛药常导致阿片类药物引起的便秘（OIC）。本开放标签扩展研究评估了氯通道（ClC-2）激活剂鲁比前列酮治疗慢性非癌性疼痛患者OIC的安全性和有效性。
患有OIC的成年人来自两项为期12周、安慰剂对照、双盲研究，接受鲁比前列酮24μg，每日两次，最长9个月。OIC定义为在2周基线期内每周自发排便次数（SBM）<3次，其中≥25%的特征为大便硬度为硬至非常硬、主观排便不净和/或中度或更严重的用力排便。纳入标准要求在筛查前至少30天及整个研究期间持续使用完全阿片类激动剂治疗。
对所有439例接受鲁比前列酮治疗的患者进行了安全性和有效性分析。总体而言，24.6%的患者报告了与治疗相关的不良事件（AE），最常见的是恶心（5.0%）、腹泻（4.6%）、头痛（1.6%）和呕吐（1.4%）。未报告与治疗相关的严重AE。恶心和腹泻各导致5例患者（1.1%）退出研究；恶心和腹泻各有2例被评为严重。急救药物的使用从第1个月（33.0%）降至第9个月（18.6%）。各月平均每周SBM频率（1.4次）均较基线显著增加（P<0.001，范围4.9至5.3）。各月用力排便、腹胀、腹部不适、大便硬度、便秘严重程度和排便习惯规律性均较基线显著改善（P<0.001）。
在这项针对慢性非癌性疼痛患者的为期9个月的开放标签研究中，鲁比前列酮治疗耐受性良好，改善了OIC的症状和体征。
