Aceituno D, Fawsitt C G, Power G M, Law E, Vaghela S, Thom H
Clifton Insight, Bristol, UK.
Pontificia Universidad Católica de Chile, Santiago, Chile.
J Eur Acad Dermatol Venereol. 2025 Jun;39(6):1134-1142. doi: 10.1111/jdv.20372. Epub 2024 Oct 24.
Ritlecitinib and baricitinib are recently approved systemic treatments for severe alopecia areata (AA). Both demonstrated superiority over placebo in hair regrowth measured by the Severity of Alopecia Tool (SALT), but they have not been directly compared in randomized controlled trials (RCTs). We conducted a systematic review of RCTs evaluating treatments in AA and estimated the efficacy and safety of ritlecitinib and baricitinib at Week 24 using Bayesian network meta-analysis. To adjust and explore effect modifiers, population-adjusted indirect comparison was performed via multilevel network meta-regression (ML-NMR) using ritlecitinib individual patient data (IPD). Co-primary endpoints were SALT ≤20 and SALT ≤10 at Week 24. Unanchored population adjusted ITCs were also computed to evaluate SALT ≤10 and SALT ≤20 endpoints at Week 48/52. Four RCTs (ALLEGRO 2a [NCT02974868], ALLEGRO 2b/3 [NCT03732807], BRAVE-AA1 [NCT03570749] and BRAVE-AA2 [NCT03899259]) were included. No evidence of a difference between ritlecitinib 50 mg and baricitinib 4 mg on SALT ≤10 (odds ratio, OR: 0.96, 95% credible interval, CrI: 0.18-7.21) and SALT ≤20 (OR: 2.16, 95% CrI: 0.48-16.46) at Week 24 was found. ML-NMR using ALLEGRO IPD adjusted for sex, SALT score at baseline, duration of current episode and disease duration found evidence of effect modification, although relative efficacy between ritlecitinib 50 mg and baricitinib 4 mg remained unchanged. Unanchored population-adjusted ITC at Week 48/52 was consistent with previous results. We found similar efficacy between ritlecitinib 50 mg and baricitinib 4 mg. These ITCs was informed by only four RCTs, uncertainty was considerable, and there was evidence of effect modification, highlighting the need for further quality research in AA.
利特昔替尼和巴瑞替尼是最近被批准用于治疗重度斑秃（AA）的全身性药物。在通过脱发严重程度工具（SALT）衡量的毛发再生方面，两者均显示出优于安慰剂的效果，但它们尚未在随机对照试验（RCT）中进行直接比较。我们对评估AA治疗方法的RCT进行了系统评价，并使用贝叶斯网络荟萃分析估计了利特昔替尼和巴瑞替尼在第24周时的疗效和安全性。为了调整和探索效应修饰因素，我们使用利特昔替尼的个体患者数据（IPD），通过多级网络荟萃回归（ML-NMR）进行了人群调整间接比较。共同主要终点是第24周时SALT≤20和SALT≤10。还计算了未锚定的人群调整ITC，以评估第48/52周时SALT≤10和SALT≤20的终点。纳入了四项RCT（ALLEGRO 2a [NCT02974868]、ALLEGRO 2b/3 [NCT03732807]、BRAVE-AA1 [NCT03570749]和BRAVE-AA2 [NCT03899259]）。未发现第24周时50mg利特昔替尼和4mg巴瑞替尼在SALT≤10（优势比，OR：0.96，95%可信区间，CrI：0.18 - 7.21）和SALT≤20（OR：2.16，95% CrI：0.48 - 16.46）方面存在差异。使用ALLEGRO IPD对性别、基线SALT评分、当前发作持续时间和疾病持续时间进行调整的ML-NMR发现了效应修饰的证据，尽管50mg利特昔替尼和4mg巴瑞替尼之间的相对疗效保持不变。第48/52周时未锚定的人群调整ITC与先前结果一致。我们发现50mg利特昔替尼和4mg巴瑞替尼之间疗效相似。这些ITC仅基于四项RCT得出，不确定性相当大，且存在效应修饰的证据，这突出表明在AA方面需要进一步的高质量研究。
