中度至重度溃疡性结肠炎患者的基线肠外表现及托法替布的疗效
Extraintestinal manifestations at baseline, and the effect of tofacitinib, in patients with moderate to severe ulcerative colitis.
作者信息
Rubin David T, Reinisch Walter, Greuter Thomas, Kotze Paulo G, Pinheiro Marcia, Mundayat Rajiv, Maller Eric, Fellmann Marc, Lawendy Nervin, Modesto Irene, Vavricka Stephan R, Lichtenstein Gary R
机构信息
University of Chicago Medicine, Inflammatory Bowel Disease Center, 5841 S. Maryland Avenue, MC4076, Chicago, IL 60637, USA.
Medical University of Vienna, Vienna, Austria.
出版信息
Therap Adv Gastroenterol. 2021 May 16;14:17562848211005708. doi: 10.1177/17562848211005708. eCollection 2021.
INTRODUCTION
Extraintestinal manifestations (EIMs) in patients with ulcerative colitis (UC) are common. Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. We evaluated the efficacy of tofacitinib in patients with EIMs, and the impact of tofacitinib on EIMs in patients with UC in the OCTAVE clinical program.
METHODS
Data from two 8-week induction studies (OCTAVE Induction 1 and 2) and a 52-week maintenance study (OCTAVE Sustain) were analyzed. The effect of tofacitinib on efficacy outcomes stratified by EIM status, proportion of predefined prior and active EIMs at baseline, and change from baseline in EIMs were determined at the end of the treatment period (weeks 8 or 52), or at early termination.
RESULTS
At baseline of OCTAVE Induction 1 and 2, and OCTAVE Sustain, 27.0% and 9.0% of patients had a history of EIMs (prior or active), respectively. Patients treated with tofacitinib 10 mg twice daily (BID) achieved remission and had endoscopic improvement in all studies, irrespective of any history of EIMs. A greater proportion of patients had active peripheral arthritis at baseline of OCTAVE Induction 1 and 2 OCTAVE Sustain. In OCTAVE Induction 1 and 2, similar proportions of tofacitinib and placebo-treated patients with active peripheral arthritis experienced either no change (81.3% and 85.7%, respectively) or an improvement (15.6% and 14.3%, respectively). By week 52 of OCTAVE Sustain, improvements in active peripheral arthritis were only observed in tofacitinib-treated patients (16.7% and 33.3% with tofacitinib 5 and 10 mg BID, respectively).
CONCLUSION
Any history of EIMs did not influence the efficacy of tofacitinib 10 mg BID for induction or maintenance of UC. The most common active EIM was peripheral arthritis, for which many patients in OCTAVE Induction 1 and 2, and OCTAVE Sustain, reported improvement or no change from baseline with tofacitinib treatment.Clinicaltrials.gov:NCT01465763; NCT01458951; NCT01458574.
引言
溃疡性结肠炎（UC）患者的肠外表现（EIMs）很常见。托法替布是一种口服小分子Janus激酶抑制剂，用于治疗UC。我们在OCTAVE临床项目中评估了托法替布对EIMs患者的疗效，以及托法替布对UC患者EIMs的影响。
方法
分析了两项为期8周的诱导研究（OCTAVE诱导1和2）和一项为期52周的维持研究（OCTAVE维持）的数据。在治疗期结束时（第8周或第52周）或提前终止时，确定托法替布对按EIM状态分层的疗效结果、基线时预先定义的既往和活动性EIMs的比例以及EIMs相对于基线的变化的影响。
结果
在OCTAVE诱导1和2以及OCTAVE维持的基线时，分别有27.0%和9.0%的患者有EIMs病史（既往或活动性）。在所有研究中，每天两次服用10 mg托法替布的患者均实现缓解并在内镜检查方面有所改善，无论其是否有EIMs病史。在OCTAVE诱导1和2以及OCTAVE维持的基线时，有更高比例的患者患有活动性外周关节炎。在OCTAVE诱导1和2中，接受托法替布和安慰剂治疗的活动性外周关节炎患者中，比例相似的患者病情无变化（分别为81.3%和85.7%）或有所改善（分别为15.6%和14.3%）。到OCTAVE维持的第52周时，仅在接受托法替布治疗的患者中观察到活动性外周关节炎有所改善（每天两次服用5 mg和10 mg托法替布的患者分别为16.7%和33.3%）。
结论
任何EIMs病史均不影响每天两次服用10 mg托法替布诱导或维持UC的疗效。最常见的活动性EIM是外周关节炎，在OCTAVE诱导1和2以及OCTAVE维持中，许多患者报告托法替布治疗后相对于基线有所改善或无变化。Clinicaltrials.gov：NCT01465763；NCT01458951；NCT01458574。
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