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在有和没有先前接触抗肿瘤坏死因子α抗体的溃疡性结肠炎患者中,Janus激酶抑制剂的倾向评分匹配真实世界比较治疗结果。

Propensity score-matched real-world comparative treatment outcomes of Janus kinase inhibitors for ulcerative colitis in patients with and without prior exposure to anti-tumor necrosis factor α antibody.

作者信息

Ikenouchi Maiko, Fukui Hirokazu, Yagi Soichi, Nogami Akira, Kaku Koji, Sato Toshiyuki, Kawai Mikio, Kamikozuru Koji, Yokoyama Yoko, Takagawa Tetsuya, Tomita Toshihiko, Kobayashi Taku, Shinzaki Shinichiro

机构信息

Department of Gastroenterology, Faculty of Medicine, Hyogo Medical University, Hyogo, Japan.

Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.

出版信息

Intest Res. 2025 Feb 3. doi: 10.5217/ir.2024.00148.

DOI:10.5217/ir.2024.00148
PMID:39894450
Abstract

BACKGROUND/AIMS: Tofacitinib (TFB), filgotinib (FIL), and upadacitinib (UPA) are Janus kinase (JAK) inhibitors approved for moderate-to-severe ulcerative colitis (UC). The appropriate positioning of each JAK inhibitor in the treatment algorithm, however, is unclear. Furthermore, real-world efficacy of JAK inhibitors for patients with UC and prior anti-tumor necrosis factor α antibody (aTNF) treatment are not fully investigated. We compared the efficacy and safety of 3 JAK inhibitors in patients with UC, considering their prior aTNF exposure.

METHODS

A retrospective study was conducted in patients with UC who started TFB, FIL, or UPA at 2 academic centers. This propensity score-matched cohort study assessed the effectiveness of the 3 JAK inhibitors for UC in patients with and without prior aTNF exposure, comparing steroid-free clinical remission and response rates after 8 weeks.

RESULTS

Among 274 patients who met the inclusion criteria, 145 experienced aTNF exposure (TFB: 59.2%, 100/169; FIL: 34.5%, 20/58; UPA: 53.2%, 25/47). Based on propensity score-matching, UPA led to a higher steroid-free clinical remission rates than TFB (adjusted odds ratio [aOR], 5.57; 95% confidence interval [CI], 1.42-21.90) or FIL (aOR, 9.00; 95% CI, 1.42-57.10) in patients exposed to aTNF. Steroid-free clinical remission and clinical response rates did not differ significantly between each group in patients non-exposed to aTNF. The incidence of adverse events was slightly higher with UPA than TFB or FIL.

CONCLUSIONS

UPA may be more effective for UC than TFB or FIL, especially in patients with previous aTNF exposure, although consideration should be given to adverse events.

摘要

背景/目的:托法替布(TFB)、非戈替尼(FIL)和乌帕替尼(UPA)是已被批准用于中重度溃疡性结肠炎(UC)的 Janus 激酶(JAK)抑制剂。然而,每种 JAK 抑制剂在治疗方案中的合适定位尚不清楚。此外,JAK 抑制剂对 UC 患者及既往接受抗肿瘤坏死因子α抗体(aTNF)治疗患者的真实疗效尚未得到充分研究。我们比较了 3 种 JAK 抑制剂在 UC 患者中的疗效和安全性,并考虑了他们既往 aTNF 暴露情况。

方法

对在 两个学术中心开始使用 TFB、FIL 或 UPA 的 UC 患者进行了一项回顾性研究。这项倾向评分匹配队列研究评估了 3 种 JAK 抑制剂对有或无既往 aTNF 暴露的 UC 患者的有效性,比较了 8 周后无激素临床缓解率和缓解率。

结果

在 274 名符合纳入标准的患者中,145 名有 aTNF 暴露史(TFB:59.2%,100/169;FIL:34.5%,20/58;UPA:53.2%,25/47)。基于倾向评分匹配,在有 aTNF 暴露的患者中,UPA 导致的无激素临床缓解率高于 TFB(调整优势比[aOR],5.57;95%置信区间[CI],1.42 - 21.90)或 FIL(aOR,9.00;95%CI,1.42 - 57.10)。在无 aTNF 暴露的患者中,每组之间的无激素临床缓解率和临床缓解率没有显著差异。UPA 的不良事件发生率略高于 TFB 或 FIL。

结论

UPA 对 UC 可能比 TFB 或 FIL 更有效,尤其是在既往有 aTNF 暴露的患者中,尽管应考虑不良事件。

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