Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Flanders, Belgium
Division of Rheumatology, University Hospitals KU Leuven, Leuven, Flanders, Belgium.
Ann Rheum Dis. 2021 Jun;80(6):727-738. doi: 10.1136/annrheumdis-2020-219213. Epub 2021 Jan 15.
To investigate efficacy and safety of the Janus kinase-1 inhibitor filgotinib in patients with active rheumatoid arthritis (RA) with limited or no prior methotrexate (MTX) exposure.
This 52-week, phase 3, multicentre, double-blind clinical trial (NCT02886728) evaluated once-daily oral filgotinib in 1252 patients with RA randomised 2:1:1:2 to filgotinib 200 mg with MTX (FIL200 +MTX), filgotinib 100 mg with MTX (FIL100 +MTX), filgotinib 200 mg monotherapy (FIL200), or MTX. The primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 24.
The primary endpoint was achieved by 81% of patients receiving FIL200+ MTX versus 71% receiving MTX (p<0.001). A significantly greater proportion treated with FIL100+ MTX compared with MTX achieved an ACR20 response (80%, p=0.017) at week 24. Significant improvement in Health Assessment Questionnaire-Disability Index was seen at week 24; least-squares mean change from baseline was -1.0 and -0.94 with FIL200+MTX and FIL100+MTX, respectively, versus -0.81 with MTX (p<0.001, p=0.008, respectively). Significantly higher proportions receiving FIL200+MTX (54%) and FIL100+MTX (43%) achieved DAS28(CRP) <2.6 versus MTX (29%) (p<0.001 for both) at week 24. Hierarchical testing stopped for comparison of ACR20 for FIL200 monotherapy (78%) versus MTX (71%) at week 24 (p=0.058). Adverse event rates through week 52 were comparable between all treatments.
FIL200+MTX and FIL100+MTX both significantly improved signs and symptoms and physical function in patients with active RA and limited or no prior MTX exposure; FIL200 monotherapy did not have a superior ACR20 response rate versus MTX. Filgotinib was well tolerated, with acceptable safety compared with MTX.
评估 Janus 激酶-1 抑制剂 filgotinib 对既往接受甲氨蝶呤（MTX）治疗有限或无 MTX 暴露的活动性类风湿关节炎（RA）患者的疗效和安全性。
这是一项为期 52 周、多中心、双盲的 3 期临床试验（NCT02886728），评估了每日口服 filgotinib 在 1252 例 RA 患者中的疗效，这些患者按 2:1:1:2 的比例随机接受 filgotinib 200mg+MTX（FIL200+MTX）、filgotinib 100mg+MTX（FIL100+MTX）、filgotinib 200mg 单药治疗（FIL200）或 MTX。主要终点为第 24 周时接受 filgotinib 200+MTX 治疗的患者达到美国风湿病学会（ACR）20%改善的比例。
接受 FIL200+MTX 治疗的患者中有 81%达到主要终点，而接受 MTX 治疗的患者中有 71%达到主要终点（p<0.001）。与 MTX 相比，接受 FIL100+MTX 治疗的患者在第 24 周时达到 ACR20 反应的比例显著更高（80%，p=0.017）。第 24 周时健康评估问卷残疾指数有显著改善；与 MTX 相比，FIL200+MTX 和 FIL100+MTX 治疗的患者基线时的最小二乘均数变化分别为-1.0 和-0.94（p<0.001，p=0.008）。第 24 周时，接受 FIL200+MTX（54%）和 FIL100+MTX（43%）治疗的患者达到 DAS28（CRP）<2.6的比例显著高于 MTX（29%）（均 p<0.001）。第 24 周时，与 MTX 相比，接受 FIL200 单药治疗的患者达到 ACR20 的比例更高（78%）（p=0.058）。
FIL200+MTX 和 FIL100+MTX 均显著改善了既往接受有限或无 MTX 治疗的活动性 RA 患者的体征和症状以及身体功能；与 MTX 相比，FIL200 单药治疗并未提高 ACR20 反应率。与 MTX 相比，filgotinib 具有良好的耐受性，安全性可接受。
