瑞米布替尼治疗慢性自发性荨麻疹，这一成果由柏林医学大学Marcus Maurer团队经过不懈努力而取得。2025年3月6日出版的《新英格兰医学杂志》发表了这项成果。

背景:慢性自发性荨麻疹是一种特发性综合征，表现为瘙痒、荨麻疹或血管性水肿（或这些症状的组合）持续6周以上。Remibrutinib是一种口服、高选择性布鲁顿酪氨酸激酶抑制剂，在2b期试验中显示出良好的疗效和安全性。需要来自3期试验的数据。

方法:在相同的、多中心、双盲、随机、安慰剂对照的REMIX-1和REMIX-2试验中，小组评估了remibrutinib在接受第二代h1 -抗组胺药治疗后对有症状的慢性自发性荨麻疹患者的疗效和安全性。患者以2:1的比例随机分配，接受25毫克口服瑞米鲁替尼，每日两次或安慰剂。主要终点是在7天期间从基线到第12周的荨麻疹活动评分（UAS7）的变化，其中包括1周内瘙痒和荨麻疹的严重程度评分（评分范围从0到42，分数越高表示严重程度越高）。关键次要终点包括不良事件，第2周和第12周的UAS7为6或更低，第12周的UAS7为0。

结果:共有470名REMIX-1患者和455名REMIX-2患者被随机分配接受remibrutinib（分别为313例和300例）或安慰剂（分别为157例和155例）。remibrutinib组在第12周的UAS7下降明显大于安慰剂组（最小二乘平均[±SE]变化，REMIX-1为- 20.0±0.7比- 13.8±1.0 [P<0.001]， REMIX-2为- 19.4±0.7比- 11.7±0.9 [P<0.001]），似乎持续到第24周。在第12周，瑞米布鲁替尼组的UAS7为6或更低的患者明显多于安慰剂组(REMIX-1, 49.8%对24.8% [P<0.001]；REMIX-2, 46.8% vs. 19.6% [P<0.001])， UAS7为0 (REMIX-1, 31.1% vs. 10.5% [P<0.001]；REMIX-2, 27.9% vs. 6.5% [P<0.001])。在瑞米鲁替尼组和安慰剂组中，有任何不良事件和严重不良事件的患者比例相似，尽管瑞米鲁替尼组中有瘀点的患者比例高于安慰剂组（3.8%比0.3%）。

研究结果表明，口服remibrutinib治疗导致第12周瘙痒和荨麻疹的综合测量显着改善。

附：英文原文

Title: Remibrutinib in Chronic Spontaneous Urticaria

Author: Martin Metz, Ana Giménez-Arnau, Michihiro Hide, Mark Lebwohl, Giselle Mosnaim, Sarbjit Saini, Gordon Sussman, Robert Szalewski, Sibylle Haemmerle, Karine Lheritier, El-Djouher Martzloff, Noriko Seko, Pengpeng Wang, Artem Zharkov, Marcus Maurer

Issue&Volume: 2025-03-06

Abstract: BACKGROUND

Chronic spontaneous urticaria is an idiopathic syndrome defined by recurring itch, hives, or angioedema (or a combination of these symptoms) for more than 6 weeks. Remibrutinib, an oral, highly selective Bruton’s tyrosine kinase inhibitor, showed efficacy and favorable safety in phase 2b trials. Data from phase 3 trials are needed.

METHODS

In the identical, multicenter, double-blind, randomized, placebo-controlled REMIX-1 and REMIX-2 trials, we evaluated the efficacy and safety of remibrutinib in patients with symptomatic chronic spontaneous urticaria after treatment with second-generation H1-antihistamines. Patients were randomly assigned in a 2:1 ratio to receive oral remibrutinib at a dose of 25 mg twice daily or placebo. The primary end point was the change from baseline to week 12 in the urticaria activity score during a 7-day period (UAS7), which comprises severity scores for itch and hives during 1 week (scores range from 0 to 42, with higher scores indicating greater severity). Key secondary end points included adverse events and a UAS7 of 6 or lower at weeks 2 and 12 and a UAS7 of 0 at week 12.

RESULTS

A total of 470 patients in REMIX-1 and 455 in REMIX-2 were randomly assigned to receive either remibrutinib (313 and 300 patients, respectively) or placebo (157 and 155 patients, respectively). The remibrutinib group had a significantly greater decrease in the UAS7 at week 12 than the placebo group (least-squares mean [±SE] change, 20.0±0.7 vs. 13.8±1.0 [P<0.001] in REMIX-1 and 19.4±0.7 vs. 11.7±0.9 [P<0.001] in REMIX-2), which appeared to be sustained through week 24. At week 12, significantly more patients in the remibrutinib group than in the placebo group had a UAS7 of 6 or lower (REMIX-1, 49.8% vs. 24.8% [P<0.001]; REMIX-2, 46.8% vs. 19.6% [P<0.001]) and a UAS7 of 0 (REMIX-1, 31.1% vs. 10.5% [P<0.001]; REMIX-2, 27.9% vs. 6.5% [P<0.001]). The percentages of patients with any adverse event and with serious adverse events were similar in the remibrutinib group and the placebo group, although a higher percentage of patients in the remibrutinib group than in the placebo group had petechiae (3.8% vs. 0.3% in the combined groups).

CONCLUSIONS

Treatment with oral remibrutinib resulted in a significant improvement in a composite measure of itching and hives at week 12.

DOI: NJ202503063921009

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2408792