Kong Ning, Hu Jiankang, Liu Dongzhou, Li Jingyang, Wu Huaxiang, Sun Lingyun, Lie Dai, Tan Chunyu, Li Zhijun, Xiao Zhengyu, Huang Cibo, Xu Jian, Yan Yan, Li Hongying, Zou Hejian
Department of Rheumatology, Huashan Hospital Affiliated to Fudan University, No. 12 Urumqi Middle Road, Jing'an District, Shanghai, 2000400, China.
Department of Rheumatology, Pingxiang People's Hospital, Pingxiang, Jiangxi, China.
Rheumatol Ther. 2025 May 9. doi: 10.1007/s40744-025-00765-7.
Ixekizumab, an interleukin 17A inhibitor, improved the Assessment of SpondyloArthritis international Society 40 (ASAS40) response rates irrespective of baseline inflammation in international populations with radiographic axial spondyloarthritis (r-axSpA). We investigated the association of baseline inflammation (measured by serum C-reactive protein [CRP] levels) with ixekizumab efficacy in Chinese patients with r-axSpA.
This was a subgroup analysis of a Chinese phase 3 study. Adults with r-axSpA who were biologic-naïve, or tumor necrosis factor inhibitor-experienced with baseline CRP > 5 mg/l, were randomized (1:1) to receive ixekizumab 80 mg every 4 weeks (IXEQ4W) or placebo, for 16 weeks. The following endpoints were analyzed by normal (≤ 5 mg/l) or elevated (> 5 mg/l) baseline CRP levels: ASAS40; Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50); Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1; ASDAS clinically important improvement (CII; change from baseline ≥ 1.1); ASDAS major improvement (MI; change from baseline ≥ 2.0 or achievement of lowest possible score); Bath Ankylosing Spondylitis Metrology Index (BASMI) linear score; Bath Ankylosing Spondylitis Functional Index (BASFI); Short Form-36 Physical Component Score (SF-36 PCS).
A total of 147 patients were randomized. At week 16, the ASAS40 response rate was greater with IXEQ4W versus placebo in the normal (50.0% vs. 15.0%; p < 0.05) and elevated (29.5% vs. 5.7%; p < 0.01) CRP subgroups. Significant improvements in BASDAI50 response rate, ASDAS < 2.1, and ASDAS CII with IXEQ4W versus placebo were observed in both subgroups (normal CRP: p < 0.05, p < 0.01, and p < 0.05, respectively; elevated CRP: p < 0.01, p < 0.001, and p < 0.001, respectively); IXEQ4W significantly improved ASDAS MI in the elevated CRP subgroup (p < 0.001). IXEQ4W significantly improved linear BASMI and BASFI scores in the normal CRP subgroup (p < 0.001 and p < 0.01, respectively), while SF-36 PCS improved in both subgroups (both p < 0.05).
Ixekizumab showed efficacy in Chinese patients with r-axSpA, irrespective of baseline CRP levels, consistent with results in international populations with r-axSpA.
ClinicalTrials.gov identifier, NCT04285229.
司库奇尤单抗是一种白细胞介素17A抑制剂，在患有放射学轴向性脊柱关节炎（r-axSpA）的国际人群中，无论基线炎症情况如何，均可提高脊柱关节炎国际协会40（ASAS40）反应率。我们研究了基线炎症（通过血清C反应蛋白[CRP]水平测量）与司库奇尤单抗对中国r-axSpA患者疗效之间的关联。
这是一项中国3期研究的亚组分析。将初治的或曾使用肿瘤坏死因子抑制剂且基线CRP>5 mg/l的r-axSpA成年患者按1:1随机分组，接受每4周一次的80 mg司库奇尤单抗（IXEQ4W）或安慰剂治疗，为期16周。根据基线CRP水平正常（≤5 mg/l）或升高（>5 mg/l）分析以下终点指标：ASAS40；巴斯强直性脊柱炎疾病活动指数50（BASDAI50）；强直性脊柱炎疾病活动评分（ASDAS）<2.1；ASDAS临床重要改善（CII；相对于基线变化≥1.1）；ASDAS重大改善（MI；相对于基线变化≥2.0或达到最低可能分数）；巴斯强直性脊柱炎测量指数（BASMI）线性评分；巴斯强直性脊柱炎功能指数（BASFI）；简明健康状况调查量表身体成分评分（SF-36 PCS）。
共147例患者被随机分组。在第16周时，正常CRP亚组（50.0%对15.0%；p<0.05）和升高CRP亚组（29.5%对5.7%；p<0.01）中，接受IXEQ4W治疗的患者ASAS40反应率高于接受安慰剂治疗的患者。在两个亚组中均观察到，与安慰剂相比，IXEQ4W治疗的患者BASDAI50反应率、ASDAS<2.1及ASDAS CII均有显著改善（正常CRP亚组：分别为p=0.05、p<0.01和p<0.05；升高CRP亚组：分别为p<0.01、p<0.001和p<0.001）；在升高CRP亚组中，IXEQ4W显著改善了ASDAS MI（p<0.001）。在正常CRP亚组中，IXEQ4W显著改善了BASMI线性评分和BASFI评分（分别为p<0.001和p<0.01），而两个亚组的SF-36 PCS均有改善（均为p<0.05）。
司库奇尤单抗对中国r-axSpA患者显示出疗效且不受基线CRP水平影响，这与国际r-axSpA人群的结果一致。
ClinicalTrials.gov标识符，NCT04285229。
