在两项III期试验中，巴瑞替尼治疗重度斑秃成人患者长达4年（中位治疗时间2.3年）的安全性。
Safety of Baricitinib in Adults with Severe Alopecia Areata from Two Phase III Trials Over a Median of 2.3 Years and Up to 4 Years of Treatment.
作者信息
King Brett, Mostaghimi Arash, Shimomura Yutaka, Piraccini Bianca Maria, Blume-Peytavi Ulrike, Sontag Angelina, Dutronc Yves, Denning Karen, Kolodsick Jill, Lu Xiaoyu, Srivastava Ayush, Sinclair Rodney
机构信息
Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
Dermatology Physicians of Connecticut-Fairfield, 425 Post Road, 2nd Floor, Fairfield, CT, 06824, USA.
出版信息
Am J Clin Dermatol. 2025 Apr 11. doi: 10.1007/s40257-025-00932-0.
BACKGROUND
We report pooled safety data for baricitinib treatment of severe alopecia areata in patients in BRAVE-AA1 (phase II/III) and BRAVE-AA2 (phase III), including data from the long-term extension and bridging extension periods.
METHODS
Data are reported from the extended dataset (patients receiving continuous baricitinib 2 mg or 4 mg) and the all-baricitinib dataset (all patients receiving any dose of baricitinib at any time during the trials). Safety outcomes include treatment-emergent adverse events, adverse events of special interest, and abnormal changes in laboratory test results. Incidence rates (IRs) per 100 patient-years were calculated based on time at risk. Data cutoff dates were 22 May, 2023, for BRAVE-AA1 and 8 May, 2023, for BRAVE-AA2 and included follow-up through at least 152 weeks.
RESULTS
Data were collected for 1303 patients treated with baricitinib, reflecting 2789.7 patient-years of exposure (median, 825 days; maximum, 1460 days). Most treatment-emergent adverse events were mild to moderate in severity. Incidence rates of serious adverse events (IR = 2.6) and treatment discontinuations because of adverse events (IR = 1.7) were generally low and remained similar to data presented through at least 104 weeks of follow-up. In an additional 1 year of follow-up, no new cases of serious infections, opportunistic infections, major adverse cardiovascular events, deep vein thromboses, or pulmonary embolisms were observed. The IRs for non-melanoma skin cancer (IR = 0.1) and other malignancies (IR = 0.2) remained stable over time. The IR of herpes zoster was comparable to previously reported IRs (IR = 1.9). Laboratory changes were generally consistent over time. No deaths were reported in either study.
CONCLUSIONS
Long-term safety data from BRAVE-AA1 and BRAVE-AA2 are consistent with previously reported data from the baricitinib alopecia areata clinical trial program and demonstrate no new safety concerns or signals for baricitinib through a maximum exposure of 4 years.
CLINICAL TRIAL REGISTRATION
BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259) were registered on 18 June, 2018, and 1 April, 2019, respectively.
背景
我们报告了在BRAVE - AA1（II/III期）和BRAVE - AA2（III期）试验中使用巴瑞替尼治疗重度斑秃患者的汇总安全性数据，包括长期扩展期和桥接扩展期的数据。
方法
数据来自扩展数据集（接受2 mg或4 mg巴瑞替尼持续治疗的患者）和全巴瑞替尼数据集（在试验期间任何时间接受任何剂量巴瑞替尼的所有患者）。安全性结局包括治疗中出现的不良事件、特别关注的不良事件以及实验室检查结果的异常变化。每100患者年的发生率基于风险时间计算。BRAVE - AA1的数据截止日期为2023年5月22日，BRAVE - AA2的数据截止日期为2023年5月8日，随访时间至少为152周。
结果
共收集了1303例接受巴瑞替尼治疗患者的数据，反映了2789.7患者年的暴露时间（中位数为825天；最长为1460天）。大多数治疗中出现的不良事件严重程度为轻度至中度。严重不良事件的发生率（IR = 2.6）和因不良事件导致的治疗中断率（IR = 1.7）总体较低，并且与至少104周随访期内公布的数据相似。在额外1年的随访中，未观察到严重感染、机会性感染、主要不良心血管事件、深静脉血栓形成或肺栓塞的新病例。非黑色素瘤皮肤癌的发生率（IR = 0.1）和其他恶性肿瘤的发生率（IR = 0.2）随时间保持稳定。带状疱疹的发生率与先前报告的发生率相当（IR = 1.9）。实验室检查结果随时间总体保持一致。两项研究均未报告死亡病例。
结论
BRAVE - AA1和BRAVE - AA2的长期安全性数据与巴瑞替尼斑秃临床试验项目先前报告的数据一致，并且在最长4年的暴露期内未显示出巴瑞替尼有新的安全问题或信号。
临床试验注册
BRAVE - AA1（NCT03570749）和BRAVE - AA2（NCT03899259）分别于2018年6月18日和2019年4月1日注册。
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