Yale School of Medicine, New Haven, CT, USA.
New York University Langone Health, New York City, NY, USA.
Br J Dermatol. 2023 Nov 16;189(6):666-673. doi: 10.1093/bjd/ljad253.
Baricitinib is approved for the treatment of adults with severe alopecia areata (AA). In the absence of robust data on the patterns of regrowth during treatment of severe AA, there is a gap in the knowledge regarding treatment expectations.
To examine whether different clinical response subgroups could be identified in baricitinib-treated patients with severe AA and factors that contribute to these subgroups.
The BRAVE-AA1 and BRAVE-AA2 phase III trials enrolled patients with severe AA [Severity of Alopecia Tool (SALT) score ≥ 50 (≥ 50% scalp hair loss)]. Patients randomized to baricitinib 4 mg or 2 mg retained their treatment allocation for 52 weeks. Based on patterns identified through growth mixture modelling (GMM), patients were categorized into responder subgroups according to when they first achieved ≥ 30% improvement from baseline in SALT score (SALT30). For each responder subgroup, trajectories of response (i.e. achievement of a SALT score ≤ 20, SALT score ≤ 10 and ≥ 50% change from baseline in SALT score) and baseline disease characteristics are reported.
Respectively, 515 and 340 patients were randomized to once-daily baricitinib 4 mg and 2 mg at baseline; 69% and 51%, respectively, achieved SALT30 at least once by week 52. Based on GMM findings, we identified three responder subgroups: early (SALT30 by week 12), gradual (SALT30 after week 12-week 36) and late (SALT30 after week 36-week 52). The proportions of early, gradual and late responders and nonresponders were, respectively, 33%, 28%, 8% and 31% among patients treated with baricitinib 4 mg, and 20%, 23%, 9% and 49%, respectively, among those treated with baricitinib 2 mg. Early responders had a shorter trajectory to maximal clinical outcomes (e.g. > 78% achieved a SALT score ≤ 20 by week 36) vs. gradual or late responders. Early responders were more frequent among patients with baseline severe AA (SALT score 50 to < 95) vs. very severe AA (SALT score 95-100). Overall, responders (early to late) were more frequent in patients with short (< 4 years) episodes of hair loss.
These analyses identified early, gradual and late responder subgroups for scalp hair regrowth in baricitinib-treated patients with severe AA, and that these subgroups are influenced by baseline characteristics. Findings from these analyses will help to inform treatment expectations for scalp hair regrowth.
巴瑞替尼已获批用于治疗成人严重斑秃（AA）。由于缺乏关于严重 AA 治疗期间再生模式的可靠数据，因此在治疗预期方面存在知识空白。
探讨巴瑞替尼治疗严重 AA 患者中是否可以识别不同的临床应答亚组，以及哪些因素导致这些亚组的出现。
BRAVE-AA1 和 BRAVE-AA2 三期临床试验纳入了严重 AA 患者[脱发严重程度评估工具（SALT）评分≥50（≥50%头皮毛发缺失）]。随机分配至巴瑞替尼 4mg 或 2mg 组的患者在 52 周内维持其治疗分组。基于通过生长混合建模（GMM）确定的模式，根据他们首次达到 SALT 评分≥30%改善时的时间（SALT30），将患者分类为应答亚组。对于每个应答亚组，报告应答轨迹（即达到 SALT 评分≤20、SALT 评分≤10 和 SALT 评分较基线变化≥50%）和基线疾病特征。
分别有 515 名和 340 名患者在基线时随机分配至每日一次巴瑞替尼 4mg 和 2mg，分别有 69%和 51%的患者在第 52 周时至少达到过一次 SALT30。基于 GMM 结果，我们确定了三个应答亚组：早期（第 12 周达到 SALT30）、渐进（第 12 周至第 36 周达到 SALT30）和晚期（第 36 周至第 52 周达到 SALT30）。巴瑞替尼 4mg 治疗组中，早期、渐进和晚期应答者和无应答者的比例分别为 33%、28%、8%和 31%，巴瑞替尼 2mg 治疗组中分别为 20%、23%、9%和 49%。与渐进或晚期应答者相比，早期应答者达到最大临床结局（例如，第 36 周时＞78%的患者达到 SALT 评分≤20）的轨迹更短。早期应答者更常见于基线严重 AA（SALT 评分 50 至＜95）患者，而非非常严重 AA（SALT 评分 95-100）患者。总体而言，早期、渐进和晚期应答者（统称应答者）更常见于脱发发作时间较短（＜4 年）的患者。
这些分析确定了巴瑞替尼治疗严重 AA 患者头皮毛发再生的早期、渐进和晚期应答亚组，这些亚组受基线特征的影响。这些分析结果将有助于为头皮毛发再生提供治疗预期。
