Division of Gastroenterology and Hepatology, Digestive Health Center, Augusta University, Augusta, Georgia, USA.
Salix Pharmaceuticals, Bridgewater, New Jersey, USA.
Clin Transl Gastroenterol. 2023 Jul 1;14(7):e00598. doi: 10.14309/ctg.0000000000000598.
Chronic idiopathic constipation (CIC) is a common condition that affects some patient groups more often. Demographic/clinical characteristics can differ in presentation and therapeutic response. The impact of these characteristics on plecanatide efficacy/safety was examined.
Data from 2 identically designed, randomized, phase 3 trials of adults with CIC receiving 3 mg of plecanatide, 6 mg of plecanatide, or placebo for 12 weeks were analyzed. Subgroups were baseline age, body mass index (BMI), race/ethnicity, and sex/gender. Endpoints included durable overall complete spontaneous bowel movement (CSBM) responder rate, weekly CSBMs and spontaneous bowel movements (SBMs), and adverse events.
Overall (N = 2,639; 3 mg of plecanatide [n = 877]; 6 mg of plecanatide [n = 877]; and placebo [n = 885]), CSBM responder rates were significantly greater with 3 mg of plecanatide and 6 mg of plecanatide vs placebo in subgroups with those younger than 65 years ( P < 0.001), females ( P < 0.001), White individuals ( P < 0.001), and BMI <25 kg/m 2 ( P ≤ 0.004) and 25-30 kg/m 2 ( P < 0.001); as well, for 3 mg: 65 years or older ( P = 0.03), non-White individuals ( P < 0.001), and BMI ≥30 kg/m 2 ( P = 0.02). Improvement from baseline in weekly CSBM and SBM frequency occurred in all subgroups for both plecanatide doses vs placebo ( P ≤ 0.02) at week 12, except those aged 65 years or older for 6 mg of plecanatide. The most common adverse event was diarrhea (3 mg [4.9%]; 6 mg [5.4%]; and placebo [1.3%]).
Pooled data from identically designed CIC trials strengthened the ability to identify meaningful subgroup comparisons regarding plecanatide efficacy and safety.
慢性特发性便秘（CIC）是一种常见病症，某些患者群体的发病率更高。不同表现和治疗反应的患者在人口统计学/临床特征方面可能存在差异。本研究旨在评估这些特征对普卡那肽疗效/安全性的影响。
对两项设计相同的、评估普卡那肽治疗 CIC 成人患者的 3 期随机临床试验数据进行分析，患者分别接受 3mg、6mg 普卡那肽或安慰剂治疗 12 周。亚组人群包括基线年龄、体重指数（BMI）、种族/民族和性别/性别。终点包括持久整体完全自发性排便（CSBM）应答率、每周 CSBM 和自发性排便（SBM）以及不良事件。
总体（N=2639；3mg 普卡那肽[n=877]；6mg 普卡那肽[n=877]；安慰剂[n=885]）中，与安慰剂相比，3mg 和 6mg 普卡那肽在年龄＜65 岁（P＜0.001）、女性（P＜0.001）、白种人（P＜0.001）和 BMI＜25kg/m 2（P≤0.004）和 25-30kg/m 2（P＜0.001）亚组中的 CSBM 应答率显著更高；此外，3mg 普卡那肽在年龄≥65 岁（P=0.03）、非白种人（P＜0.001）和 BMI≥30kg/m 2（P=0.02）亚组中的 CSBM 应答率也更高。与安慰剂相比，两组普卡那肽在治疗 12 周时均能改善所有亚组的每周 CSBM 和 SBM 频率（P≤0.02），但 6mg 普卡那肽治疗 65 岁及以上患者除外。最常见的不良事件是腹泻（3mg：4.9%；6mg：5.4%；安慰剂：1.3%）。
来自两项设计相同的 CIC 试验的汇总数据增强了识别普卡那肽疗效和安全性方面有意义的亚组比较的能力。
