按年龄、体重指数和肾功能分层的慢性特发性便秘患者中普芦卡必利的疗效和安全性：III期和IV期随机、安慰剂对照临床研究的事后分析

Efficacy and safety of prucalopride in patients with chronic idiopathic constipation stratified by age, body mass index, and renal function: a post hoc analysis of phase III and IV, randomized, placebo-controlled clinical studies.

作者信息

Lembo Anthony, Staller Kyle, Boules Mena, Feuerstadt Paul, Spalding William, Gabriel André, Youssef Ashraf, Xie Yunlong, Terreri Brian, Cash Brooks D

机构信息

Digestive Disease Institute, Cleveland Clinic, Main Campus, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.

出版信息

Therap Adv Gastroenterol. 2024 Dec 10;17:17562848241299731. doi: 10.1177/17562848241299731. eCollection 2024.

BACKGROUND

Prucalopride (1 or 2 mg once daily) is approved for treating adults with chronic idiopathic constipation (CIC).

OBJECTIVES

We determined the effect of age, body mass index (BMI), and renal function on the efficacy and safety of prucalopride in adults with CIC.

DESIGN

Data were pooled from six 12-week, phase III-IV clinical studies in adults who received prucalopride (1 or 2 mg once daily) or placebo for CIC.

METHODS

Adults were stratified by age (<50; 50-64; ⩾65 years), BMI (underweight/healthy weight, <25 kg/m; overweight, 25 to <30 kg/m; obese, ⩾30 kg/m), and renal function (normal renal function, estimated glomerular filtration rate (eGFR) ⩾90 mL/min/1.73 m; mild renal impairment, eGFR 60 to <90 mL/min/1.73 m; moderate renal impairment, eGFR 30 to <60 mL/min/1.73 m). The primary efficacy endpoint was the proportion of patients with a mean of ⩾3 complete spontaneous bowel movements/week over 12 weeks. Safety data were evaluated descriptively.

RESULTS

Of 2484 patients stratified by age (prucalopride, = 1237; placebo, = 1247), 1402, 708, and 374 were aged <50, 50-64, and ⩾65 years, respectively. Of 2482 patients stratified by BMI (prucalopride, = 1237; placebo, = 1245), 1425, 713, and 344 were underweight/healthy weight, overweight, and obese, respectively. Of 2474 patients stratified by renal function (prucalopride, = 1233; placebo, = 1241), 1444, 869, and 161 had normal renal function, mild renal impairment, and moderate renal impairment, respectively. More prucalopride-treated than placebo-treated patients achieved the primary efficacy endpoint. The difference was significant for all subgroups, except for the obese and moderate renal impairment subgroups. More prucalopride-treated than placebo-treated patients reported treatment-related adverse events in most subgroups.

CONCLUSION

Prucalopride demonstrated efficacy in adults with CIC, irrespective of age, BMI, and renal function. No unexpected safety concerns were identified.

TRIAL REGISTRATION

ClinicalTrials.gov identifiers (https://clinicaltrials.gov/): NCT01147926, NCT01424228, NCT01116206, NCT00483886, NCT00485940, NCT00488137.

背景

普芦卡必利（每日一次，1或2毫克）已被批准用于治疗患有慢性特发性便秘（CIC）的成人患者。

目的

我们确定了年龄、体重指数（BMI）和肾功能对普芦卡必利治疗CIC成人患者的疗效和安全性的影响。

设计

数据来自六项为期12周的III-IV期临床研究，这些研究中的成人患者接受了普芦卡必利（每日一次，1或2毫克）或安慰剂治疗CIC。

方法

成人患者按年龄（<50岁；50 - 64岁；≥65岁）、BMI（体重过轻/健康体重，<25kg/m²；超重，25至<30kg/m²；肥胖，≥30kg/m²）和肾功能（肾功能正常，估计肾小球滤过率（eGFR）≥90mL/min/1.73m²；轻度肾功能损害，eGFR 60至<90mL/min/1.73m²；中度肾功能损害，eGFR 30至<60mL/min/1.73m²）进行分层。主要疗效终点是在12周内平均每周至少有3次完全自主排便的患者比例。对安全性数据进行了描述性评估。

结果

在按年龄分层的2484例患者中（普芦卡必利组，n = 1237；安慰剂组，n = 1247），分别有1402例、708例和374例患者年龄<50岁、50 - 64岁和≥65岁。在按BMI分层的2482例患者中（普芦卡必利组，n = 1237；安慰剂组，n = 1245），分别有1425例、713例和344例患者体重过轻/健康体重、超重和肥胖。在按肾功能分层的2474例患者中（普芦卡必利组，n = 1233；安慰剂组，n = 1241），分别有1444例、869例和161例患者肾功能正常、轻度肾功能损害和中度肾功能损害。与接受安慰剂治疗的患者相比，接受普芦卡必利治疗的患者更多地达到了主要疗效终点。除肥胖和中度肾功能损害亚组外，所有亚组的差异均具有显著性。在大多数亚组中，与接受安慰剂治疗的患者相比，接受普芦卡必利治疗的患者报告的治疗相关不良事件更多。