Amsterdam University Medical Center, Amsterdam, The Netherlands.
Keio University School of Medicine, Tokyo, Japan.
Arthritis Rheumatol. 2020 Oct;72(10):1607-1620. doi: 10.1002/art.41384. Epub 2020 Sep 8.
The SELECT-EARLY trial was undertaken to study the effect of upadacitinib, an oral, reversible Janus kinase 1-selective inhibitor, as monotherapy in patients with predominantly early rheumatoid arthritis who were naive for or had limited exposure to methotrexate (MTX).
Patients (n = 947) were randomized 1:1:1 to receive once-daily doses of upadacitinib 15 mg or 30 mg or weekly MTX (7.5-20 mg/week) for 24 weeks. The primary end points were the proportion of patients who met the American College of Rheumatology 50% (ACR50) improvement criteria at week 12, and the proportion in whom a Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) of <2.6 was achieved at week 24. Data are presented through week 24.
At baseline, the median disease duration was 0.5 years (range 0-44 years). A total of 840 patients (89%) completed 24 weeks of treatment. The study met both primary end points for upadacitinib 15 mg and 30 mg versus MTX (ACR50 was achieved at week 12 in 52% and 56% of patients, respectively, versus 28% [P < 0.001], and DAS28-CRP <2.6 was achieved at week 24 in 48% and 50% of patients, respectively, versus 19% [P < 0.001]). Statistically significant and clinically meaningful improvements in multiple patient-reported outcomes (PROs) were recorded for both upadacitinib doses versus MTX. Overall, 88% of patients receiving upadacitinib 15 mg and 89% of patients receiving 30 mg, respectively, had no radiographic progression (modified total Sharp score ≤0) compared to 78% of those receiving MTX (P < 0.01). Through week 24, the frequency of treatment-emergent adverse events was similar between the MTX arm (65%) and upadacitinib 15 mg arm (64%), but was slightly higher in the upadacitinib 30 mg arm (71%). Six deaths were reported (2 in the upadacitinib 15 mg arm, 3 in the upadacitinib 30 mg arm, and 1 in the MTX arm).
Our findings indicate that patients receiving either dose of upadacitinib monotherapy experienced significant improvements in clinical, radiographic, and PROs compared to patients receiving MTX.
SELECT-EARLY 试验旨在研究口服、可逆的 Janus 激酶 1 选择性抑制剂乌帕替尼（upadacitinib）作为单药治疗主要处于早期阶段的类风湿关节炎患者的疗效，这些患者对甲氨蝶呤（methotrexate，MTX）初治或有限暴露。
947 例患者按 1:1:1 随机接受乌帕替尼 15 mg 或 30 mg 每日 1 次或每周 MTX（7.5-20 mg/周）治疗 24 周。主要终点为第 12 周达到美国风湿病学会 50%（ACR50）改善标准的患者比例，以及第 24 周达到疾病活动度评分 28 个关节（DAS28-CRP）<2.6 的患者比例。数据至第 24 周。
基线时，中位疾病病程为 0.5 年（范围 0-44 年）。共有 840 例（89%）患者完成了 24 周的治疗。该研究达到了乌帕替尼 15 mg 和 30 mg 与 MTX 相比的两个主要终点（分别有 52%和 56%的患者在第 12 周达到 ACR50，而 MTX 为 28%[P<0.001]，分别有 48%和 50%的患者在第 24 周达到 DAS28-CRP<2.6，而 MTX 为 19%[P<0.001]）。两种乌帕替尼剂量与 MTX 相比，患者报告的多个结局指标（PROs）均有显著且具有临床意义的改善。总体而言，与 MTX 组（78%）相比，分别接受乌帕替尼 15 mg 和 30 mg 的患者中，分别有 88%和 89%的患者没有影像学进展（改良总 Sharp 评分≤0）（P<0.01）。至第 24 周，MTX 组（65%）与乌帕替尼 15 mg 组（64%）的治疗中出现不良事件的频率相似，但乌帕替尼 30 mg 组（71%）略高。报告了 6 例死亡（乌帕替尼 15 mg 组 2 例，乌帕替尼 30 mg 组 3 例，MTX 组 1 例）。
我们的研究结果表明，与接受 MTX 治疗的患者相比，接受乌帕替尼单药治疗的患者在临床、影像学和 PROs 方面有显著改善。
