Maurer Marcus, Berger William, Giménez-Arnau Ana, Hayama Koremasa, Jain Vipul, Reich Adam, Haemmerle Sibylle, Lheritier Karine, Walsh Pauline, Xia Summer, Storim Julian
Institute of Allergology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Allergology and Immunology, Berlin, Germany.
Southern California Research, Mission Viejo, Calif.
J Allergy Clin Immunol. 2022 Dec;150(6):1498-1506.e2. doi: 10.1016/j.jaci.2022.08.027. Epub 2022 Sep 9.
Chronic spontaneous urticaria (CSU) is inadequately controlled in many patients and greatly affects quality of life. Remibrutinib, a highly selective, oral, novel covalent Bruton tyrosine kinase inhibitor, might be effective in CSU.
This first-in-patient trial aimed to evaluate the efficacy and safety of remibrutinib in CSU treatment and characterize the dose-response.
This randomized, double-blind, placebo-controlled, phase 2b dose-finding trial evaluated remibrutinib (12 weeks) in patients inadequately controlled with second-generation H-antihistamines, with at least moderately active CSU, with or without prior anti-IgE treatment (NCT03926611). Patients received remibrutinib 10 mg once daily, 35 mg once daily, 100 mg once daily, 10 mg twice daily, 25 mg twice daily, 100 mg twice daily, or placebo (1:1:1:1:1:1:1 ratio). The main end points were weekly Urticaria Activity Score change from baseline at week 4 and safety.
Overall, 311 patients were randomized. Reduced symptom score was observed for all remibrutinib doses from week 1 until week 12, with weekly Urticaria Activity Score change from baseline at week 4: -19.1 (10 mg once daily), -19.1 (35 mg once daily), -14.7 (100 mg once daily), -16.0 (10 mg twice daily), -20.0 (25 mg twice daily), -18.1 (100 mg twice daily), and -5.4 for placebo (nominal P < .0001 for all doses vs placebo). Most adverse events were mild or moderate, with no dose-dependent pattern.
Remibrutinib was highly effective in the treatment of CSU over the entire dose range, with a rapid onset of action and a favorable safety profile.
许多慢性自发性荨麻疹（CSU）患者病情控制不佳，严重影响生活质量。瑞帕布替尼是一种高度选择性的口服新型共价布鲁顿酪氨酸激酶抑制剂，可能对CSU有效。
这项首例患者试验旨在评估瑞帕布替尼治疗CSU的疗效和安全性，并确定剂量反应关系。
这项随机、双盲、安慰剂对照的2b期剂量探索试验评估了瑞帕布替尼（12周）对第二代H1抗组胺药控制不佳、患有至少中度活动性CSU、有或无抗IgE治疗史的患者的疗效（NCT03926611）。患者接受每日一次10mg、每日一次35mg、每日一次100mg、每日两次10mg、每日两次25mg、每日两次100mg的瑞帕布替尼或安慰剂治疗（比例为1:1:1:1:1:1:1）。主要终点是第4周时每周荨麻疹活动评分相对于基线的变化以及安全性。
总体而言，311例患者被随机分组。从第1周直到第12周，所有瑞帕布替尼剂量组的症状评分均降低，第4周时每周荨麻疹活动评分相对于基线的变化分别为：每日一次10mg组-19.1、每日一次35mg组-19.1、每日一次100mg组-14.7、每日两次10mg组-16.0、每日两次25mg组-20.0、每日两次100mg组-18.1，安慰剂组为-5.4（所有剂量组与安慰剂组相比，名义P<0.0001）。大多数不良事件为轻度或中度，无剂量依赖性模式。
在整个剂量范围内，瑞帕布替尼治疗CSU疗效显著，起效迅速，安全性良好。
