Westhovens Rene, Winthrop Kevin L, Kavanaugh Arthur, Greenwald Maria, Dagna Lorenzo, Cseuz Regina, Besuyen Robin, de Vries Dick, Modgill Vikas, Le Ly Huong, Genovese Mark C, Emery Paul, Verschueren Patrick, Alten Rieke
Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium
School of Medicine, Oregon Health and Science University, Portland, Oregon, USA.
RMD Open. 2025 Jan 30;11(1):e004857. doi: 10.1136/rmdopen-2024-004857.
DARWIN 3 (ClinicalTrials.gov: NCT02065700) assessed the safety and efficacy of filgotinib in a long-term extension (LTE) of two phase II randomised controlled rheumatoid arthritis (RA) trials.
Eligible patients completing the 24-week DARWIN 1 (filgotinib plus methotrexate) and DARWIN 2 (filgotinib monotherapy) trials could enrol. Patients received filgotinib 200 mg/day, except 15 men who received filgotinib 100 mg/day. The primary endpoints were safety and tolerability, which were assessed by the incidence of treatment-emergent adverse events (TEAEs). Safety and efficacy analyses included all enrolled patients who received ≥1 dose of filgotinib in DARWIN 3.
739 patients entered the LTE. The total patient-years of exposure (PYE) to filgotinib was 3706.3 years; the mean exposure duration was 259.8 weeks. 497 patients (67.3%) discontinued prematurely (including 266 TEAEs and 172 withdrawals due to the patient's decision or 'sponsor request'). Overall exposure-adjusted incidence rate (EAIR) was 67 (95% CI 62 to 72.2)/100 PYE for TEAEs and 3.8 (95% CI 3.2 to 4.5)/100 PYE for serious TEAEs. EAIR of infections was 23.3 (95% CI 21.2 to 25.6)/100 PYE, 1.3 (95% CI 0.9 to 1.7)/100 PYE for serious infections and 1.3 (95% CI 0.9 to 1.7)/100 PYE for herpes zoster. EAIRs of major adverse cardiovascular events (0.19 (95% CI 0.8 to 0.39)/100 PYE) and malignancies (0.6 (95% CI 0.4 to 0.9)/100 PYE) were low. Disease response assessed using non-responder imputation plateaued at LTE week 12 before slowly declining over time, with overall American College of Rheumatology (ACR)20/50/70 response rates of 26.9%/20.2%/14.7% at week 396.
Filgotinib was well tolerated in patients with RA for up to 8 years. Safety and efficacy profiles were maintained in patients previously receiving either filgotinib plus methotrexate or filgotinib monotherapy.
DARWIN 3（ClinicalTrials.gov：NCT02065700）在两项II期类风湿性关节炎（RA）随机对照试验的长期扩展研究（LTE）中评估了非戈替尼的安全性和有效性。
完成24周DARWIN 1（非戈替尼加甲氨蝶呤）和DARWIN 2（非戈替尼单药治疗）试验的符合条件的患者可以入组。患者接受200毫克/天的非戈替尼治疗，但有15名男性患者接受100毫克/天的非戈替尼治疗。主要终点是安全性和耐受性，通过治疗中出现的不良事件（TEAE）的发生率进行评估。安全性和有效性分析包括在DARWIN 3中接受≥1剂非戈替尼治疗的所有入组患者。
739名患者进入长期扩展研究。非戈替尼的总患者暴露年数（PYE）为3706.3年；平均暴露持续时间为259.8周。497名患者（67.3%）提前停药（包括266例TEAE和172例因患者决定或“申办方要求”而退出）。TEAE的总体暴露调整发病率（EAIR）为67（95%CI 62至72.2）/100 PYE，严重TEAE的EAIR为3.8（95%CI 3.2至4.5）/100 PYE。感染的EAIR为23.3（95%CI 21.2至25.6）/100 PYE，严重感染为1.3（95%CI 0.9至1.7）/100 PYE，带状疱疹为1.3（95%CI 0.9至1.7）/100 PYE。主要不良心血管事件（0.19（95%CI 0.08至0.39）/100 PYE）和恶性肿瘤（0.6（95%CI 0.4至0.9）/100 PYE）的EAIR较低。使用无反应者插补法评估的疾病反应在长期扩展研究第12周达到平稳，随后随时间缓慢下降，在第396周时美国风湿病学会（ACR）20/50/70的总体反应率分别为26.9%/20.2%/14.7%。
非戈替尼在RA患者中耐受性良好，长达8年。先前接受非戈替尼加甲氨蝶呤或非戈替尼单药治疗的患者的安全性和有效性特征得以维持。
