每日一次服用2毫克巴瑞替尼长期治疗活动性类风湿关节炎患者的疗效：两项24周III期随机对照研究及一项长期扩展研究的事后分析
Efficacy of Long-Term Treatment with Once-Daily Baricitinib 2 mg in Patients with Active Rheumatoid Arthritis: Post Hoc Analysis of Two 24-Week, Phase III, Randomized, Controlled Studies and One Long-Term Extension Study.
作者信息
Wells Alvin F, Jia Bochao, Xie Li, Valenzuela Guillermo J, Keystone Edward C, Li Zhanguo, Quebe Amanda K, Griffing Kirstin, Otawa Susan, Haraoui Boulos
机构信息
Aurora Rheumatology and Immunotherapy Center, Franklin, WI, USA.
Eli Lilly and Company, Lilly Technology Center South, 1555 South Harding Street, Indianapolis, IN, 46221, USA.
出版信息
Rheumatol Ther. 2021 Jun;8(2):987-1001. doi: 10.1007/s40744-021-00317-9. Epub 2021 May 24.
INTRODUCTION
To evaluate long-term efficacy of once-daily baricitinib 2 mg in patients with active rheumatoid arthritis who had an inadequate response (IR) to conventional synthetic disease-modifying antirheumatic drugs (csDMARD) or biologic DMARDs (bDMARD).
METHODS
Data from patients treated with baricitinib 2 mg daily in two 24-week, phase III studies, RA-BUILD (csDMARD-IR; NCT01721057) and RA-BEACON (bDMARD-IR; NCT01721044), and one long-term extension study (RA-BEYOND; NCT01885078), were analyzed (120 weeks). The main outcomes were achievement of low-disease activity (LDA; Simple Disease Activity Index [SDAI] ≤ 11), clinical remission (SDAI ≤ 3.3), Health Assessment Questionnaire Disability Index (HAQ-DI) ≤ 0.5 and improvement from baseline of ≥ 0.22, and safety. Analysis populations included (1) all patients and (2) never-rescued patients. Completer and non-responder imputation (NRI) analyses were conducted on each population.
RESULTS
In RA-BUILD, 684 were randomized (229 to baricitinib 2 mg, 180 of whom completed RA-BUILD and entered RA-BEYOND). In RA-BEACON, 527 were randomized (174 to baricitinib 2 mg, 117 of whom completed RA-BEACON and entered RA-BEYOND). In RA-BUILD-BEYOND, 85.1% (63/74, completer) and 27.5% (63/229, NRI) of csDMARD-IR patients treated with baricitinib 2 mg achieved SDAI LDA; 40.5% (30/74, completer) and 13.1% (30/229, NRI) were in SDAI remission; 62.2% (46/74, completer) and 20.1% (46/229, NRI) had HAQ-DI ≤ 0.5 and 81.1% (60/74, completer); and 26.2% (60/229, NRI) achieved ≥ 0.22 change from baseline at week 120. In RA-BEACON-BEYOND, 86.5% (32/37, completer) and 18.4% (32/174, NRI) of bDMARD-IR patients treated with baricitinib 2 mg achieved SDAI LDA; 24.3% (9/37, completer) and 5.2% (9/174, NRI) were in SDAI remission; 50.0% (19/38, completer) and 10.9% (19/174, NRI) had HAQ-DI ≤ 0.5; and 73.7% (28/38, completer) and 16.1% (28/174, NRI) achieved ≥ 0.22 change from baseline at week 120. Rates of adverse events of special interest were consistent with previous reports.
CONCLUSIONS
Long-term treatment with baricitinib 2 mg demonstrated efficacy for up to 120 weeks and was well tolerated.
TRIAL REGISTRATION
ClinicalTrials.gov identifier, NCT01721057, NCT01721044, and NCT01885078.
引言
评估每日一次服用2毫克巴瑞替尼对传统合成抗风湿药物（csDMARD）或生物抗风湿药物（bDMARD）反应不足（IR）的活动性类风湿关节炎患者的长期疗效。
方法
分析了两项为期24周的III期研究RA-BUILD（csDMARD-IR；NCT01721057）和RA-BEACON（bDMARD-IR；NCT01721044）以及一项长期扩展研究（RA-BEYOND；NCT01885078）中接受每日2毫克巴瑞替尼治疗的患者数据（120周）。主要结局包括达到低疾病活动度（LDA；简化疾病活动指数[SDAI]≤11）、临床缓解（SDAI≤3.3）、健康评估问卷残疾指数（HAQ-DI）≤0.5以及自基线改善≥0.22，以及安全性。分析人群包括（1）所有患者和（2）从未接受过救援治疗的患者。对每个人群进行了完整数据和无反应者插补（NRI）分析。
结果
在RA-BUILD研究中，684例患者被随机分组（229例接受2毫克巴瑞替尼治疗，其中180例完成RA-BUILD并进入RA-BEYOND研究）。在RA-BEACON研究中，527例患者被随机分组（174例接受2毫克巴瑞替尼治疗，其中117例完成RA-BEACON并进入RA-BEYOND研究）。在RA-BUILD-BEYOND研究中，接受2毫克巴瑞替尼治疗的csDMARD-IR患者中，85.1%（63/74，完整数据）和27.5%（63/229，NRI）达到SDAI-LDA；40.5%（30/74，完整数据）和13.1%（30/229，NRI）处于SDAI缓解状态；62.2%（46/74，完整数据）和20.1%（46/229，NRI）的HAQ-DI≤0.5，81.1%（60/74，完整数据）；以及26.2%（60/229，NRI）在第120周时自基线变化≥0.22。在RA-BEACON-BEYOND研究中，接受2毫克巴瑞替尼治疗的bDMARD-IR患者中，86.5%（32/37，完整数据）和18.4%（32/174，NRI）达到SDAI-LDA；24.3%（9/37，完整数据）和5.2%（9/174，NRI）处于SDAI缓解状态；50.0%（19/38，完整数据）和10.9%（19/174，NRI）的HAQ-DI≤0.5；以及73.7%（28/38，完整数据）和16.1%（28/174，NRI）在第120周时自基线变化≥0.22。特别关注的不良事件发生率与先前报告一致。
结论
长期服用2毫克巴瑞替尼治疗长达120周显示出疗效，且耐受性良好。
试验注册
ClinicalTrials.gov标识符，NCT01721057、NCT01721044和NCT01885078。
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