司库奇尤单抗改善非放射学中轴型脊柱关节炎患者报告的结局：Coast-X试验结果
Ixekizumab Improves Patient-Reported Outcomes in Non-Radiographic Axial Spondyloarthritis: Results from the Coast-X Trial.
作者信息
Deodhar Atul, Mease Philip, Rahman Proton, Navarro-Compán Victoria, Marzo-Ortega Helena, Hunter Theresa, Sandoval David, Kronbergs Andris, Leon Luis, Shan Mingyang, Leung Ann, De Vlam Kurt, Strand Vibeke
机构信息
Division of Arthritis and Rheumatic Diseases, Oregon Health and Science University, Portland, OR, USA.
Swedish Medical Center/Providence St. Joseph Health and University of Washington, Seattle, WA, USA.
出版信息
Rheumatol Ther. 2021 Mar;8(1):135-150. doi: 10.1007/s40744-020-00254-z. Epub 2020 Dec 7.
INTRODUCTION
Ixekizumab, an interleukin-17A antibody, has shown efficacy in non-radiographic axial spondyloarthritis (nr-axSpA). The objectives of this analysis were (a) to measure improvement in ixekizumab-treated patients in Assessment of Spondyloarthritis International Society (ASAS) response domains and other patient-reported outcomes (PROs) and (b) to determine how ASAS responses were associated with changes in patient global disease activity (PtGA), spinal pain, function, stiffness, fatigue, and spinal pain at night.
METHODS
COAST-X was a phase 3, 52-week multicenter, randomized, controlled trial investigating the efficacy and safety of 80-mg ixekizumab every 2 weeks (Q2W) and every 4 weeks (Q4W) in patients with active nr-axSpA. Changes from baseline in PROs were analyzed via mixed-effects models for repeated measures. Association analyses for ASAS responses used analysis of covariance with Scheffé's method.
RESULTS
Patients treated with ixekizumab Q2W and Q4W reported significantly greater improvements in PtGA, spinal pain, function, and stiffness at week 1, when these measures were first assessed, compared with placebo (p < 0.05). ASAS40 responders, in comparison to ASAS20 non-responders, had the highest correlations with improvements in all response domains (PtGA, spinal pain, function, and stiffness) as well as fatigue and spinal pain at night (p < 0.001). ASAS40 responses were associated with 3.5- to 48.0-fold greater improvements in these PROs, with the highest values for PtGA and function, compared to ASAS20 non-achievement.
CONCLUSIONS
As early as week 1, patients with nr-axSpA treated with ixekizumab reported significant improvements in PtGA, spinal pain, function, and stiffness compared with those taking placebo. ASAS40 responders reported significantly greater improvements in all ASAS response domains (PtGA, spinal pain, function, and stiffness) as well as fatigue and spinal pain at night than ASAS20 non-responders. Improvements in PtGA and function appear to be major drivers in achieving ASAS40 response in patients with nr-axSpA.
TRIAL REGISTRATION
NCT02757352.
引言
司库奇尤单抗是一种白细胞介素-17A抗体，已在非放射学中轴型脊柱关节炎（nr-axSpA）中显示出疗效。本分析的目的是：（a）测量接受司库奇尤单抗治疗的患者在国际脊柱关节炎评估协会（ASAS）反应领域和其他患者报告结局（PRO）方面的改善情况；（b）确定ASAS反应与患者总体疾病活动度（PtGA）、脊柱疼痛、功能、僵硬、疲劳及夜间脊柱疼痛变化之间的关联。
方法
COAST-X是一项为期52周的3期多中心随机对照试验，研究每2周（Q2W）和每4周（Q4W）皮下注射80mg司库奇尤单抗治疗活动性nr-axSpA患者的疗效和安全性。通过重复测量的混合效应模型分析PRO从基线的变化。ASAS反应的关联分析采用协方差分析和谢费方法。
结果
与安慰剂组相比，接受司库奇尤单抗Q2W和Q4W治疗的患者在第1周首次评估时，PtGA、脊柱疼痛、功能和僵硬方面的改善显著更大（p<0.05）。与ASAS20无反应者相比，ASAS40反应者在所有反应领域（PtGA、脊柱疼痛、功能和僵硬）以及疲劳和夜间脊柱疼痛方面的改善相关性最高（p<0.001）。与未达到ASAS20者相比，ASAS40反应者在这些PRO方面的改善幅度高3.5至48.0倍，PtGA和功能的改善值最高。
结论
早在第1周，接受司库奇尤单抗治疗的nr-axSpA患者与服用安慰剂的患者相比，在PtGA、脊柱疼痛、功能和僵硬方面有显著改善。ASAS40反应者在所有ASAS反应领域（PtGA、脊柱疼痛、功能和僵硬）以及疲劳和夜间脊柱疼痛方面的改善明显大于ASAS20无反应者。PtGA和功能的改善似乎是nr-axSpA患者达到ASAS40反应的主要驱动因素。
试验注册
NCT02757352。
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