Department of Dermatology, Stanford University School of Medicine, Stanford, California.
Department of Dermatology, Heersink School of Medicine, University of Alabama at Birmingham.
JAMA Dermatol. 2023 Sep 1;159(9):970-976. doi: 10.1001/jamadermatol.2023.2581.
Baricitinib is an oral selective Janus kinase 1/2 inhibitor that has achieved clinically meaningful outcomes for scalp, eyebrow, and eyelash hair regrowth in patients with severe alopecia areata (AA) at week 36 of treatment. Treatment with baricitinib, 4 mg, has resulted in higher response rates than baricitinib, 2 mg, at weeks 36 and 52.
To determine the efficacy of uptitration to baricitinib, 4 mg, for 24 weeks in patients who had previously not responded to baricitinib, 2 mg (Severity of Alopecia Tool [SALT] score of >20).
DESIGN, SETTING, AND PARTICIPANTS: BRAVE-AA1 and BRAVE-AA2 are multicenter, placebo-controlled, phase 3 randomized clinical trials that were initiated on September 24, 2018, and July 8, 2019, respectively, with follow-up to 200 weeks (data cutoffs of November 11, 2021, and November 5, 2021, respectively). This pooled analysis reports long-term extension data up to week 76. At baseline, 1200 adult patients with severe AA (SALT score ≥50) were randomly assigned in a 3:2:2 ratio to receive baricitinib, 4 mg; baricitinib, 2 mg; or placebo. Patients treated with baricitinib remained on the same treatment dose until week 52. Patients were considered nonresponders to baricitinib, 2 mg, if they had a SALT score greater than 20 after 52 weeks of therapy.
The proportions of patients achieving a SALT score of 20 or lower and clinician-reported outcome for eyebrow hair loss and eyelash hair loss scores of 0 or 1 (full coverage or minimal gaps) with 2-point or higher improvements from baseline (among those with baseline scores ≥2 [significant gaps to no notable hair]) were analyzed through week 76.
At week 52, of the 340 patients (mean [SD] age, 38.4 [12.9] years; 212 [62.4%] female) treated with baricitinib, 2 mg, 212 (62.4%) had a SALT score higher than 20 and were uptitrated to baricitinib, 4 mg. Two-thirds of these patients (142 of 212 [67.0%]) had a baseline SALT score of 95 to 100, indicating very severe AA. At week 76, 55 of the 212 patients (25.9%) had achieved a SALT score of 20 or lower. During the same period, response rates for clinician-reported outcome scores of 0 or 1 increased from 19.3% (31 of 161 patients) to 37.9% (61 of 161 patients) for eyebrows and from 24.1% (33 of 137 patients) to 40.9% (56 of 137 patients) for eyelashes.
In this pooled analysis of the BRAVE-AA1 and BRAVE-AA2 trials, uptitration of baricitinib, 2 mg, to baricitinib, 4 mg, in those who did not respond to the 2-mg dose resulted in meaningful improvement of response rates over the subsequent 24 weeks for scalp, eyebrow, and eyelash hair loss.
ClinicalTrials.gov Identifiers: NCT03570749 and NCT03899259.
重要性：巴瑞替尼是一种口服选择性 Janus 激酶 1/2 抑制剂，在第 36 周治疗时，已在患有严重斑秃（AA）的患者中实现了头皮、眉毛和睫毛再生的有临床意义的结果。与巴瑞替尼 2 毫克相比，巴瑞替尼 4 毫克治疗导致更高的反应率，在第 36 周和第 52 周时达到更高的反应率。
目的：确定先前对巴瑞替尼 2 毫克（SALT 评分>20）无反应的患者上调至巴瑞替尼 4 毫克的疗效，治疗 24 周。
设计、地点和参与者：BRAVE-AA1 和 BRAVE-AA2 是两项多中心、安慰剂对照、3 期随机临床试验，分别于 2018 年 9 月 24 日和 2019 年 7 月 8 日启动，随访至 200 周（数据截止日期分别为 2021 年 11 月 11 日和 2021 年 11 月 5 日）。这项汇总分析报告了长达 76 周的长期扩展数据。在基线时，1200 名患有严重 AA（SALT 评分≥50）的成年患者按 3:2:2 的比例随机分配接受巴瑞替尼 4 毫克；巴瑞替尼 2 毫克；或安慰剂。接受巴瑞替尼治疗的患者在第 52 周前继续接受相同剂量的治疗。如果患者在 52 周治疗后 SALT 评分大于 20，则被认为对巴瑞替尼 2 毫克无反应。
主要结果和措施：通过分析至第 76 周的 SALT 评分 20 或更低的患者比例和临床医生报告的眉毛和睫毛脱发评分 0 或 1（完全覆盖或最小间隙），以及与基线相比 2 点或更高的改善（基线评分≥2 [显著间隙到无明显毛发]）。
结果：在第 52 周，340 名（平均[标准差]年龄，38.4[12.9]岁；212 [62.4%]为女性）接受巴瑞替尼 2 毫克治疗的患者中，212 名（62.4%）SALT 评分大于 20，上调至巴瑞替尼 4 毫克。这些患者中有三分之二（142 名[67.0%]）基线 SALT 评分为 95 至 100，表明患有非常严重的 AA。在第 76 周，212 名患者中有 55 名（25.9%）SALT 评分达到 20 或更低。在此期间，临床医生报告的 0 或 1 分的反应率从 19.3%（161 名患者中的 31 名）增加到 37.9%（161 名患者中的 61 名），眉毛的反应率从 24.1%（137 名患者中的 33 名）增加到 40.9%（137 名患者中的 56 名）。
结论和相关性：在 BRAVE-AA1 和 BRAVE-AA2 试验的这项汇总分析中，对 2 毫克剂量无反应的患者上调至巴瑞替尼 4 毫克，在随后的 24 周内，头皮、眉毛和睫毛脱发的反应率显著提高。
试验注册：ClinicalTrials.gov 标识符：NCT03570749 和 NCT03899259。
