美国耶鲁医学院Brett King团队研究了巴瑞替尼治疗斑秃的临床3期效果。相关论文于2022年3月26日发表在《新英格兰医学杂志》上。

斑秃是一种自身免疫性疾病，其特征是头皮、眉毛和睫毛迅速脱发，治疗方法有限。巴瑞替尼是一种口服、选择性、可逆的Janus激酶1和2抑制剂，可阻断与斑秃发病机制有关的细胞因子信号。

研究组进行了两项随机、安慰剂对照的3期临床试验（BRAVE-AA1和BRAVE-AA2），招募严重斑秃的成年人，其脱发严重程度工具（SALT）评分为50分或更高（范围为0[无头皮脱发]至100[完全头皮脱发]）。将患者按3:2:2的比例随机分配，每天服用一次剂量为4 mg的巴瑞替尼、2 mg的巴瑞替尼或安慰剂治疗。主要结局是在第36周时，SALT评分为20分及以下。

研究组在BRAVE-AA1试验中共招募了654名患者，在BRAVE-AA2试验中共招募了546名患者。第36周时，4 mg巴瑞替尼、2 mg巴瑞替尼和安慰剂的BRAVE-AA1患者中SALT不超过20分的估计百分比分别为38.8%、22.8%和6.2%，相应的BRAVE-AA2患者中分别为35.9%、19.4%和3.3%。

在BRAVE-AA1组中，4 mg巴瑞替尼和安慰剂之间的差异为32.6个百分点，2 mg巴瑞替尼和安慰剂之间的差异为16.6个百分点，均具有统计学意义。在BRAVE-AA2组中，相应的数值分别为32.6个百分点和16.1个百分点，差异亦显著。

与安慰剂组相比，4 mg而非2 mg巴瑞替尼的次要结局更优。但巴瑞替尼组患者中痤疮、肌酸激酶水平升高，以及低密度和高密度脂蛋白胆固醇水平升高的发生率均显著高于安慰剂组。

研究结果表明，在涉及严重斑秃患者的两项3期试验中，口服巴瑞替尼在36周时的毛发再生方面优于安慰剂。需要更长的试验来评估巴瑞替尼治疗斑秃的疗效和安全性。

附：英文原文

Title: Two Phase 3 Trials of Baricitinib for Alopecia Areata | NEJM

Author: Brett King, M.D., Ph.D.,, Manabu Ohyama, M.D., Ph.D.,, Ohsang Kwon, M.D., Ph.D.,, Abraham Zlotogorski, M.D.,, Justin Ko, M.D.,, Natasha A. Mesinkovska, M.D., Ph.D.,, Maria Hordinsky, M.D.,, Yves Dutronc, M.D.,, Wen-Shuo Wu, M.D.,, Jill McCollam, Pharm.D.,, Chiara Chiasserini, Sc.D.,, Guanglei Yu, Ph.D.,, Sarah Stanley, Ph.D.,, Katrin Holzwarth, M.D.,, Amy M. DeLozier, M.P.H.,, and Rodney Sinclair, M.D.

Issue&Volume: 2022-03-26

Abstract:

Background

Alopecia areata is an autoimmune condition characterized by rapid hair loss in the scalp, eyebrows, and eyelashes, for which treatments are limited. Baricitinib, an oral, selective, reversible inhibitor of Janus kinases 1 and 2, may interrupt cytokine signaling implicated in the pathogenesis of alopecia areata.

Methods

We conducted two randomized, placebo-controlled, phase 3 trials (BRAVE-AA1 and BRAVE-AA2) involving adults with severe alopecia areata with a Severity of Alopecia Tool (SALT) score of 50 or higher (range, 0 [no scalp hair loss] to 100 [complete scalp hair loss]). Patients were randomly assigned in a 3:2:2 ratio to receive once-daily baricitinib at a dose of 4 mg, baricitinib at a dose of 2 mg, or placebo. The primary outcome was a SALT score of 20 or less at week 36.

Results

We enrolled 654 patients in the BRAVE-AA1 trial and 546 in the BRAVE-AA2 trial. The estimated percentage of patients with a SALT score of 20 or less at week 36 was 38.8% with 4-mg baricitinib, 22.8% with 2-mg baricitinib, and 6.2% with placebo in BRAVE-AA1 and 35.9%, 19.4%, and 3.3%, respectively, in BRAVE-AA2. In BRAVE-AA1, the difference between 4-mg baricitinib and placebo was 32.6 percentage points (95% confidence interval [CI], 25.6 to 39.5), and the difference between 2-mg baricitinib and placebo was 16.6 percentage points (95% CI, 9.5 to 23.8) (P<0.001 for each dose vs. placebo). In BRAVE-AA2, the corresponding values were 32.6 percentage points (95% CI, 25.6 to 39.6) and 16.1 percentage points (95% CI, 9.1 to 23.2) (P<0.001 for each dose vs. placebo). Secondary outcomes for baricitinib at a dose of 4 mg but not at a dose of 2 mg generally favored baricitinib over placebo. Acne, elevated levels of creatine kinase, and increased levels of low- and high-density lipoprotein cholesterol were more common with baricitinib than with placebo.

Conclusions

In two phase 3 trials involving patients with severe alopecia areata, oral baricitinib was superior to placebo with respect to hair regrowth at 36 weeks. Longer trials are required to assess the efficacy and safety of baricitinib for alopecia areata.

DOI: 10.1056/NEJMoa2110343

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2110343