2次JAKi治疗UC值得吗?英国多中心回顾性研究。

IF 8.7
Chandni Radia, Yaa Danso, Susan Ritchie, Melissa Hale, Alexander T Elford, Chirag Patel, Lucy Hicks, Sonia Kalyanji, Chaonan Dong, Katie Yeung, Jie Han Yeo, Mohammed Allah-Ditta, Maria Bishara, Karishma Sethi-Arora, Lushen Pillay, Emma L Johnston, Ruth Rudling, Fiona Rees, Philip Harvey, Hannah Trodden-Mittnacht, Emma Davis, Aileen Fraser, Nitish Jivan Sawan, Muhammad Azhar Hussain, Roisin Campbell, Becky George, Megan Rawcliffe, Xin Yi Choon, Krishna Shah, Dania Al-Zarrad, Jennifer Toft, Puneet Chhabra, Nick Burr, Alice Hewitt, Rohith Kumar, Sara McCartney, Konstantina Rosiou, Anjan Dhar, Charlie W Lees, Christopher A Lamb, Ally Speight, Tariq Ahmad, Jimmy Limdi, Tim Raine, Alissa Walsh, Rachel Cooney, Paul Harrow, Kamal Patel, Mark Samaan, Polychronis Pavlidis, Alexandra Kent, Christian Selinger, Klaartje Kok
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引用次数: 0

摘要

背景和目的:Janus激酶抑制剂(JAKi)是治疗溃疡性结肠炎(UC)的有效药物,但经常发生反应不足(IR)或不耐受。本研究旨在评估二次JAKi在现实世界UC队列中的有效性。方法:对英国19家医院进行回顾性多中心队列研究。根据现有评估,主要结局是第8周和第24周的临床缓解(单纯临床结肠炎活动指数/部分梅奥评分≤1)。同时评估生化(CRP≤5mg/L,粪钙保护蛋白≤200µg/g)和内镜(溃疡性结肠炎内镜严重程度指数/Mayo内镜评分≤1)缓解情况。结果:131例活动性UC患者入选。大多数(60%)接受过3种以上的先进治疗,50%在诱导时需要皮质类固醇。第8周和第24周的临床缓解率分别为59%和51%。第8周生化缓解率和内镜缓解率分别为61%和60%,第24周分别为47%和32%。所有疾病活动性参数在第8周显著降低(p)。结论:在这个高度难治性UC患者中,第二次JAKi在第一次JAKi的IR后有效缓解。首次JAKi失败的类型似乎不影响临床缓解。没有发现新的安全信号。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Is 2nd JAKi treatment for UC worth the effort? A retrospective, multi-Centre UK study.

Background and aims: Janus Kinase inhibitors (JAKi) provide effective treatment for ulcerative colitis (UC), but inadequate response (IR) or intolerance occurs frequently. This study aimed to assess effectiveness of a second JAKi in a real-world UC cohort.

Methods: A retrospective multicentre cohort study encompassing 19 UK hospitals was undertaken. Primary outcome was clinical remission (Simple Clinical Colitis Activity Index/partial Mayo Score ≤ 1) at weeks 8 and 24, based on available assessments. Biochemical (CRP ≤ 5mg/L and faecal calprotectin ≤ 200µg/g) and endoscopic (Ulcerative Colitis Endoscopic Index of Severity/Mayo Endoscopic Subscore ≤ 1) remission were also assessed.

Results: 131 patients with active UC were included. Majority (60%) had exposure to ≥ 3 advanced therapies and 50% required corticosteroids at induction. Clinical remission rates were 59% and 51% at weeks 8 and 24. Biochemical and endoscopic remission rates were 61% and 60% at week 8 and 47% and 32% at week 24. All disease activity parameters significantly reduced by week 8 (p < 0.001). At week 24 no difference was detected in clinical remission rates between those with primary non-response (42%) or secondary loss of response (52%) to their first JAKi (p = 0.518). Clinical remission did not differ between upadacitinib (54%) and filgotinib (36%), p = 0.253. Adverse events occurred in 27% of patients, and serious adverse events in 8%.

Conclusions: In this highly refractory cohort with active UC a second JAKi effectively achieved remission following IR to first JAKi. Type of first JAKi failure did not appear to influence clinical remission. No new safety signals were found.

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