King Brett, Guttman-Yassky Emma, Peeva Elena, Banerjee Anindita, Zhu Linda, Zhu Hua, Cox Lori Ann, Vincent Michael S, Sinclair Rodney
Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA.
Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
JID Innov. 2022 Sep 7;2(6):100156. doi: 10.1016/j.xjidi.2022.100156. eCollection 2022 Nov.
The 24-week, double-blind period of the ALLEGRO phase 2a trial (NCT02974868) evaluated the safety and efficacy of ritlecitinib (Jak3/tyrosine kinase expressed in the hepatocellular carcinoma inhibitor) and brepocitinib (tyrosine kinase 2/Jak1 inhibitor) in patients with alopecia areata; patients could subsequently continue treatment in a 24-week single-blind extension, followed by a crossover open-label extension, described in this article. Patients who did not achieve ≥30% improvement from baseline in Severity of Alopecia Tool score at the end of the single-blind extension entered a 24-week crossover open-label extension: the ritlecitinib group switched to brepocitinib, and the brepocitinib group switched to ritlecitinib. Eighteen patients switched to brepocitinib, and five switched to ritlecitinib. Six treatment-emergent adverse events were reported by five patients; no new safety risks were observed after crossover. An exploratory efficacy evaluation showed that none of the five patients receiving ritlecitinib in the crossover open-label extension achieved ≥30% improvement from baseline in Severity of Alopecia Tool score or improvement in eyebrow/eyelash assessments. Four of 16 patients receiving brepocitinib achieved ≥30% improvement from baseline in Severity of Alopecia Tool score or better; 4 of 15 and 5 of 12 showed improvement in eyebrow and eyelash assessments, respectively. Although the small number of patients precludes firm conclusions regarding efficacy, the data suggest that some patients with alopecia areata and inadequate response to ritlecitinib after ≥24 weeks show benefit after switching to brepocitinib.
ALLEGRO 2a期试验（NCT02974868）的24周双盲阶段评估了芦可替尼（肝细胞癌抑制剂中表达的Jak3/酪氨酸激酶）和布雷西替尼（酪氨酸激酶2/Jak1抑制剂）在斑秃患者中的安全性和有效性；患者随后可在24周单盲延长期继续治疗，然后进入本文所述的交叉开放标签延长期。在单盲延长期结束时，脱发严重程度工具评分未从基线改善≥30%的患者进入24周交叉开放标签延长期：芦可替尼组改用布雷西替尼，布雷西替尼组改用芦可替尼。18名患者改用布雷西替尼，5名患者改用芦可替尼。5名患者报告了6例治疗中出现的不良事件；交叉后未观察到新的安全风险。一项探索性疗效评估显示，在交叉开放标签延长期接受芦可替尼治疗的5名患者中，没有一人在脱发严重程度工具评分或眉毛/睫毛评估方面从基线改善≥30%。接受布雷西替尼治疗的16名患者中有4名在脱发严重程度工具评分方面从基线改善≥30%或更好；15名患者中有4名、12名患者中有5名在眉毛和睫毛评估方面有所改善。尽管患者数量较少，无法就疗效得出确凿结论，但数据表明，一些斑秃患者在≥24周后对芦可替尼反应不足，改用布雷西替尼后显示出获益。
