托法替布与乌帕替尼治疗急性重度溃疡性结肠炎的疗效比较

Comparative effectiveness of tofacitinib versus upadacitinib for the treatment of acute severe ulcerative colitis.

作者信息

Honap Sailish, St-Pierre Joelle, Colwill Michael, Patel Kamal, Le Berre Catherine, Caron Bénédicte, Nogami Akira, Kobayashi Taku, Altwegg Romain, Laharie David, Hebuterne Xavier, Nachury Maria, Roblin Xavier, Uzzan Mathieu, Kotze Paulo Gustavo, Lukáš Milan, Vieujean Sophie, D'Amico Ferdinando, Albshesh Ahmad, Guillo Lucas, Fumery Mathurin, Nancey Stephane, Ye Byong Duk, Bergemalm Daniel, Halfvarson Jonas, Buisson Anthony, Karmiris Konstantinos, Rubin David, Vicaut Eric, Peyrin-Biroulet Laurent

机构信息

School of Immunology and Microbial Sciences, King's College London, UK; Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK.

Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.

出版信息

Clin Gastroenterol Hepatol. 2025 Jul 26. doi: 10.1016/j.cgh.2025.07.025.

DOI:10.1016/j.cgh.2025.07.025

PMID:40721074

Abstract

BACKGROUND AND AIMS

Tofacitinib and upadacitinib are Janus kinase (JAK) inhibitors that are increasingly used for the treatment of acute severe ulcerative colitis (ASUC). However, comparative analyses of safety and effectiveness have not been performed for their use in this setting.

METHODS

This multicenter, retrospective study enrolled hospitalized adult patients treated with tofacitinib or upadacitinib for ASUC between January 2019 and June 2024. The main outcomes were clinical response, clinical remission, and colectomy-free survival. Propensity-adjusted analyses using inverse probability treatment weighting (IPTW), and double robust estimations (DRE) were used to control for confounding factors.

RESULTS

In total, 111 patients (60 tofacitinib, 51 upadacitinib) were enrolled across 23 international centers. JAK inhibitors were used to induce response in 86 (77%) patients and used to maintain response after adequate intravenous steroid response in 25 (23%). The median follow up was 31 weeks (IQR 13-64). Between days 3-7 after treatment initiation, upadacitinib was associated with greater response rates 84% vs.54%,p=0.02 but response/remission were comparable at day 98 (45%/36% vs 55/48%) and day 182 (29/29% vs. 39/34%). Sub-analyses for JAK inhibitor use as salvage therapy (tofacitinib (n=35) vs. upadacitinib (n=31)) showed similar effectiveness outcomes across both groups. The probabilities of colectomy-free survival at days 98/182 for tofacitinib and upadacitinib were 79%/75% and 80%/78%, respectively, with no significant differences in the comparison of survival curves, p=0.99. Treatment failure rates (where JAK inhibitor was used to maintain remission) were similar at days 98 and 182. The frequency of adverse events was comparable.

CONCLUSION

Tofacitinib and upadacitinib appear to have similar effectiveness and safety profiles when used for the treatment of ASUC.

摘要

背景与目的

托法替布和乌帕替尼是越来越多地用于治疗急性重度溃疡性结肠炎（ASUC）的 Janus 激酶（JAK）抑制剂。然而，尚未对它们在这种情况下使用的安全性和有效性进行比较分析。

方法

这项多中心回顾性研究纳入了 2019 年 1 月至 2024 年 6 月期间因 ASUC 接受托法替布或乌帕替尼治疗的住院成年患者。主要结局为临床缓解、临床缓解和无结肠切除术生存率。使用逆概率处理加权（IPTW）和双重稳健估计（DRE）进行倾向调整分析，以控制混杂因素。

结果

总共 111 名患者（60 名使用托法替布，51 名使用乌帕替尼）在 23 个国际中心入组。JAK 抑制剂用于诱导缓解 86 例（77%）患者，并在充分静脉使用类固醇缓解后用于维持缓解 25 例（23%）。中位随访时间为 31 周（IQR 13 - 64）。在治疗开始后第 3 - 7 天，乌帕替尼的缓解率更高，分别为 84% 对 54%，p = 0.02，但在第 98 天（45%/36% 对 55/48%）和第 182 天（29/29% 对 39/34%）时缓解/缓解情况相当。将 JAK 抑制剂用作挽救疗法的亚组分析（托法替布（n = 35）对乌帕替尼（n = 31））显示两组的有效性结果相似。托法替布和乌帕替尼在第 98/182 天的无结肠切除术生存率概率分别为 79%/75% 和 80%/78%，生存曲线比较无显著差异，p = 0.99。在第 98 天和第 182 天，治疗失败率（使用 JAK 抑制剂维持缓解的情况）相似。不良事件发生频率相当。