Department of Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany.
Alimentiv, Inc., London, Ontario, Canada.
United European Gastroenterol J. 2024 Nov;12(9):1243-1255. doi: 10.1002/ueg2.12686. Epub 2024 Oct 25.
Filgotinib is an oral, once-daily, Janus kinase 1 preferential inhibitor approved for treatment of ulcerative colitis (UC) following the phase 2b/3 SELECTION trial. Identification of patient populations and factors associated with long-term treatment response trajectories may improve UC management.
We aimed to identify and describe distinct patient subgroups of response to filgotinib based on partial Mayo Clinic Score (pMCS) trajectories over time.
In these post hoc analyses of SELECTION, group-based trajectory modeling (GBTM) was applied to pMCS to describe groups of distinct, symptom-based patient trajectories using data from patients who responded to filgotinib 200 or 100 mg and continued receiving filgotinib up to week 58. Patient demographics, disease characteristics, and week 10 response were compared between the groups. Achievement of a patient-level multi-component endpoint of comprehensive disease control (CDC) was assessed in each group.
GBTM identified five distinct patient populations with different response trajectories; 67.5% of patients had beneficial trajectories. The beneficial trajectory groups generally had higher proportions of patients who were recently diagnosed (<1 year), were receiving filgotinib 200 mg and were biologic-naive versus the relapsing trajectory groups (4%-9% vs. 4%-5%; 43%-65% vs. 36%-46%; 54%-70% vs. 35%-58%, respectively). Furthermore, 55.4% of patients had sustained beneficial trajectories, with low baseline endoscopic subscores (≥43% of patients had a subscore of 2) and strong week 10 FCP responses (≥61% of patients with >50% decrease in FCP from baseline). Sustained beneficial trajectory groups had a higher probability of achieving CDC at week 58 than other groups (31%-32% vs. 0%-7%).
Beneficial long-term response trajectories and achievement of CDC with filgotinib were associated with being biologic-naive and having less severe disease at baseline. Early estimation of sustained and CDC may facilitate patient identification and development of personalized management strategies in UC.
NCT02914522.
Filgotinib 是一种每日口服一次的 Janus 激酶 1 选择性抑制剂，已在 2b/3 期 SELECTION 试验后获得溃疡性结肠炎（UC）的治疗批准。确定与长期治疗反应轨迹相关的患者人群和因素可能会改善 UC 的管理。
我们旨在根据时间推移时的部分 Mayo 诊所评分（pMCS）轨迹来确定并描述对 filgotinib 有不同反应的患者亚群。
在这些 SELECTION 的事后分析中，基于组的轨迹建模（GBTM）被应用于 pMCS，以使用对 filgotinib 200 或 100mg 有反应并持续接受 filgotinib治疗至第 58 周的患者的数据来描述基于症状的不同患者轨迹组。比较了组间患者的人口统计学特征、疾病特征和第 10 周的反应。评估了每个组中综合疾病控制（CDC）的患者水平多成分终点的实现。
GBTM 确定了五个具有不同反应轨迹的不同患者群体；67.5%的患者有获益轨迹。获益轨迹组通常具有更高比例的近期诊断（<1 年）、接受 filgotinib 200mg 和生物初治患者，而复发轨迹组则较低（4%-9%比 4%-5%；43%-65%比 36%-46%；54%-70%比 35%-58%）。此外，55.4%的患者具有持续获益的轨迹，基线内镜亚评分较低（≥43%的患者亚评分 2），第 10 周 FCP 反应较强（≥61%的患者 FCP 较基线下降>50%）。与其他组相比，持续获益轨迹组在第 58 周实现 CDC 的可能性更高（31%-32%比 0%-7%）。
与基线时疾病较轻且为生物初治患者相比，长期获益反应轨迹和达到 CDC 与使用 filgotinib 有关。早期估计持续和 CDC 可能有助于识别患者并制定 UC 的个性化管理策略。
NCT02914522。
