接受治疗中位数为 1.6 年的中重度活动性类风湿关节炎患者的 filgotinib 的综合安全性分析。
Integrated safety analysis of filgotinib in patients with moderately to severely active rheumatoid arthritis receiving treatment over a median of 1.6 years.
机构信息
Oregon Health & Science University, Portland, Oregon, USA
The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
出版信息
Ann Rheum Dis. 2022 Feb;81(2):184-192. doi: 10.1136/annrheumdis-2021-221051. Epub 2021 Nov 5.
OBJECTIVE
To characterise safety of the Janus kinase-1 preferential inhibitor filgotinib in patients with moderately to severely active rheumatoid arthritis.
METHODS
Data were integrated from seven trials (NCT01668641, NCT01894516, NCT02889796, NCT02873936, NCT02886728, NCT02065700, NCT03025308). Results are from placebo (PBO)-controlled (through week (W)12) and long-term, as-treated (all available data for patients receiving ≥1 dose filgotinib 200 (FIL200) or 100 mg (FIL100) daily) datasets. We calculated exposure-adjusted incidence rates (EAIRs)/100 patient-years filgotinib exposure (100PYE) for treatment-emergent adverse events (TEAEs).
RESULTS
3691 patients received filgotinib for 6080.7 PYE (median 1.6, maximum 5.6 years). During the PBO-controlled period, TEAEs, including those of grade ≥3, occurred at comparable rates with filgotinib or PBO; long-term EAIRs of TEAEs grade ≥3 were 6.4 and 7.6/100PYE for FIL200 and FIL100. EAIRs for deaths were 0.6/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 0.5 and 0.3/100PYE for FIL200 and FIL100. EAIRs for serious infection were 3.9, 3.3 and 2.4/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 1.6 and 3.1/100PYE for FIL200 and FIL100. EAIRs for herpes zoster were 0.6, 1.1, and 1.1/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 1.8 and 1.1/100PYE for FIL200 and FIL100. EAIRs for major adverse cardiovascular events were 0, 1.7 and 1.1/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 0.4 and 0.6/100PYE for FIL200 and FIL100. No venous thromboembolism occurred during the PBO-controlled period; long-term EAIRs were 0.2 and 0/100PYE for FIL200 and FIL100.
CONCLUSIONS
Over a median of 1.6 and maximum of 5.6 years of exposure, safety/tolerability of FIL200 and FIL100 were similar, with a lower incidence of infections with FIL200 among the long-term, as-treated dataset.
目的
描述中重度活跃性类风湿关节炎患者使用 Janus 激酶-1 选择性抑制剂 filgotinib 的安全性。
方法
数据来自 7 项试验（NCT01668641、NCT01894516、NCT02889796、NCT02873936、NCT02886728、NCT02065700、NCT03025308）。结果来自安慰剂（PBO）对照（至第 12 周）和长期（所有接受≥1 次 200 毫克（FIL200）或 100 毫克（FIL100）每日 filgotinib 治疗的患者的可用数据）数据集。我们计算了治疗期出现的不良事件（TEAEs）的暴露调整发生率（EAIR）/100 患者年 filgotinib 暴露量（100PYE）。
结果
3691 名患者接受 filgotinib 治疗，共 6080.7 PYE（中位数 1.6，最长 5.6 年）。在 PBO 对照期间，filgotinib 和 PBO 的 TEAEs 发生率相当，包括≥3 级 TEAEs；长期治疗组≥3 级 TEAEs 的 EAIR 分别为 FIL200 和 FIL100 组的 6.4 和 7.6/100PYE。FIL200 和 FIL100 的死亡率分别为 0.6/100PYE，PBO 组为 0.6/100PYE；长期 EAIR 分别为 FIL200 和 FIL100 组的 0.5 和 0.3/100PYE。严重感染的 EAIR 分别为 FIL200、FIL100 和 PBO 组的 3.9、3.3 和 2.4/100PYE；长期 EAIR 分别为 FIL200 和 FIL100 组的 1.6 和 3.1/100PYE。带状疱疹的 EAIR 分别为 FIL200、FIL100 和 PBO 组的 0.6、1.1 和 1.1/100PYE；长期 EAIR 分别为 FIL200 和 FIL100 组的 1.8 和 1.1/100PYE。主要不良心血管事件的 EAIR 分别为 FIL200、FIL100 和 PBO 组的 0、1.7 和 1.1/100PYE；长期 EAIR 分别为 FIL200 和 FIL100 组的 0.4 和 0.6/100PYE。在 PBO 对照期间未发生静脉血栓栓塞事件；长期 EAIR 分别为 FIL200 和 FIL100 组的 0.2 和 0/100PYE。
结论
在 1.6 年至最长 5.6 年的中位暴露时间内，FIL200 和 FIL100 的安全性/耐受性相似，长期治疗组中 FIL200 组的感染发生率较低。
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