在第三期SELECT-AXIS项目中，一种Janus激酶抑制剂Upadacitinib在强直性脊柱炎（AS）患者中显示出有效性和可接受的安全性。我们报告了SELECT-AXIS 2研究中AS患者（对生物治疗疾病改善抗风湿药物不足反应（bDMARD-IR））在1年内的疗效和安全性。年满18岁的活动性AS患者符合AS的修正纽约标准，并且对bDMARD-IR，接受双盲Upadacitinib每日15mg（QD）或安慰剂治疗14周。完成14周的患者可进入开放标签延长期并接受Upadacitinib每日15mg QD治疗最多2年。疗效终点包括在评估脊柱关节炎国际协会反应ASAS40、强直性脊柱炎疾病活动评分ASDAS低疾病活动（LDA）和ASDAS无病活动（ID）中达到≥40%改善的患者百分比；以及基线的总背痛综合评分、夜间背痛综合评分和巴斯强直性脊柱炎功能指数（BASFI）的改变。进行了亚组分析（bDMARD疗效不足 vs 忍受不良，以及之前的肿瘤坏死因子抑制剂[TNFi] vs 白细胞介素17抑制剂[IL-17i]接触）。针对二分类和连续疗效终点进行了使用非反应者插补（NRI-MI）和观察（AO）分析的评估；以及使用混合效应模型重复测量（MMRM）和AO分析的评估。根据不良事件进行了安全性评估。报道了截至52周的数据。在随机分配的420名患者中，有366人（持续Upadacitinib组：n=181；从安慰剂到Upadacitinib组：n=185）完成了52周的治疗。在52周时，持续Upadacitinib组和从安慰剂到Upadacitinib组，ASAS40、ASDAS LDA和ASDAS ID的达标率分别为66%和65%、57%和55%以及26%和25%（均为NRI-MI）；总背痛综合评分、夜间背痛综合评分和BASFI的改变分别为-4.5和-4.3、-4.6和-4.4以及-3.6和-3.5（均为MMRM）。未发现新的安全风险。亚组分析与整体研究人群一致。Upadacitinib每日15mg QD在bDMARD-IR患者中显示出持续的疗效改善达到52周。疗效在对bDMARD疗效不足和忍受不良以及之前的TNFi和IL-17i暴露的患者中普遍相似。NCT02049138.©2023. BioMed Central Ltd., Springer Nature的一部分。

Upadacitinib, a Janus kinase inhibitor, has demonstrated efficacy and an acceptable safety profile in patients with ankylosing spondylitis (AS) in the phase III SELECT-AXIS programs. We report the 1-year efficacy and safety in patients with AS and an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD-IR) from the SELECT-AXIS 2 study.Patients ≥ 18 years with active AS who met the modified New York criteria for AS and were bDMARD-IR received double-blind upadacitinib 15 mg once daily (QD) or placebo for 14 weeks. Patients who completed 14 weeks could enter an open-label extension and receive upadacitinib 15 mg QD for up to 2 years. Efficacy endpoints included the percentage of patients achieving ≥ 40% improvement in Assessment of SpondyloArthritis international Society response (ASAS40), Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity (LDA), and ASDAS inactive disease (ID); and change from baseline in total and nocturnal back pain, and Bath Ankylosing Spondylitis Functional Index (BASFI). Subgroup analyses (bDMARD lack of efficacy versus intolerance, and prior tumor necrosis factor inhibitor [TNFi] versus interleukin-17 inhibitor [IL-17i] exposure) were conducted. Binary and continuous efficacy endpoints were assessed using non-responder imputation with multiple imputation (NRI-MI) and as observed (AO) analyses; and mixed-effects model repeated measures (MMRM) and AO, respectively. Safety was assessed based on adverse events. Data through week 52 are reported.Of 420 randomized patients, 366 (continuous upadacitinib: n = 181; placebo to upadacitinib: n = 185) completed 52 weeks of treatment. At week 52, in the continuous upadacitinib and placebo to upadacitinib groups, ASAS40, ASDAS LDA, and ASDAS ID were achieved by 66% and 65%, 57% and 55%, and 26% and 25% (all NRI-MI); and change from baseline in total back pain, nocturnal back pain, and BASFI was -4.5 and -4.3, -4.6 and -4.4, and -3.6 and -3.5 (all MMRM), respectively. No new safety risks were identified. Subgroup analyses were consistent with the overall study population.Upadacitinib 15 mg QD demonstrated sustained improvement up to 52 weeks in bDMARD-IR patients with AS. Efficacy was generally similar in patients with lack of efficacy versus intolerance to bDMARDs and prior TNFi versus IL-17i exposure.NCT02049138.© 2023. BioMed Central Ltd., part of Springer Nature.