托法替布治疗抗 TNF 难治性溃疡性直肠炎患者：GETAID 的一项多中心队列研究。

Tofacitinib for Patients with Anti-TNF Refractory Ulcerative Proctitis: A Multicentre Cohort Study from the GETAID.

机构信息

University of Lille, CHU Lille, Institute for Translational Research in Inflammation, Lille, France.

Department of Gastroenterology, Hopital Beaujon, Universite de Paris, France.

出版信息

J Crohns Colitis. 2024 Mar 1;18(3):424-430. doi: 10.1093/ecco-jcc/jjad169.

DOI:10.1093/ecco-jcc/jjad169

PMID:37796025

Abstract

BACKGROUND

Although ulcerative proctitis [UP] can dramatically impair quality of life, treatment efficacy has been poorly investigated in UP as it was historically excluded from phase 2/3 randomised controlled trials in ulcerative colitis. Our aim was to assess the effectiveness and safety of tofacitinib for the treatment of UP.

METHODS

We conducted a retrospective, multicentre study in 17 GETAID centres, including consecutive patients with UP treated with tofacitinib. The primary endpoint was steroid-free remission between Week 8 and Week 14, defined as a partial Mayo score of 2 [and no individual subscore above 1]. Secondary outcomes included clinical response and steroid-free remission after induction and at 1 year.

RESULTS

All the 35 enrolled patients previously received anti-tumour necrosis factor [TNF] therapy and 88.6% were exposed to at least two lines of biologics. At baseline, the median partial Mayo score was 7 (intequartile range [IQR] [5.5-7]). After induction [W8-W14], 42.9% and 60.0% of patients achieved steroid-free remission and clinical response, respectively. At 1 year, the steroid-free clinical remission and clinical response rates were 39.4% and 45.5%, respectively, and 51.2% [17/33] were still receiving tofacitinib treatment. Survival without tofacitinib withdrawal was estimated at 50.4% (95% confidence interval [CI] [35.5-71.6]) at 1 year. Only a lower partial Mayo at baseline was independently associated with remission at induction (0dds ratio [OR] = 0.56 for an increase of 1, (95% CI [0.33-0.95], p = 0.03). Five [14.3%] adverse events were reported, with one leading to treatment withdrawal [septic shock secondary to cholecystitis].

CONCLUSION

Tofacitinib may offer a therapeutic option for patients with refractory UP.

摘要

背景

虽然溃疡性直肠炎[UP]会显著降低生活质量，但由于历史上溃疡性结肠炎的 2/3 期随机对照试验将其排除在外，因此 UP 的治疗效果尚未得到充分研究。我们的目的是评估托法替尼治疗 UP 的有效性和安全性。

方法

我们在 17 个 GETAID 中心进行了一项回顾性、多中心研究，纳入了接受托法替尼治疗的 UP 连续患者。主要终点是在第 8 周到第 14 周之间无类固醇缓解，定义为部分 Mayo 评分为 2[且各单项评分均不高于 1]。次要结局包括诱导后和 1 年时的临床缓解和无类固醇缓解。

结果

所有 35 名入组患者均曾接受过抗肿瘤坏死因子[TNF]治疗，88.6%的患者至少接受过两种生物制剂治疗。基线时，部分 Mayo 评分中位数为 7（四分位间距[IQR] [5.5-7]）。诱导后[第 8 周到第 14 周]，42.9%和 60.0%的患者分别达到无类固醇缓解和临床缓解。1 年后，无类固醇临床缓解率和临床缓解率分别为 39.4%和 45.5%，51.2%（33/64）仍在接受托法替尼治疗。1 年时无托法替尼停药的生存率估计为 50.4%（95%置信区间[CI] [35.5-71.6]）。只有基线时较低的部分 Mayo评分与诱导缓解独立相关（增加 1 分的优势比[OR]为 0.56（95%CI [0.33-0.95]，p=0.03）。报告了 5 例[14.3%]不良事件，其中 1 例导致治疗中止[胆囊炎继发感染性休克]。