Abstract

Background

Tofacitinib is an oral Janus kinase inhibitor recently approved to induce and maintain remission in ulcerative colitis (UC).

Aims

Considering the number of anti-TNF non-responders, this study aims to assess the effectiveness and safety of tofacitinib in a cohort of multi-failure patients with moderate-to-severe UC at 52 weeks.

Methods

From January 2021 to March 2023, we performed a prospective multicenter study observing adult patients with moderate-to-severe UC starting tofacitinib after an anti-TNF failure for a 52-week-long period. Effectiveness and safety were assessed in terms of colectomy rate, clinical remission and response, endoscopic remission, steroid-free clinical remission, and rate of adverse events.

Results

We included 58 patients with UC with an age of 42 ± 14.4 years, 59% males, 96.6% left-sided or pancolitis, who were failure to a single (65.5%) or more than one anti-TNF (34.5%). Only 6 (10.3%) patients underwent colectomy. Colectomy was clinically associated with the necessity and the number of extra cycles of tofacitinib 10 mg bid at W8 (p = 0.023) and W24 (p = 0.004), and with a higher partial Mayo score at W8 (p = 0.025). At W52, clinical remission, clinical response, and steroid-free clinical remission were 53.4%, 43.1%, and 48.3%, respectively. Of 22 performed colonoscopies at W52, 11 (50%) showed endoscopic remission. Adverse events occurred in 14 (24.1%) patients, but only 2 (3.4%) led to tofacitinib discontinuation.

Conclusions

In a real-life setting of patients with anti-TNF refractory UC, tofacitinib has proved to be effective in preventing colectomy and inducing clinical and endoscopic remission at 52 weeks with a good safety profile.

中文翻译：

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托法替布对抗 TNF 难治性溃疡性结肠炎一年结肠切除术风险的影响：一项意大利前瞻性多中心研究

摘要

背景

托法替布是一种口服 Janus 激酶抑制剂，最近被批准用于诱导和维持溃疡性结肠炎 (UC) 的缓解。

目标

考虑到抗 TNF 无反应者的数量，本研究旨在评估托法替布在 52 周时中重度 UC 多次失败患者队列中的有效性和安全性。

方法

从2021年1月到2023年3月，我们进行了一项前瞻性多中心研究，观察中重度UC成年患者在抗TNF治疗失败后开始托法替布治疗52周的情况。从结肠切除率、临床缓解和反应、内镜缓解、无类固醇临床缓解和不良事件发生率等方面评估有效性和安全性。

结果

我们纳入了 58 名 UC 患者，年龄为 42 ± 14.4 岁，其中 59% 为男性，96.6% 为左侧结肠炎或全结肠炎，他们对单一 (65.5%) 或一种以上抗 TNF (34.5%) 治疗失败。只有 6 名（10.3%）患者接受了结肠切除术。结肠切除术在临床上与第 8 周 ( p  = 0.023) 和第 24 周 ( p = 0.004)托法替尼 10 mg bid 的必要性和额外周期数相关 ，并且与第 8 周较高的部分 Mayo 评分相关 ( p  = 0.025)。第 52 周时，临床缓解率、临床缓解率和无类固醇临床缓解率分别为 53.4%、43.1% 和 48.3%。在第 52 周时进行的 22 例结肠镜检查中，11 例 (50%) 显示内镜缓解。 14 名患者 (24.1%) 发生不良事件，但只有 2 名患者 (3.4%) 导致托法替布停药。

结论

在抗 TNF 难治性 UC 患者的现实生活中，托法替布已被证明可有效预防结肠切除术并在 52 周时诱导临床和内镜缓解，且安全性良好。