Early and long-term efficacy and safety of remibrutinib in patients with chronic spontaneous urticaria: 52-week data from the Phase 3 REMIX-1 and REMIX-2 studies

IF 0.3 4区医学

Revue Francaise d Allergologie Pub Date : 2025-03-22 DOI:10.1016/j.reval.2025.104305

F. Bérard , A.M. Giménez-Arnau , M. Metz , M. Hide , V. Jain , A. Khemis , M. Lebwohl , M. Palumbo , S. Saini , E. Savk , G. Sussman , R. Szalewski , I. Walecka Herniczek , H. Windom , B. Yang , S. Haemmerle , K. Lheritier , P.G.P. Machado , E.D. Martzloff , N. Seko , M. Maurer

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引用次数: 0

Abstract

Prérequis/contexte

Remibrutinib (REM) is an oral, highly selective Bruton's tyrosine kinase inhibitor that has shown superior efficacy vs placebo (Pbo) and favorable safety in the primary analysis of the Phase 3 REMIX-1/-2 studies in patients with chronic spontaneous urticaria (CSU) inadequately controlled with H1-antihistamines (AH).

Objectifs

Herein we report the outcome over 52 weeks, including a post-hoc analysis for week (Wk) 1.

Méthodes

Patients were randomised 2: 1 to REM 25 mg twice daily (bid) or Pbo over a 24-week double-blind (DB) period, followed by 28 weeks open-label treatment with REM 25 mg bid for all patients. The primary endpoints were change from baseline (CFB) at Wk 12 in weekly Urticaria Activity Score (UAS7) and weekly Itch and Hives Severity Scores (ISS7/HSS7). Endpoints were also assessed at Wks 1, 24 and 52, along with adverse events (AEs) throughout the study.

Résultats/discussions

A total of 470 patients (REM n = 313; Pbo, n = 157) and 455 patients (REM n = 300; Pbo n = 155) were randomised in REMIX-1/-2, respectively. At Wk 1, for CFB-UAS7, REM showed significantly greater improvements vs Pbo (mean CFB-UAS7 in REMIX-1: −11.28 vs −4.04, in REMIX-2: −11.26 vs −2.90). REM demonstrated superiority at Wk 12 and improvements were sustained up to Wk 52 in the REM arm (mean CFB-UAS7 in REMIX-1: −23.2; in REMIX-2: −23.0). Significant improvement in the proportion of patients achieving UAS7 ≤ 6 was observed as early as Wk 1 with REM vs Pbo in REMIX-1/-2 (P = 0.001). At Wk 12 and up to Wk 52, statistically significantly more patients achieved UAS7 ≤ 6 and UAS7 = 0 with REM vs Pbo in both studies. In patients switching to REM at Wk 24, improvements were observed, in line with REM arm results. REM was well tolerated with long-term treatment up to Wk 52, with no increase in exposure adjusted incidence rates of AEs/SAEs during the entire study period vs 24-week DB period.

Conclusion

REM showed fast efficacy as early as Wk 1, with further improvements at Wk 12, sustained up to Wk 52, with a favorable safety profile in the REMIX-1/-2 studies. REM has the potential to be an effective novel oral treatment option for CSU patients inadequately controlled with AH.

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remibrutinib在慢性自发性荨麻疹患者中的早期和长期疗效和安全性：来自REMIX-1和REMIX-2研究的52周数据

emibrutinib （REM）是一种口服，高选择性布鲁顿酪氨酸激酶抑制剂，在3期REMIX-1/ 2研究中显示出优于安慰剂（Pbo）的疗效和良好的安全性，用于慢性自发性荨麻疹（CSU）患者，这些患者没有充分使用h -抗组胺药（AH）控制。在本文中，我们报告了52周的结果，包括第1周的事后分析。在为期24周的双盲（DB）研究期间，患者被随机分为2组：1组，REM组25毫克，每日两次（bid）或Pbo组，随后对所有患者进行为期28周的开放标签治疗，REM组25毫克，bid。主要终点是第12周时每周荨麻疹活动评分（UAS7）和每周瘙痒和荨麻疹严重程度评分（ISS7/HSS7）的基线变化（CFB）。终点也在第1、24和52周进行评估，以及整个研究过程中的不良事件（ae）。共470例患者(REM n = 313；Pbo, n = 157)和455例(REM n = 300；分别在REMIX-1/ 2中随机分配Pbo n = 155)。在第1周，与Pbo相比，CFB-UAS7的REM表现出更大的改善（REMIX-1的平均CFB-UAS7: - 11.28 vs - 4.04， REMIX-2的平均CFB-UAS7: - 11.26 vs - 2.90）。REM组在第12周表现出优势，改善持续到第52周(REMIX-1组的平均CFB-UAS7:−23.2；在REMIX-2:−23.0)。在REMIX-1/ 2中，早在第1周REM与Pbo中，就达到了UAS7≤6的患者比例的显著改善（P = 0.001）。在第12周和第52周，两项研究中，REM与Pbo中达到UAS7≤6和UAS7 = 0的患者数量均有统计学意义。在第24周切换到REM的患者中，观察到改善，与REM组的结果一致。长期治疗至第52周，REM耐受性良好，与24周DB期相比，整个研究期间暴露调整的ae / sae发生率没有增加。在REMIX-1/ 2研究中，rem早在第1周就显示出快速疗效，在第12周进一步改善，持续到第52周，具有良好的安全性。快速眼动有可能成为一种有效的新型口服治疗选择，用于不充分控制AH的CSU患者。

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来源期刊

Revue Francaise d Allergologie Medicine-Immunology and Allergy

自引率

33.30%

发文量

349

期刊介绍： La Revue Française d''Allergologie : un véritable forum pour faire connaître des travaux originaux et permettre la diffusion de l''information auprès de toutes les spécialités concernées par les pathologies allergiques. La Revue Française d''Allergologie (8 numéros par an) est au carrefour de nombreuses spécialités - dermatologie, pédiatrie, ORL, pneumologie, ophtalmologie, médecine interne - qui, toutes, ont à traiter des maladies allergiques. Les symptômes des allergies fondés sur des mécanismes communs sont le plus souvent associés et se succèdent chez un même patient. En forte progression depuis 20 ans, les maladies allergiques sont dans l''attente de perfectionnements et d''avancées thérapeutiques qui permettront aux nombreux patients qui en sont atteints de mieux vivre avec leurs allergies. La Revue Française d''Allergologie se veut donc un véritable forum de discussions et d''échanges entre tous les spécialistes confrontés aux pathologies