巴瑞替尼用于对传统合成改善病情抗风湿药反应不足或不耐受的患者：RA-BUILD研究结果
Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study.
作者信息
Dougados Maxime, van der Heijde Désirée, Chen Ying-Chou, Greenwald Maria, Drescher Edit, Liu Jiajun, Beattie Scott, Witt Sarah, de la Torre Inmaculada, Gaich Carol, Rooney Terence, Schlichting Douglas, de Bono Stephanie, Emery Paul
机构信息
Department of Rheumatology, Paris Descartes University, Hôpital Cochin, Assistance Publique, Hôpitaux de Paris, INSERM (U1151), Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris, France.
Leiden University Medical Center, Leiden, The Netherlands.
出版信息
Ann Rheum Dis. 2017 Jan;76(1):88-95. doi: 10.1136/annrheumdis-2016-210094. Epub 2016 Sep 29.
BACKGROUND
Baricitinib is an oral, reversible, selective Janus kinase 1 and 2 inhibitor.
METHODS
In this phase III, double-blind 24-week study, 684 biologic disease-modifying antirheumatic drug (DMARD)-naïve patients with rheumatoid arthritis and inadequate response or intolerance to ≥1 conventional synthetic DMARDs were randomly assigned 1:1:1 to placebo or baricitinib (2 or 4 mg) once daily, stratified by region and the presence of joint erosions. Endpoint measures included American College of Rheumatology 20% response (ACR20, primary endpoint), Disease Activity Score (DAS28) and Simplified Disease Activity Index (SDAI) score ≤3.3.
RESULTS
More patients achieved ACR20 response at week 12 with baricitinib 4 mg than with placebo (62% vs 39%, p≤0.001). Compared with placebo, statistically significant improvements in DAS28, SDAI remission, Health Assessment Questionnaire-Disability Index, morning joint stiffness, worst joint pain and worst tiredness were observed. In a supportive analysis, radiographic progression of structural joint damage at week 24 was reduced with baricitinib versus placebo. Rates of adverse events during the treatment period and serious adverse events (SAEs), including serious infections, were similar among groups (SAEs: 5% for baricitinib 4 mg and placebo). One patient had an adverse event of tuberculosis (baricitinib 4 mg); one patient had an adverse event of non-melanoma skin cancer (baricitinib 4 mg). Two deaths and three major adverse cardiovascular events occurred (placebo). Baricitinib was associated with a decrease in neutrophils and increases in low-density and high-density lipoprotein.
CONCLUSIONS
In patients with rheumatoid arthritis and an inadequate response or intolerance to conventional synthetic DMARDs, baricitinib was associated with clinical improvement and inhibition of progression of radiographic joint damage.
TRIAL REGISTRATION NUMBER
NCT01721057; Results.
背景
巴瑞替尼是一种口服、可逆、选择性的 Janus 激酶 1 和 2 抑制剂。
方法
在这项为期 24 周的 III 期双盲研究中，684 例初治的类风湿关节炎患者，对≥1 种传统合成抗风湿药物（DMARDs）反应不足或不耐受，按地区和关节侵蚀情况分层，以 1:1:1 的比例随机分配至安慰剂组或每日一次服用巴瑞替尼（2 或 4mg）组。终点指标包括美国风湿病学会 20%反应率（ACR20，主要终点）、疾病活动评分（DAS28）和简化疾病活动指数（SDAI）评分≤3.3。
结果
在第 12 周时，服用 4mg 巴瑞替尼的患者达到 ACR20 反应的人数多于服用安慰剂的患者（62%对 39%，p≤0.001）。与安慰剂相比，观察到 DAS28、SDAI 缓解、健康评估问卷残疾指数、晨僵、最严重关节疼痛和最严重疲劳有统计学显著改善。在一项支持性分析中，与安慰剂相比，巴瑞替尼可降低第 24 周时关节结构损伤的影像学进展。治疗期间不良事件和严重不良事件（SAEs）发生率，包括严重感染，在各组间相似（SAEs：4mg 巴瑞替尼组和安慰剂组均为 5%）。1 例患者发生结核不良事件（4mg 巴瑞替尼组）；1 例患者发生非黑色素瘤皮肤癌不良事件（4mg 巴瑞替尼组）。发生 2 例死亡和 3 例主要不良心血管事件（安慰剂组）。巴瑞替尼与中性粒细胞减少以及低密度和高密度脂蛋白增加有关。
结论
在对传统合成 DMARDs 反应不足或不耐受的类风湿关节炎患者中，巴瑞替尼与临床改善及抑制影像学关节损伤进展相关。
试验注册号
NCT01721057；结果
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