Jain Vipul, Giménez-Arnau Ana, Hayama Koremasa, Reich Adam, Carr Warner, Tillinghast Jeffrey, Dahale Swapnil, Lheritier Karine, Walsh Pauline, Zharkov Artem, Hugot Sophie, Haemmerle Sibylle
Division of Clinical Immunology and Allergy, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Department of Dermatology, Hospital del Mar Medical Research Institute, Universitat Pompeu Fabra, Barcelona, Spain.
J Allergy Clin Immunol. 2024 Feb;153(2):479-486.e4. doi: 10.1016/j.jaci.2023.10.007. Epub 2023 Oct 20.
Remibrutinib (LOU064), an oral, highly selective Bruton tyrosine kinase inhibitor, offers fast disease control in patients with chronic spontaneous urticaria (CSU) who remain symptomatic despite treatment with second-generation H1 antihistamines. It is currently in phase 3 development for CSU.
We sought to evaluate long-term safety and efficacy of remibrutinib in patients with CSU inadequately controlled with H antihistamines.
In this phase 2b extension study, patients who completed the core study and had a weekly Urticaria Activity Score (UAS7) ≥16 at the beginning of the extension study received remibrutinib 100 mg twice daily for 52 weeks. The primary objective was to assess long-term safety and tolerability. Key efficacy end points included change from baseline in UAS7 and proportion of patients with complete response to treatment (UAS7 = 0) and well-controlled disease (UAS7 ≤6) at week 4 and over 52 weeks.
Overall, 84.3% (194/230) of patients entered the treatment period and received ≥1 doses of remibrutinib. The overall safety profile of remibrutinib was comparable between the extension and core studies. Most treatment-emergent adverse events were mild to moderate and considered unrelated to remibrutinib by investigators. The 3 most common treatment-emergent adverse events by system organ class were infections (30.9%), skin and subcutaneous tissue (26.8%), and gastrointestinal disorders (16.5%). At week 4 and 52, mean ± SD change from baseline in UAS7 was -17.6 ± 13.40 and -21.8 ± 10.70; UAS7 = 0 (as observed) was achieved in 28.2% and 55.8% and UAS7 ≤6 (as observed) was achieved in 52.7% and 68.0% of patients, respectively.
Remibrutinib demonstrated a consistent favorable safety profile with fast and sustained efficacy for up to 52 weeks in patients with CSU.
瑞帕布替尼（LOU064）是一种口服的、高度选择性布鲁顿酪氨酸激酶抑制剂，对于尽管接受第二代H1抗组胺药治疗仍有症状的慢性自发性荨麻疹（CSU）患者，能实现快速的疾病控制。它目前正处于针对CSU的3期开发阶段。
我们试图评估瑞帕布替尼在H1抗组胺药控制不佳的CSU患者中的长期安全性和疗效。
在这项2b期扩展研究中，完成核心研究且在扩展研究开始时每周荨麻疹活动评分（UAS7）≥16的患者，接受每日两次100mg瑞帕布替尼治疗，持续52周。主要目的是评估长期安全性和耐受性。关键疗效终点包括UAS7较基线的变化，以及在第4周和52周时达到完全缓解（UAS7 = 0）和疾病得到良好控制（UAS7≤6）的患者比例。
总体而言，84.3%（194/230）的患者进入治疗期并接受了≥1剂瑞帕布替尼。瑞帕布替尼的总体安全性在扩展研究和核心研究中具有可比性。大多数治疗期间出现的不良事件为轻度至中度，研究者认为与瑞帕布替尼无关。按系统器官分类，3种最常见的治疗期间出现的不良事件为感染（30.9%）、皮肤和皮下组织（26.8%）以及胃肠道疾病（16.5%）。在第4周和52周时，UAS7较基线的平均变化±标准差分别为-17.6±13.40和-21.8±10.70；分别有28.2%和55.8%的患者达到UAS7 = 0（实际观察值），52.7%和68.0%的患者达到UAS7≤6（实际观察值）。
瑞帕布替尼在CSU患者中显示出持续良好的安全性，以及长达52周的快速和持续疗效。
