The efficacy and safety of upadacitinib in patients with ankylosing spondylitis (AS) and inadequate response/intolerance to biologic disease-modifying antirheumatic drugs (bDMARD-IR) were evaluated through 1 year in the SELECT-AXIS 2 study. Here, we assess 2-year efficacy, safety, and imaging outcomes in SELECT-AXIS 2. Patients who received continuous upadacitinib, and those who switched from placebo to upadacitinib at week 14, could enter the open-label extension (OLE). Efficacy endpoints included Assessment of SpondyloArthritis international Society (ASAS) and Axial Spondyloarthritis Disease Activity Score (ASDAS) responses, and changes from baseline in measures of disease activity, back pain, function, and quality of life. Radiographic progression was evaluated using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). As observed (AO) and AO with non-responder imputation (AO-NRI) analyses were used for binary endpoints; AO with mixed-effects model for repeated measures (AO-MMRM) for continuous endpoints; and AO-analysis of covariance for mSASSS. Treatment-emergent adverse events (TEAEs) in patients receiving ≥ 1 upadacitinib dose through week 104 are presented as events (E)/100 patient-years (PY). Subgroup analyses were performed by prior tumor necrosis factor/interleukin-17 inhibitor exposure and bDMARD lack of efficacy/intolerance. Of 420 patients who entered the bDMARD-IR AS study, 409 entered the OLE, and 331 (continuous upadacitinib, n = 163; placebo to upadacitinib, n = 168) completed week 104. Improvements in efficacy measures were sustained through the OLE, with similar response rates between the continuous upadacitinib and placebo to upadacitinib groups at week 104. At week 104, 64.9% and 61.7% of patients, respectively, had achieved ASAS 40% response (AO-NRI). Mean changes from baseline were similar between the two groups at week 104 across measures (ASDAS: -2.1 and -2.0; total back pain: -4.9 and -4.6, respectively; AO-MMRM). Over 93.0% of patients showed no radiographic progression (mSASSS mean change from baseline < 2) at week 104. The overall TEAE rate was 165.2 E/100 PY, with low rates of major adverse cardiovascular and venous thromboembolic events (0.3 E/100 PY each). Upadacitinib efficacy, including very low rates of radiographic progression, was demonstrated through 104 weeks in treatment-refractory patients with active AS. Treatment was well tolerated, with no newly identified safety signals. NCT04169373.

中文翻译：

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upadacitinib 在生物治疗难治性活动性强直性脊柱炎患者中的疗效和安全性：SELECT-AXIS 2 研究开放标签扩展的 2 年临床和影像学结果


在 SELECT-AXIS 2 研究中，对 upadacitinib 在强直性脊柱炎 （AS） 和对生物疾病缓解抗风湿药 （bDMARD-IR） 反应不足/不耐受患者中的疗效和安全性进行了 1 年评估。在这里，我们评估了 SELECT-AXIS 2 的 2 年疗效、安全性和影像学结果。接受连续 upadacitinib 治疗的患者以及在第 14 周从安慰剂转为 upadacitinib 的患者可以进入开放标签扩展 （OLE）。疗效终点包括国际脊柱关节炎协会 （ASAS） 和中轴型脊柱关节炎疾病活动评分 （ASDAS） 反应评估，以及疾病活动、背痛、功能和生活质量指标相对于基线的变化。使用改良的 Stoke 强直性脊柱炎脊髓评分 （mSASSS） 评估影像学进展。二元终点采用观察值 （AO） 和无反应者插补 （AO-NRI） 分析;连续终点的重复测量混合效应模型 （AO-MMRM） 的 AO;和 mSASSS 协方差的 AO 分析。在第 104 周接受 ≥ 1 剂 upadacitinib 的患者的治疗中出现的不良事件 （TEAE） 表示为事件 （E）/100 患者年 （PY）。通过既往肿瘤坏死因子/白细胞介素 17 抑制剂暴露和 bDMARD 缺乏疗效/不耐受进行亚组分析。在进入 bDMARD-IR AS 研究的 420 名患者中，409 名进入 OLE，331 名 （连续 upadacitinib，n = 163;安慰剂与 upadacitinib，n = 168）完成第 104 周。疗效指标的改善通过 OLE 持续存在，在第 104 周时，连续 upadacitinib 组和安慰剂组之间的反应率与 upadacitinib 组相似。在第 104 周，64.9% 和 61。分别有 7% 的患者达到 ASAS 40% 反应 （AO-NRI）。在第 104 周，两组相对于基线的平均变化在各项指标中相似 （ASDAS： -2.1 和 -2.0;总背痛： 分别为 -4.9 和 -4.6;AO-MMRM） 的超过 93.0% 的患者在第 104 周时没有显示影像学进展 （mSASSS 相对于基线 < 2 的平均变化）。总 TEAE 率为 165.2 E/100 PY，主要不良心血管和静脉血栓栓塞事件发生率较低 （每次 0.3 E/100 PY）。Upadacitinib 的疗效，包括极低的影像学进展率，在难治性活动性 AS 患者中通过 104 周得到证实。治疗耐受性良好，无新发现的安全信号。NCT04169373。