荷兰莱顿大学医学中心Désirée van der Heijde课题组研究了Upadacitinib治疗活动期强直性脊柱炎患者的疗效和安全性。2019年11月12日，国际知名学术期刊《柳叶刀》发表了这一成果。

JAK通路是强直性脊柱炎潜在的治疗靶点。Upadacitinib是一类选择性的JAK1抑制剂。

2017年11月30日至2018年10月15日，研究组在20个国家的62个地点进行了这项多中心、随机、双盲、安慰剂对照、临床2/3期的研究，招募了187名活动期强直性脊柱炎患者，均符合修订版纽约标准，此前未接受过生物制剂类抗风湿药治疗，且至少对两种药物应答不足或不耐受非甾体抗炎药。将其按1：1随机分组，93例患者接受Upadacitinib治疗，每日口服15mg，94例患者接受安慰剂治疗。

共有178名（95%）患者完成了治疗。第14周，Upadacitinib组中有52%的患者获得国际脊柱关节炎学会评估改善40%，显著高于安慰剂组（26%）。Upadacitinib组和安慰剂组的不良事件发生率分别为62%和55%，其中最常见的不良反应为肌酸磷酸激酶升高，两组中的发生率分别为9%和2%。均未发生严重感染、带状疱疹、恶性肿瘤、静脉血栓栓塞或死亡事件，但每组均有1例严重不良事件发生。

总之，Upadacitinib治疗非甾体抗炎药应答不足或不耐受的活动期强直性脊柱炎患者有效且耐受性好。该数据支持Upadacitinib进一步去治疗中轴型脊柱炎。

附：英文原文

Title: Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomised, double-blind, placebo-controlled, phase 2/3 trial

Author: Désirée van der Heijde, In-Ho Song, Aileen L Pangan, Atul Deodhar, Filip van den Bosch, Walter P Maksymowych, Tae-Hwan Kim, Mitsumasa Kishimoto, Andrea Everding, Yunxia Sui, Xin Wang, Alvina D Chu, Joachim Sieper

Issue&Volume: November 12, 2019

Abstract:

Background

The JAK pathway is a potential therapeutic target in ankylosing spondylitis. This study assessed the efficacy and safety of upadacitinib, a selective JAK1 inhibitor, in patients with ankylosing spondylitis.

Methods

This multicentre, randomised, double-blind, placebo-controlled, two-period, parallel-group, phase 2/3 study, SELECT-AXIS 1, enrolled adults in 62 sites in 20 countries. Eligible patients had active ankylosing spondylitis, fulfilled modified New York criteria, were previously untreated with biological disease-modifying antirheumatic drugs, and had inadequate response to at least two or intolerance or contraindication to non-steroidal anti-inflammatory drugs. Patients were randomly assigned 1:1 using interactive response technology to take oral upadacitinib 15 mg once daily or oral placebo for the 14-week period 1; only period 1 data are reported here. The primary endpoint was the composite outcome measure of the Assessment of SpondyloArthritis international Society 40 response at week 14. Analyses were done in the full analysis set of patients who were randomly assigned and received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03178487.

Findings

Between Nov 30, 2017, and Oct 15, 2018, 187 patients were randomly assigned to upadacitinib 15 mg (93 patients) or to placebo (94 patients), and 178 (95%) patients (89 in the upadacitinib group and 89 in the placebo group) completed period 1 on study drug (by the completion date of Jan 21, 2019). Significantly more patients had an Assessment of SpondyloArthritis international Society 40 response in the upadacitinib group versus in the placebo group at week 14 (48 [52%] of 93 patients vs 24 [26%] of 94 patients; p=0·0003; treatment difference 26% [95% CI 13–40]). Adverse events were reported in 58 (62%) of 93 patients in the upadacitinib group versus 52 (55%) of 94 in the placebo group. The most common adverse event in the upadacitinib group was increased creatine phosphokinase (eight [9%] of 93 patients in the upadacitinib group vs two [2%] of 94 patients with placebo). No serious infections, herpes zoster, malignancy, venous thromboembolic events, or deaths were reported; one serious adverse event was reported in each group.

Interpretation

Upadacitinib 15 mg was efficacious and well tolerated in patients with active ankylosing spondylitis who had an inadequate response or contraindication to non-steroidal anti-inflammatory drugs. These data support the further investigation of upadacitinib for the treatment of axial spondyloarthritis.

DOI: 10.1016/S0140-6736(19)32534-6

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32534-6/fulltext