当前位置:科学网首页 > 小柯机器人 >详情
乌帕替尼诱导和维持治疗中重度克罗恩病患者疗效显著
作者:小柯机器人 发布时间:2023/5/31 16:17:39

美国西奈山伊坎医学院Jean-Frederic Colombel团队研究了乌帕替尼诱导和维持治疗克罗恩病的疗效。相关论文发表在2023年5月24日出版的《新英格兰医学杂志》上。

乌帕替尼是一种口服选择性Janus激酶(JAK)抑制剂,目前正在研究用于治疗克罗恩病。

在两项3期诱导试验(U-EXCEL和U-EXCEED)中,研究组随机分配中重度克罗恩病患者接受45 mg乌帕替尼或安慰剂(2:1比例),每天一次,持续12周。在U-ENDURE维持试验中,对乌帕替尼诱导治疗有临床反应的患者被随机分配接受15 mg乌帕替尼、30 mg乌帕替尼或安慰剂(1:1:1比例),每天一次,持续52周。

诱导(第12周)和维持(第52周)的主要终点是临床缓解(定义为克罗恩病活动指数评分<150[范围,0-600,评分越高表示疾病活动越严重])和内镜缓解(定义为克罗恩病简单内镜评分降低[SES-CD;范围为0至56,得分越高,表示疾病越严重],比诱导试验的基线水平>50%[或对于基线水平SES-CD为4的患者,比基线水平降低≥2分])。

共有526名患者在U-EXCEL中接受了随机分组,495名在U-EXCED中接受了随机化分组,502名在U-ENDURE中接受了分组。接受45 mg乌帕替尼治疗的患者临床缓解率(U-EXCEL中,49.5%对29.1%;U-EXCED中,38.9%对21.1%)和内镜缓解率(U-EXCEL中,45.5%对13.1%;U-EXCEED中,34.6%对3.5%)明显高于接受安慰剂治疗的患者(所有比较均<0.001)。

在U-ENDURE的第52周,服用15 mg乌帕替尼(37.3%)或30 mg乌帕替尼(47.6%)的患者临床缓解率高于安慰剂(15.1%),服用15 mg乌帕替尼(27.6%)或30 mg乌帕提尼(40.1%)的患者内镜缓解率也高于安慰剂(7.3%)(所有比较均<0.001)。45 mg和30 mg乌帕替尼组的带状疱疹感染发生率高于相应的安慰剂组,30 mg乌帕替尼组的肝脏疾病和中性粒细胞减少症发生率高于其他维持组。4名接受45 mg乌帕替尼治疗的患者、1名接受30 mg或15 mg乌帕替尼治疗的患者出现胃肠穿孔。

研究结果表明,在中重度克罗恩病患者中,乌帕替尼诱导和维持治疗优于安慰剂。

附:英文原文

Title: Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease

Author: Edward V. Loftus, Jr., M.D.,, Julian Panés, M.D.,, Ana P. Lacerda, M.D.,, Laurent Peyrin-Biroulet, M.D., Ph.D.,, Geert D’Haens, M.D.,, Remo Panaccione, M.D.,, Walter Reinisch, M.D.,, Edouard Louis, M.D., Ph.D.,, Minhu Chen, M.D.,, Hiroshi Nakase, M.D.,, Jakob Begun, M.D.,, Brigid S. Boland, M.D.,, Charles Phillips, M.D.,, Mohamed-Eslam F. Mohamed, Ph.D.,, Jianzhong Liu, M.D.,, Ziqian Geng, Ph.D.,, Tian Feng, Ph.D.,, Elena Dubcenco, M.D.,, and Jean-Frederic Colombel, M.D.

Issue&Volume: 2023-05-24

Abstract:

Background

Upadacitinib, an oral selective Janus kinase (JAK) inhibitor, is under investigation for the treatment of Crohn’s disease.

Methods

In two phase 3 induction trials (U-EXCEL and U-EXCEED), we randomly assigned patients with moderate-to-severe Crohn’s disease to receive 45 mg of upadacitinib or placebo (2:1 ratio) once daily for 12 weeks. Patients who had a clinical response to upadacitinib induction therapy were randomly assigned in the U-ENDURE maintenance trial to receive 15 mg of upadacitinib, 30 mg of upadacitinib, or placebo (1:1:1 ratio) once daily for 52 weeks. The primary end points for induction (week 12) and maintenance (week 52) were clinical remission (defined as a Crohn’s Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]) and endoscopic response (defined as a decrease in the Simple Endoscopic Score for Crohn’s Disease [SES-CD; range, 0 to 56, with higher scores indicating more severe disease] of >50% from baseline of the induction trial [or for patients with an SES-CD of 4 at baseline, a decrease of ≥2 points from baseline]).

Results

A total of 526 patients underwent randomization in U-EXCEL, 495 in U-EXCEED, and 502 in U-ENDURE. A significantly higher percentage of patients who received 45-mg upadacitinib than those who received placebo had clinical remission (in U-EXCEL, 49.5% vs. 29.1%; in U-EXCEED, 38.9% vs. 21.1%) and an endoscopic response (in U-EXCEL, 45.5% vs. 13.1%; in U-EXCEED, 34.6% vs. 3.5%) (P<0.001 for all comparisons). At week 52 in U-ENDURE, a higher percentage of patients had clinical remission with 15-mg upadacitinib (37.3%) or 30-mg upadacitinib (47.6%) than with placebo (15.1%), and a higher percentage had an endoscopic response with 15-mg upadacitinib (27.6%) or 30-mg upadacitinib (40.1%) than with placebo (7.3%) (P<0.001 for all comparisons). Herpes zoster infections occurred more frequently in the 45-mg and 30-mg upadacitinib groups than in the respective placebo groups, and hepatic disorders and neutropenia were more frequent in the 30-mg upadacitinib group than in the other maintenance groups. Gastrointestinal perforations developed in 4 patients who received 45-mg upadacitinib and in 1 patient each who received 30-mg or 15-mg upadacitinib.

Conclusions

Upadacitinib induction and maintenance treatment was superior to placebo in patients with moderate-to-severe Crohn’s disease.

DOI: 10.1056/NEJMoa2212728

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2212728

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:176.079
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home