Yale School of Medicine, New Haven, CT, USA.
Southern California Dermatology, Santa Ana, CA, USA.
Am J Clin Dermatol. 2024 Mar;25(2):299-314. doi: 10.1007/s40257-024-00846-3. Epub 2024 Jan 23.
The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib, an oral JAK3/TEC family kinase inhibitor, is efficacious at doses of ≥ 30 mg in patients aged ≥ 12 years with alopecia areata (AA).
The objective of this study was to evaluate the safety of ritlecitinib in an integrated analysis of four studies in AA.
Two cohorts were analyzed: a placebo-controlled and an all-exposure cohort. Proportions and study size-adjusted incidence rates (IRs) of adverse events (AEs) of interest and laboratory abnormalities are reported.
In the placebo-controlled cohort (n = 881; median exposure: 169 days), the proportion of ritlecitinib-treated patients with AEs was 70.2-75.4% across doses versus 69.5% in the placebo group; serious AEs occurred in 0-3.2% versus 1.9% for the placebo. A total of 19 patients permanently discontinued due to AEs (5 while receiving the placebo). In the all-exposure cohort (n = 1294), median ritlecitinib exposure was 624 days [2091.7 total patient-years (PY)]. AEs were reported in 1094 patients (84.5%) and serious AEs in 57 (4.4%); 78 (6.0%) permanently discontinued due to AEs. The most common AEs were headache (17.7%; 11.9/100 PY), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (15.5%; 9.8/100 PY), and nasopharyngitis (12.4%; 8.2/100 PY). There were two deaths (breast cancer and acute respiratory failure/cardiorespiratory arrest). Proportions (IRs) were < 0.1% (0.05/100 PY) for opportunistic infections, 1.5% (0.9/100 PY) for herpes zoster, 0.5% (0.3/100 PY) for malignancies (excluding nonmelanoma skin cancer), and 0.2% (0.1/100 PY) for major adverse cardiovascular events.
Ritlecitinib is well tolerated with an acceptable safety profile up to 24 months in patients aged ≥ 12 years with AA (video abstract and graphical plain language summary available).
ClinicalTrials.gov: NCT02974868 (date of registration: 11/29/2016), NCT04517864 (08/18/2020), NCT03732807 (11/07/2018), and NCT04006457 (07/05/2019).
ALLEGRO 期 2a 和 2b/3 研究表明，口服 JAK3/TEC 家族激酶抑制剂 ritlecitinib 在≥30mg 剂量下对年龄≥12 岁的斑秃患者有效。
本研究旨在通过对四项斑秃研究的综合分析，评估 ritlecitinib 的安全性。
分析了两个队列：安慰剂对照队列和全暴露队列。报告了感兴趣的不良事件（AE）和实验室异常的比例和研究规模调整后的发生率（IR）。
在安慰剂对照队列（n=881；中位暴露时间：169 天）中，接受 ritlecitinib 治疗的患者出现 AE 的比例为 70.2-75.4%，安慰剂组为 69.5%；安慰剂组有 0-3.2%的患者发生严重 AE。共有 19 名患者因 AE 永久停药（5 名在接受安慰剂治疗时停药）。在全暴露队列（n=1294）中，中位 ritlecitinib 暴露时间为 624 天[2091.7 总患者年（PY）]。1094 名患者（84.5%）报告了 AE，57 名（4.4%）发生严重 AE；78 名（6.0%）因 AE 永久停药。最常见的 AE 是头痛（17.7%；11.9/100 PY）、严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）阳性检测（15.5%；9.8/100 PY）和鼻咽炎（12.4%；8.2/100 PY）。有 2 例死亡（乳腺癌和急性呼吸衰竭/心肺骤停）。机会性感染的比例（IR）<0.1%（0.05/100 PY），带状疱疹为 1.5%（0.9/100 PY），恶性肿瘤（不包括非黑色素瘤皮肤癌）为 0.5%（0.3/100 PY），主要不良心血管事件为 0.2%（0.1/100 PY）。
在年龄≥12 岁的斑秃患者中，接受 ritlecitinib 治疗的患者在 24 个月内耐受性良好，安全性特征可接受（视频摘要和图形通俗语言摘要可用）。
ClinicalTrials.gov：NCT02974868（注册日期：2016 年 11 月 29 日）、NCT04517864（2020 年 8 月 18 日）、NCT03732807（2018 年 11 月 7 日）和 NCT04006457（2019 年 7 月 5 日）。
