Deodhar Atul A, Mease Philip J, Rahman Proton, Navarro-Compán Victoria, Strand Vibeke, Hunter Theresa, Bolce Rebecca, Leon Luis, Lauzon Steve, Marzo-Ortega Helena
Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, 3181 Sam Jackson Park Rd, Portland, OR, 97239, USA.
Swedish Medical Center/ Providence St. Joseph Health and University of Washington, Seattle, WA, USA.
BMC Rheumatol. 2021 Sep 20;5(1):35. doi: 10.1186/s41927-021-00205-3.
This analysis assessed improvements in patients with radiographic axial spondyloarthritis (r-axSpA) treated with ixekizumab in the Assessment of Spondyloarthritis International Society (ASAS) treatment response domains and additional patient-reported outcomes at 1 year of treatment.
COAST-V and COAST-W were 52-week, phase 3, randomized controlled trials evaluating the efficacy and safety of ixekizumab in biologic disease-modifying antirheumatic drug (bDMARD)-naïve and tumor necrosis factor inhibitor (TNFi)-experienced patients with radiographic spondyloarthritis, respectively. Patients were treated with 80-mg ixekizumab either every 2 weeks or every 4 weeks. Patient-reported outcomes included Patient Global Disease Activity, Spinal Pain, stiffness as measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Questions 5 and 6, function as measured by the Bath Ankylosing Spondylitis Functional Index, fatigue as measured by the Fatigue Numeric Rating Scale and BASDAI question 1, Spinal Pain at Night, and sleep quality as measured by the Jenkins Sleep Evaluation Questionnaire. Mixed-effects models for repeated measures were used to analyze changes from baseline in patient-reported outcomes from weeks 1 to 16, and descriptive statistics were reported from weeks 20 to 52. Analysis of covariance with Scheffé's method was used for the ASAS response association analyses.
This study assessed 341 bDMARD-naïve and 316 TNFi-experienced patients in the placebo-controlled blinded treatment dosing period (weeks 1-16) as well as 329 bDMARD-naïve and 281 TNFi-experienced patients in the dose double-blind extended treatment period (weeks 20-52). bDMARD-naïve or TNFi-experienced patients treated with ixekizumab every 2 weeks and every 4 weeks reported improvements in patient global disease activity, spinal pain, function, stiffness, fatigue, spinal pain at night, and sleep quality through week 52. Greater correlations with improvements in all response domains were seen when comparing ASAS40 responders to ASAS20 non-responders (p < 0.001), with up to 10.5-fold greater improvements observed in ASAS40 responses compared with ASAS20 non-responders. Function and fatigue demonstrated the highest values.
Ixekizumab-treated bDMARD-naïve and TNFi-experienced patients with radiographic axial spondyloarthritis achieving ASAS40 reported sustained and consistent improvement in all ASAS response domains and other patient-reported outcomes though week 52, with spinal pain, function, and stiffness as major drivers of the response.
NCT02696785 and NCT02696798 , March 2, 2016.
本分析评估了接受司库奇尤单抗治疗的放射学中轴型脊柱关节炎（r-axSpA）患者在国际脊柱关节炎协会（ASAS）治疗反应领域的改善情况以及治疗1年时其他患者报告的结局。
COAST-V和COAST-W是为期52周的3期随机对照试验，分别评估司库奇尤单抗在未使用过生物改善病情抗风湿药（bDMARD）和曾使用过肿瘤坏死因子抑制剂（TNFi）的放射学脊柱关节炎患者中的疗效和安全性。患者每2周或每4周接受80mg司库奇尤单抗治疗。患者报告的结局包括患者整体疾病活动度、脊柱疼痛、用巴斯强直性脊柱炎疾病活动指数（BASDAI）问题5和6测量的僵硬程度、用巴斯强直性脊柱炎功能指数测量的功能、用疲劳数字评定量表和BASDAI问题1测量的疲劳、夜间脊柱疼痛以及用詹金斯睡眠评估问卷测量的睡眠质量。采用重复测量的混合效应模型分析第1至16周患者报告结局相对于基线的变化，并报告第20至52周的描述性统计数据。采用协方差分析和谢费方法进行ASAS反应关联分析。
本研究评估了341例未使用过bDMARD和316例曾使用过TNFi的患者在安慰剂对照的盲法治疗给药期（第1至16周），以及329例未使用过bDMARD和281例曾使用过TNFi的患者在剂量双盲延长治疗期（第20至52周）。每2周和每4周接受司库奇尤单抗治疗的未使用过bDMARD或曾使用过TNFi的患者报告，至第52周时患者整体疾病活动度、脊柱疼痛、功能、僵硬程度、疲劳、夜间脊柱疼痛和睡眠质量均有改善。将ASAS40反应者与ASAS20无反应者进行比较时，在所有反应领域的改善方面观察到更大的相关性（p<0.001），与ASAS20无反应者相比，ASAS40反应的改善高达10.5倍。功能和疲劳的改善最为显著。
接受司库奇尤单抗治疗的未使用过bDMARD和曾使用过TNFi的放射学中轴型脊柱关节炎患者达到ASAS40标准，至第52周时在所有ASAS反应领域和其他患者报告的结局方面均有持续且一致的改善，脊柱疼痛、功能和僵硬程度为反应的主要驱动因素。
NCT02696785和NCT02696798，2016年3月2日。
