瑞士圣加仑州立医院Andrea Rubbert-Roth团队比较了Upadacitinib或阿巴西普治疗类风湿关节炎的临床疗效。2020年10月15日，该研究发表在《新英格兰医学杂志》上。

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。与阿巴西普（一种T细胞共刺激调节剂）相比，Upadacitinib治疗生物性改良性抗风湿药（DMARDs）难治性类风湿性关节炎患者，其疗效和安全性尚不清楚。

在这项为期24周的临床3期双盲对照试验中，研究组招募生物性DMARDs难治的类风湿性关节炎患者，将其按1：1随机分组，其中303例接受upadacitinib口服治疗，309例接受静脉输注阿巴西普治疗，每一种均与稳定的合成DMARDs联合使用。主要终点是根据第12周C反应蛋白水平来评估28项关节炎综合疾病活动评分与基线相比的变化，并评估非劣效性。

Upadacitinib组和阿巴西普组基线时DAS28-CRP值分别为5.70和5.88，治疗第12周时，评分分别降低了2.52和2.00，差异显著。Upadacitinib组中有30.0%的患者获得缓解，显著高于阿巴西普组（13.3%）。在治疗期间，Upadacitinib组中发生1例死亡、1例非致命性卒中和2例静脉血栓栓塞事件，Upadacitinib组与阿巴西普组相比，有更多的患者肝转氨酶水平升高。

研究结果表明，对于生物性DMARD难治的类风湿关节炎患者，采用Upadacitinib治疗显著优于阿巴西普，但严重不良事件发生率高。

附：英文原文

Title: Trial of Upadacitinib or Abatacept in Rheumatoid Arthritis

Author: Andrea Rubbert-Roth, M.D.,, Jeffrey Enejosa, M.D.,, Aileen L. Pangan, M.D.,, Boulos Haraoui, M.D.,, Maureen Rischmueller, M.B., B.S.,, Nasser Khan, M.D.,, Ying Zhang, Ph.D.,, Naomi Martin, M.D.,, and Ricardo M. Xavier, M.D.

Issue&Volume: 2020-10-14

Abstract:

Background

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.

Methods

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.

Results

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.

Conclusions

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.

DOI: 10.1056/NEJMoa2008250

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2008250