Alimentiv Inc., London, Ontario, Canada.
Western University, London, Ontario, Canada.
Aliment Pharmacol Ther. 2024 Sep;60(5):563-584. doi: 10.1111/apt.18158. Epub 2024 Jul 31.
Filgotinib, an oral, once-daily, Janus kinase 1 preferential inhibitor, is an approved treatment for moderately to severely active ulcerative colitis.
The aim of this study is to assess the safety and efficacy of continued filgotinib therapy over ~4 years in the long-term extension of the phase 2b/3 SELECTION trial (SELECTIONLTE; NCT02914535).
In this interim analysis of SELECTIONLTE, SELECTION completers (week 10 responders to filgotinib who completed the maintenance study) continued their assigned treatment (double-blind filgotinib 200 mg [FIL200] or filgotinib 100 mg) and SELECTION week 10 non-responders received open-label FIL200. We assessed safety by adverse events (AEs), and efficacy by partial Mayo Clinic Score (pMCS), inflammatory biomarkers and health-related quality of life (HRQoL). We compared safety and efficacy between achievers and non-achievers of a multi-component endpoint, comprehensive disease control (CDC), comprising symptomatic, endoscopic, inflammatory biomarker and HRQoL improvements.
Data for completers (n = 250) and non-responders (n = 372) were reported for ≤202 weeks. AE occurrences were low and consistent with previous analyses. The as-observed proportion of FIL200-treated patients in pMCS, biomarker and HRQoL remission during SELECTIONLTE remained high among completers (week 144: 80.0%, 86.4% and 86.0%, respectively) and increased among non-responders (week 192: 62.1%, 76.7% and 59.3%, respectively). Significantly higher proportions of CDC achievers at SELECTION week 58 achieved pMCS, IBDQ and corticosteroid-free pMCS remission than non-achievers, up to LTE week 96.
Filgotinib induced and maintained symptomatic remission and improved HRQoL over 4 years. Safety results showed a proven long-term benefit-risk profile. FIL200-treated CDC achievers had better long-term outcomes than non-achievers.
口服、每日一次、Janus 激酶 1 选择性抑制剂 Filgotinib 已获批用于治疗中重度活动性溃疡性结肠炎。
本研究旨在评估 2b/3 期 SELECTION 试验（SELECTIONLTE；NCT02914535）的长期扩展研究中继续使用 Filgotinib 治疗的安全性和疗效。
在 SELECTIONLTE 的中期分析中，SELECTION 完成者（第 10 周对 Filgotinib 有反应并完成维持研究的患者）继续接受其分配的治疗（双盲 Filgotinib 200mg[FIL200]或 Filgotinib 100mg），SELECTION 第 10 周无应答者接受开放标签 FIL200。我们通过不良事件（AE）评估安全性，并通过部分 Mayo 临床评分（pMCS）、炎症生物标志物和健康相关生活质量（HRQoL）评估疗效。我们比较了实现多成分终点（包括症状、内镜、炎症生物标志物和 HRQoL 改善）全面疾病控制（CDC）的达标者和非达标者的安全性和疗效。
对完成者（n=250）和无应答者（n=372）的数据进行了≤202 周的报告。AE 发生率较低，与之前的分析一致。在 SELECTIONLTE 期间，完成者的 pMCS、生物标志物和 HRQoL 缓解的 FIL200 治疗患者的比例观察到的比例仍然较高（第 144 周：80.0%、86.4%和 86.0%），并且无应答者的比例增加（第 192 周：62.1%、76.7%和 59.3%）。在第 58 周达到 CDC 的患者中，达到 pMCS、IBDQ 和无皮质类固醇的 pMCS 缓解的比例显著高于未达到的患者，直至 LTE 第 96 周。
Filgotinib 在 4 年内诱导并维持症状缓解并改善了 HRQoL。安全性结果显示了长期获益风险的有利特征。达到 CDC 的 FIL200 治疗患者的长期结局优于未达到的患者。
