University of Alberta, Edmonton, Canada.
UCB Pharma, Monheim am Rhein, Germany.
Arthritis Res Ther. 2021 Oct 29;23(1):274. doi: 10.1186/s13075-021-02650-4.
Identification of predictive clinical factors of long-term treatment response may contribute to improved management of non-radiographic axSpA (nr-axSpA) patients. This analysis aims to identify whether any baseline characteristics or Week 12 clinical outcomes in nr-axSpA patients with elevated C-reactive protein (CRP) and/or sacroiliitis on magnetic resonance imaging (MRI) enrolled in the C-axSpAnd study are predictive of achieving clinical response after 1 year of certolizumab pegol (CZP).
C-axSpAnd (NCT02552212) was a phase 3, multicentre study, including a 52-Week double-blind, placebo-controlled period. Enrolled patients were randomised to CZP 200 mg Q2W or placebo. Predictors of Week 12 (CZP group only) and Week 52 clinical response were identified using a multivariate stepwise logistic regression analysis. Response variables included Ankylosing Spondylitis Disease Activity Score major improvement (ASDAS-MI), Assessment of SpondyloArthritis International Society 40% response (ASAS40), Bath Ankylosing Spondylitis Disease Activity Index 50% response (BASDAI50) and ASDAS inactive disease (ASDAS-ID). Predictive factors assessed included demographic and baseline characteristics and clinical outcomes at Week 12. A p-value <0.05 was required for forward selection into the model and p ≥0.1 for backward elimination. Missing data or values collected after switching to open-label treatment were accounted for using non-responder imputation. Sensitivity analyses accounted for patients with changes in non-biologic background medication.
Of 317 enrolled patients, 159 and 158 were randomised to CZP and placebo, respectively. Younger age and male sex were identified as predictors of Week 12 response across all assessed efficacy outcomes in CZP-treated patients. Consistent predictors of Week 52 response, measured by ASDAS-MI, ASAS40 and BASDAI50, included human leukocyte antigen (HLA)-B27 positivity and sacroiliitis on MRI at baseline. MRI positivity was also predictive of achieving ASDAS-ID at Week 52. Sensitivity analyses were generally consistent with the primary analysis. In placebo-treated patients, no meaningful predictors of Week 52 response were identified.
In this 52-Week, placebo-controlled study in nr-axSpA patients with elevated CRP and/or active sacroiliitis on MRI at baseline, MRI sacroiliitis and HLA-B27 positivity, but not elevated CRP or responses at Week 12, were predictive of long-term clinical response to CZP. Findings may support rheumatologists to identify patients suitable for TNFi treatment.
ClinicalTrials.gov, NCT02552212 . Registered on 15 September 2015.
识别长期治疗反应的预测性临床因素可能有助于改善非放射性 axSpA（nr-axSpA）患者的管理。本分析旨在确定 C-axSpAnd 研究中基线时 CRP 升高和/或 MRI 显示存在中轴型脊柱关节炎（axSpA）骶髂关节炎的 nr-axSpA 患者中，任何基线特征或第 12 周临床结局是否可预测接受培塞利珠单抗（CZP）治疗 1 年后的临床缓解。
C-axSpAnd（NCT02552212）是一项为期 52 周的、多中心的 3 期研究，包括 52 周的双盲、安慰剂对照期。纳入的患者被随机分配至 CZP 200mg Q2W 或安慰剂组。使用多变量逐步逻辑回归分析确定第 12 周（仅 CZP 组）和第 52 周临床缓解的预测因子。缓解变量包括强直性脊柱炎疾病活动评分（ASDAS）主要改善（ASDAS-MI）、脊柱关节炎国际协会 40%反应（ASAS40）、Bath 强直性脊柱炎疾病活动指数 50%反应（BASDAI50）和 ASDAS 无疾病活动（ASDAS-ID）。评估的预测因素包括人口统计学和基线特征以及第 12 周的临床结局。正向选择进入模型的 p 值＜0.05，反向排除的 p 值≥0.1。对使用非生物背景药物治疗后发生改变的缺失数据或值，采用非应答者插补法处理。对改变非生物制剂背景药物治疗的患者进行敏感性分析。
在纳入的 317 例患者中，159 例和 158 例分别随机分配至 CZP 和安慰剂组。在接受 CZP 治疗的患者中，所有评估的疗效结局中，年龄较小和男性是第 12 周缓解的预测因素。在第 52 周时，通过 ASDAS-MI、ASAS40 和 BASDAI50 评估的缓解，基线时 HLA-B27 阳性和 MRI 显示存在中轴型脊柱关节炎（axSpA）骶髂关节炎是一致的预测因素。MRI 阳性也预测第 52 周时达到 ASDAS-ID。敏感性分析与主要分析基本一致。在安慰剂组中，未确定第 52 周缓解的有意义的预测因素。
在这项为期 52 周、安慰剂对照的研究中，基线时 CRP 升高和/或 MRI 显示存在中轴型脊柱关节炎（axSpA）骶髂关节炎的 nr-axSpA 患者中，MRI 骶髂关节炎和 HLA-B27 阳性，而不是 CRP 升高或第 12 周的反应，可预测接受培塞利珠单抗（CZP）治疗的长期临床缓解。这些发现可能有助于风湿病学家识别适合接受 TNFi 治疗的患者。
ClinicalTrials.gov，NCT02552212。2015 年 9 月 15 日注册。
