Aichi Development Disability Center, Kasugai, Japan.
The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Mod Rheumatol. 2023 Jan 3;33(1):64-72. doi: 10.1093/mr/roac020.
Characterize safety of the Janus kinase-1 preferential inhibitor filgotinib (FIL) in Japanese patients with moderately to severely active rheumatoid arthritis (RA).
Data from three Phase 3 trials (NCT02889796, NCT02873936, and NCT02886728) and a long-term extension (NCT03025308) through September 2019 were integrated; patients received ≥1 dose of FIL 200 (FIL200) or 100 mg (FIL100) daily, or placebo (PBO). We calculated exposure-adjusted incidence rates (EAIRs) per 100 patient-years FIL exposure (100PYE) for treatment-emergent adverse events (TEAEs) and adverse events of special interest.
Among 3691 total patients and 6080.7 PYE, 229 Japanese patients received FIL for 311.4 PYE (median 1.5, maximum 2.5 years). During the 12-week PBO-controlled period, serious TEAEs and TEAEs leading to study drug disruption were comparable between FIL and PBO. Serious infection rates were 1.9%, 0%, and 2% for FIL200, FIL100, and PBO during the PBO-controlled period; long-term FIL200 and FIL100 EAIRs were 3.8 and 2.1/100PYE. No herpes zoster (HZ) or major adverse cardiovascular events (MACEs) occurred during the PBO-controlled period; long-term FIL200 and FIL100 EAIRs were 3.0 and 2.1/100PYE (HZ) and 0.6 and 0/100PYE (MACE).
Long-term FIL treatment (median 1.5, maximum 2.5 years exposure) was well tolerated at 100- and 200-mg doses in Japanese patients with RA.
描述 Janus 激酶-1 选择性抑制剂 filgotinib（FIL）在日本中重度活跃型类风湿关节炎（RA）患者中的安全性。
整合了三项 3 期临床试验（NCT02889796、NCT02873936 和 NCT02886728）和一项长期扩展（NCT03025308）的数据；患者接受了 ≥1 剂 FIL200（FIL200）或 100mg（FIL100）每日，或安慰剂（PBO）。我们计算了暴露调整的治疗中出现的不良事件（TEAE）和特殊关注的不良事件的发生率（EAIR），每 100 患者年 FIL 暴露（100PYE）。
在 3691 名总患者和 6080.7 PYE 中，229 名日本患者接受 FIL 治疗 311.4 PYE（中位数 1.5，最大 2.5 年）。在 12 周的 PBO 对照期，FIL 和 PBO 的严重 TEAE 和导致研究药物中断的 TEAE 发生率相当。在 PBO 对照期，FIL200、FIL100 和 PBO 的严重感染率分别为 1.9%、0%和 2%；长期 FIL200 和 FIL100 的 EAIR 分别为 3.8 和 2.1/100PYE。在 PBO 对照期未发生带状疱疹（HZ）或主要不良心血管事件（MACE）；长期 FIL200 和 FIL100 的 EAIR 分别为 3.0 和 2.1/100PYE（HZ）和 0.6 和 0/100PYE（MACE）。
在日本 RA 患者中，100 和 200mg 剂量的长期 FIL 治疗（中位暴露时间 1.5 年，最长暴露时间 2.5 年）耐受性良好。
