From the Division of Rheumatology, Cantonal Clinic St. Gallen, St. Gallen, Switzerland (A.R.-R.); AbbVie, North Chicago, IL (J.E., A.L.P., N.K., Y.Z., N.M.); Centre Hospitalier de l'Université de Montréal, Montreal (B.H.); Queen Elizabeth Hospital and University of Adelaide, Adelaide, SA, Australia (M.R.); and Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil (R.M.X.).
N Engl J Med. 2020 Oct 15;383(16):1511-1521. doi: 10.1056/NEJMoa2008250.
Upadacitinib is an oral selective Janus kinase inhibitor to treat rheumatoid arthritis. The efficacy and safety of upadacitinib as compared with abatacept, a T-cell costimulation modulator, in patients with rheumatoid arthritis refractory to biologic disease-modifying antirheumatic drugs (DMARDs) are unclear.
In this 24-week, phase 3, double-blind, controlled trial, we randomly assigned patients in a 1:1 ratio to receive oral upadacitinib (15 mg once daily) or intravenous abatacept, each in combination with stable synthetic DMARDs. The primary end point was the change from baseline in the composite Disease Activity Score for 28 joints based on the C-reactive protein level (DAS28-CRP; range, 0 to 9.4, with higher scores indicating more disease activity) at week 12, assessed for noninferiority. Key secondary end points at week 12 were the superiority of upadacitinib over abatacept in the change from baseline in the DAS28-CRP and the percentage of patients having clinical remission according to a DAS28-CRP of less than 2.6.
A total of 303 patients received upadacitinib, and 309 patients received abatacept. From baseline DAS28-CRP values of 5.70 in the upadacitinib group and 5.88 in the abatacept group, the mean change at week 12 was -2.52 and -2.00, respectively (difference, -0.52 points; 95% confidence interval [CI], -0.69 to -0.35; P<0.001 for noninferiority; P<0.001 for superiority). The percentage of patients having remission was 30.0% with upadacitinib and 13.3% with abatacept (difference, 16.8 percentage points; 95% CI, 10.4 to 23.2; P<0.001 for superiority). During the treatment period, one death, one nonfatal stroke, and two venous thromboembolic events occurred in the upadacitinib group, and more patients in the upadacitinib group than in the abatacept group had elevated hepatic aminotransferase levels.
In patients with rheumatoid arthritis refractory to biologic DMARDs, upadacitinib was superior to abatacept in the change from baseline in the DAS28-CRP and the achievement of remission at week 12 but was associated with more serious adverse events. Longer and larger trials are required in order to determine the effect and safety of upadacitinib in patients with rheumatoid arthritis. (Funded by AbbVie; SELECT-CHOICE Clinicaltrials.gov number, NCT03086343.).
Upadacitinib 是一种口服选择性 Janus 激酶抑制剂，用于治疗类风湿关节炎。在对生物改善病情抗风湿药（DMARDs）反应不佳的类风湿关节炎患者中，与 T 细胞共刺激调节剂阿巴西普相比，Upadacitinib 的疗效和安全性尚不清楚。
在这项为期 24 周、双盲、对照的 3 期临床试验中，我们以 1:1 的比例随机分配患者接受口服 Upadacitinib（每日一次 15mg）或静脉注射阿巴西普治疗，两种药物均与稳定的合成 DMARD 联合使用。主要终点是从基线开始的第 12 周时基于 C 反应蛋白水平的 28 个关节复合疾病活动评分（DAS28-CRP；范围为 0 至 9.4，分数越高表示疾病活动度越高）的变化，评估非劣效性。第 12 周的关键次要终点是与阿巴西普相比，Upadacitinib 从基线开始时在 DAS28-CRP 中的变化以及根据 DAS28-CRP 小于 2.6 确定的临床缓解率。
共有 303 名患者接受 Upadacitinib 治疗，309 名患者接受阿巴西普治疗。在 Upadacitinib 组和阿巴西普组的基线 DAS28-CRP 值分别为 5.70 和 5.88 时，第 12 周的平均变化分别为-2.52 和-2.00（差异，-0.52 点；95%置信区间 [CI]，-0.69 至 -0.35；P<0.001 非劣效性；P<0.001 优越性）。接受 Upadacitinib 治疗的患者缓解率为 30.0%，接受阿巴西普治疗的患者缓解率为 13.3%（差异为 16.8 个百分点；95%CI，10.4 至 23.2；P<0.001 优越性）。在治疗期间，Upadacitinib 组有 1 例死亡、1 例非致命性中风和 2 例静脉血栓栓塞事件，Upadacitinib 组的肝转氨酶升高患者多于阿巴西普组。
在对生物 DMARDs 反应不佳的类风湿关节炎患者中，与阿巴西普相比，Upadacitinib 在第 12 周时从基线开始的 DAS28-CRP 变化和缓解方面更具优势，但与更严重的不良事件相关。需要更长和更大规模的试验来确定 Upadacitinib 在类风湿关节炎患者中的疗效和安全性。（由 AbbVie 资助；SELECT-CHOICE 临床试验。gov 编号，NCT03086343。）
