Department of Dermatology, Yale School of Medicine, New Haven, Connecticut.
Department of Dermatology, Stanford University School of Medicine, Palo Alto, California.
JAMA Dermatol. 2024 Oct 1;160(10):1075-1081. doi: 10.1001/jamadermatol.2024.2734.
Baricitinib has demonstrated efficacy for treating severe alopecia areata in adults. There is currently limited information about the need for continuous therapy after achieving scalp hair regrowth.
To report results from the randomized withdrawal period of the BRAVE-AA1 trial.
DESIGN, SETTING, AND PARTICIPANTS: BRAVE-AA1 was a randomized, placebo-controlled, phase 3 randomized clinical trial with a treatment withdrawal substudy that was conducted at 70 centers in 3 countries beginning in March 2019. It included 654 adults with severe alopecia areata (AA) (Severity of Alopecia Tool [SALT] score ≥50) who were randomized 3:2:2 to receive treatment with baricitinib, 4 mg; baricitinib, 2 mg; or placebo. Data were analyzed in August 2023.
At week 52, 154 patients who were responders (SALT score ≤20) were rerandomized 3:1 to continue to take their current dose of baricitinib or transition to placebo (randomized withdrawal). Responders randomized to placebo who experienced a loss of treatment benefit (>20-point worsening in SALT score) at any time after week 52 were retreated with their original baricitinib dose.
The proportion of patients who lost treatment benefit through week 152 and the proportion of patients who recaptured response after retreatment. The last observation carried forward was used to impute missing or censored data.
Of 654 patients who received treatment, the mean (SD) age was 37.1 (13.0) years, and there were 383 women (58.6%). At week 52, 10 of 39 responders taking baricitinib, 2 mg, and 30 of 115 responders taking baricitinib, 4 mg, were rerandomized to placebo. At 4 and 8 weeks of treatment withdrawal, 0% and 10% to 11% of patients, respectively, lost treatment benefit regardless of dose. At week 152, 80% of patients had lost benefit compared with 7% for those who continued baricitinib therapy for both dose groups. Within the follow-up observation periods, 5 of 8 patients taking 2 mg (63%) and 21 of 24 patients taking 4 mg (87.5%) recaptured a SALT score of 20 or less response after retreatment.
Severe AA is a chronic, relapsing condition, and this randomized clinical trial found that withdrawal of therapy for a patient population with severe AA who had achieved meaningful hair regrowth after 1 year of treatment with baricitinib resulted in loss of benefit for almost all patients, indicating that continued therapy is required to maintain hair regrowth.
ClinicalTrials.gov Identifier: NCT03570749.
巴瑞替尼已被证明对成人严重斑秃有效。目前，关于在获得头皮毛发再生后是否需要持续治疗的信息有限。
报告 BRAVE-AA1 试验随机停药期的结果。
设计、地点和参与者：BRAVE-AA1 是一项随机、安慰剂对照、为期 3 期的临床试验，设有治疗停药亚研究，于 2019 年 3 月在 3 个国家的 70 个中心开始进行。纳入 654 名患有严重斑秃（AA）（脱发严重程度工具[SALT]评分≥50）的成年人，随机分为 3:2:2 接受巴瑞替尼 4mg、巴瑞替尼 2mg 或安慰剂治疗。数据于 2023 年 8 月进行分析。
在第 52 周，154 名应答者（SALT 评分≤20）被重新随机分为 3:1 继续接受当前剂量的巴瑞替尼或转为安慰剂（随机停药）。在第 52 周后任何时间出现治疗获益丧失（SALT 评分恶化≥20 分）的随机接受安慰剂的应答者，用原始巴瑞替尼剂量进行重新治疗。
截至第 152 周时治疗获益丧失的患者比例，以及重新治疗后应答恢复的患者比例。最后一次观察结转用于推断缺失或删失数据。
在接受治疗的 654 名患者中，平均（SD）年龄为 37.1（13.0）岁，其中 383 名为女性（58.6%）。在第 52 周，39 名接受巴瑞替尼 2mg 治疗的应答者中有 10 名和 115 名接受巴瑞替尼 4mg 治疗的应答者中有 30 名被重新随机分配至安慰剂。在停药 4 周和 8 周时，无论剂量如何，分别有 0%至 11%的患者失去了治疗获益。在第 152 周时，与继续接受两种剂量巴瑞替尼治疗的患者相比，80%的患者失去了获益，而只有 7%的患者获益。在随访观察期间，8 名接受 2mg 治疗的患者中有 5 名（63%）和 24 名接受 4mg 治疗的患者中有 21 名（87.5%）重新获得了 SALT 评分 20 或更低的应答。
严重 AA 是一种慢性、复发性疾病，这项随机临床试验发现，在接受巴瑞替尼治疗 1 年后，严重 AA 患者的毛发显著再生，停药后几乎所有患者都失去了获益，这表明需要继续治疗以维持毛发再生。
ClinicalTrials.gov 标识符：NCT03570749。
