Braun Jürgen, Deodhar Atul, Landewé Robert, Baraliakos Xenofon, Miceli-Richard Corinne, Sieper Joachim, Quebe-Fehling Erhard, Martin Ruvie, Porter Brian, Gandhi Kunal K, van der Heijde Désirée
Rheumazentrum Ruhrgebiet, Ruhr-University Bochum, Herne, Germany.
Oregon Health & Science University, Portland, Oregon, USA.
RMD Open. 2018 Nov 21;4(2):e000749. doi: 10.1136/rmdopen-2018-000749. eCollection 2018.
To evaluate the magnitude of response to secukinumab treatment over 3 years in patients with ankylosing spondylitis (AS) grouped by baseline C-reactive protein (CRP) levels in a pooled study of two pivotal phase III studies: MEASURE 1 (NCT01358175) and MEASURE 2 (NCT01649375).
This post hoc analysis pooled data from all patients with available baseline CRP in the two studies who received subcutaneous secukinumab 150 mg (approved dose; N=197) or placebo (N=195). Assessed efficacy endpoints included Assessments of SpondyloArthritis international Society (ASAS)20/40, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI50, AS Disease Activity Score inactive disease and ASAS partial remission among patients grouped by baseline CRP based on central laboratory cut-off <5 mg/L (normal) or ≥5 mg/L (elevated) and a cut-off <10 mg/L or ≥10 mg/L.
At baseline, 36.5% (143/392) patients had normal and 63.5% (249/392) had elevated CRP. At week 16, ASAS20/40 response rates were higher for secukinumab versus placebo in normal (56.9%/34.7% vs 28.2%/7.0%; p<0.01/p<0.001) and in elevated (63.2%/42.4% vs 29.0%/15.3%; both p<0.0001) CRP groups. Improvement was reported for all outcomes (p<0.05) in both groups, except for ASAS partial remission in the normal CRP group, where a numerical difference 12.5% vs 2.8%, p=0.07) was observed. Similar trends of improvement were observed in the <10 and ≥10 mg/L groups across all efficacy outcomes at week 16. Treatment responses to secukinumab in all CRP groups further improved over 156 weeks.
Secukinumab 150 mg demonstrated rapid and sustained efficacy in patients with AS irrespective of baseline CRP, with greater magnitude of response in patients with more elevated CRP.
在两项关键的III期研究（MEASURE 1，NCT01358175；MEASURE 2，NCT01649375）的汇总研究中，按基线C反应蛋白（CRP）水平对强直性脊柱炎（AS）患者进行分组，评估司库奇尤单抗治疗3年的反应程度。
这项事后分析汇总了两项研究中所有有可用基线CRP数据、接受皮下注射司库奇尤单抗150mg（批准剂量；N = 197）或安慰剂（N = 195）的患者的数据。评估的疗效终点包括国际脊柱关节炎协会（ASAS）20/40反应、巴斯强直性脊柱炎疾病活动指数（BASDAI）、BASDAI50、AS疾病活动评分（非活动疾病）以及ASAS部分缓解，患者按基于中心实验室临界值<5mg/L（正常）或≥5mg/L（升高）以及<10mg/L或≥10mg/L的基线CRP进行分组。
在基线时，36.5%（143/392）的患者CRP正常，63.5%（249/392）的患者CRP升高。在第16周时，正常CRP组（56.9%/34.7%对28.2%/7.0%；p<0.01/p<0.001）和升高CRP组（63.2%/42.4%对29.0%/15.3%；均p<0.0001）中，司库奇尤单抗的ASAS20/40反应率高于安慰剂。两组所有结局均有改善（p<0.05），除了正常CRP组的ASAS部分缓解，观察到数值差异（12.5%对2.8%，p = 0.07）。在第16周时，<10mg/L和≥10mg/L组在所有疗效结局方面均观察到类似的改善趋势。所有CRP组对司库奇尤单抗的治疗反应在156周内进一步改善。
无论基线CRP如何，150mg司库奇尤单抗在AS患者中均显示出快速且持续的疗效，CRP升高程度较高的患者反应程度更大。
