Efficacy and safety of branebrutinib (BMS-986195), an irreversible Bruton's tyrosine kinase inhibitor, for the treatment of rheumatoid arthritis: a phase 2a, randomised, double-blind, placebo-controlled study.

This study assessed the efficacy and safety of branebrutinib in patients with rheumatoid arthritis and an inadequate response to methotrexate.

本研究评估了Branebrutinib在对甲氨蝶呤反应不足的类风湿性关节炎患者中的疗效和安全性。

Methods

This phase 2a, randomised, double-blind, placebo-controlledstudy was designed to assess the efficacy and safety of branebrutinib in patients with rheumatoid arthritis, systemic lupus erythematosus, or primary Sjögren's disease.

这项2a期、随机、双盲、安慰剂对照研究旨在评估Branebrutinib在类风湿性关节炎、系统性红斑狼疮或原发性干燥综合征患者中的疗效和安全性。

Here, we report the results of the rheumatoid arthritis substudy, done in the USA, Poland, and Spain across 24 sites.

在这里，我们报告了在美国、波兰和西班牙的24个地点进行的类风湿性关节炎子研究的结果。

The study included a 12-week double-blindtreatment period followed by an additional 12-week open-label period with abatacept treatment.

该研究包括了一个为期12周的双盲治疗期，随后是一个额外的为期12周的开放标签期，期间使用了abatacept治疗。

Only data for the double-blindtreatment period are reported here.

这里仅报告了双盲治疗期的数据。

Eligible patients were aged 18-75 years, met the 2010 American College of Rheumatology (ACR)-European Alliance of Associations for Rheumatology criteria for rheumatoid arthritis, had disease duration less than 4 years, and had inadequate response to methotrexate.

符合条件的患者年龄在18-75岁之间，符合2010年美国风湿病学会（ACR）-欧洲风湿病协会联盟的类风湿关节炎标准，病程少于4年，并且对甲氨蝶呤反应不足。

Patients were randomly assigned (3:1) to receive branebrutinib 9 mg once daily or placebo for 12 weeks.

患者被随机分配（3:1）接受每日一次9毫克的branebrutinib或安慰剂治疗，为期12周。

Randomisation was carried out centrally according to a computer-generated block randomisation scheme using interactive response technology.

随机化是根据计算机生成的分块随机化方案，通过交互式响应技术在中心进行的。

All parties were masked to treatment allocation.

所有相关方都对治疗分配进行了盲法处理。

The primary endpoint was the proportion of patients who had 50% improvement in the ACR response criteria (ACR50) at week 12, assessed in all participants randomly assigned to treatment (full analysis set).

主要终点是在第12周时，评估所有随机分配到治疗的参与者（完整分析集）中达到美国风湿病学会改善标准（ACR50）50%改善的患者比例。

Safety was assessed in patients who received at least one dose of branebrutinib or placebo.

安全性评估是在接受至少一次branebrutinib或安慰剂治疗的患者中进行的。

This trial was registered with ClinicalTrials.gov, NCT04186871.

该试验已在ClinicalTrials.gov注册，注册号为NCT04186871。

Patients with lived experience of rheumatoid arthritis were not involved in the study design.

未邀请有类风湿性关节炎生活经历的患者参与研究设计。

Results

Between Jan 7, 2020, to Dec 5, 2022, 85 patients were randomly assigned to receive branebrutinib (n=64) or placebo (n=21). 63 (74%) of 85 patients were female, 22 (26%) were male, 80 (94%) were White, and the mean age was 49·1 years (SD 12·0).

在2020年1月7日至2022年12月5日期间，85名患者被随机分配接受branebrutinib治疗(n=64)或安慰剂(n=21)。85名患者中有63名(74%)为女性，22名(26%)为男性，80名(94%)为白人，平均年龄为49.1岁（标准差12.0）。

The primary endpoint of ACR50 response at week 12 was not met; 12 (19%) of 64 patients had an ACR50 response in the branebrutinib group compared with seven (33%) of 21 patients in the placebo group (p=0·16).

主要终点ACR50反应在第12周未达到；branebrutinib组64名患者中有12名（19%）达到ACR50反应，而安慰剂组21名患者中有7名（33%）达到ACR50反应（p=0.16）。

Adverse events were similar between the two groups (30 [47%] of 64 in the branebrutinib group and 8 [38%] of 21 in the placebo group), with no reported serious adverse events or deaths.

两组之间的不良事件相似（64名患者中有30名（47%）在branebrutinib组和21名患者中有8名（38%）在安慰剂组），没有报告严重的不良事件或死亡。

interpretation

There was no significant difference between branebrutinib and placebo for any clinical efficacy measures.

branebrutinib和安慰剂在任何临床疗效指标上都没有显著差异。

The 12-week safety profiles were similar between treatment groups, and branebrutinib was well tolerated with a favourable safety profile.

治疗组之间的12周安全性概况相似，branebrutinib耐受性良好，具有良好的安全性特征。

funding

Bristol Myers Squibb.

百时美施贵宝公司。