Vermeire Séverine, Feagan Brian G, Peyrin-Biroulet Laurent, Oortwijn Alessandra, Faes Margaux, de Haas Angela, Rogler Gerhard
Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.
Alimentiv Inc., London, Ontario, Canada.
J Crohns Colitis. 2024 Jan 27;18(1):54-64. doi: 10.1093/ecco-jcc/jjad123.
Maintenance treatment for ulcerative colitis may be discontinued for multiple reasons. This post hoc analysis assessed the efficacy and safety of re-treatment with filgotinib, an oral, once-daily, Janus kinase 1 preferential inhibitor, in the phase 2b/3 SELECTION trial and its long-term extension [LTE] study in ulcerative colitis.
Partial Mayo Clinic Score [pMCS] response and remission were evaluated in patients who received induction with filgotinib 200 mg [FIL200] or 100 mg [FIL100], were randomized to treatment withdrawal [placebo] during maintenance, and following disease worsening, were re-treated with open-label FIL200 in the LTE study. Factors were evaluated for association with pMCS remission at LTE week 12, and safety outcomes were reported.
Analyses included 86 patients [FIL200: n = 51; FIL100: n = 35]. Median time to disease worsening following treatment withdrawal was 15.1 weeks (95% confidence interval [CI]: 9.1-18.7) for FIL200-induced patients and 9.6 weeks [95% CI: 6.3-12.0] for FIL100-induced patients. Three-quarters [75%] of patients achieved a pMCS response within 4-5 weeks of re-treatment in both groups. At LTE week 48, pMCS remission was achieved by 45.1% and 51.4% of FIL200- and FIL100-induced patients, respectively. Factors independently associated with restoring efficacy included no concomitant use of corticosteroids at induction baseline, and high albumin levels, pMCS remission, and endoscopic score at maintenance baseline. No new safety signals were reported among re-treated patients.
In induction responders, re-treatment with FIL200 following temporary withdrawal from therapy restores response and/or remission in the majority of patients within 12 weeks. Re-treatment is well-tolerated. ClinicalTrials.gov identifiers: NCT02914522, NCT02914535.
溃疡性结肠炎的维持治疗可能因多种原因而中断。这项事后分析评估了在2b/3期SELECTION试验及其溃疡性结肠炎长期扩展[LTE]研究中，使用每日一次口服的Janus激酶1优先抑制剂非戈替尼重新治疗的疗效和安全性。
对接受200mg非戈替尼[FIL200]或100mg[FIL100]诱导治疗、在维持期随机接受撤药治疗（安慰剂）、疾病恶化后在LTE研究中接受开放标签FIL200重新治疗的患者，评估部分梅奥诊所评分[pMCS]反应和缓解情况。评估与LTE第12周时pMCS缓解相关的因素，并报告安全性结果。
分析纳入86例患者[FIL200组：n = 51；FIL100组：n = 35]。FIL200诱导治疗的患者在撤药后疾病恶化的中位时间为15.1周（95%置信区间[CI]：9.1 - 18.7），FIL100诱导治疗的患者为9.6周[95%CI：6.3 - 12.0]。两组中四分之三（75%）的患者在重新治疗后4 - 5周内达到pMCS反应。在LTE第48周时，FIL200和FIL100诱导治疗的患者分别有45.1%和51.4%实现了pMCS缓解。与恢复疗效独立相关的因素包括诱导基线时未同时使用皮质类固醇、维持基线时白蛋白水平高、pMCS缓解和内镜评分。重新治疗的患者中未报告新的安全信号。
在诱导治疗有反应的患者中，在暂时停药后用FIL200重新治疗可使大多数患者在12周内恢复反应和/或缓解。重新治疗耐受性良好。ClinicalTrials.gov标识符：NCT02914522，NCT02914535。
