Wei James Cheng-Chung, Kim Tae-Hwan, Kishimoto Mitsumasa, Ogusu Naoki, Jeong Haeyoun, Kobayashi Shigeto
Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan.
Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Ann Rheum Dis. 2021 Aug;80(8):1014-1021. doi: 10.1136/annrheumdis-2020-219406. Epub 2021 Apr 7.
To investigate the efficacy and safety of brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with axial spondyloarthritis (axSpA).
In a multicentre, placebo-controlled phase 3 study (NCT02985983) conducted at 48 sites across Japan, Korea and Taiwan, patients with axSpA were randomised 1:1 to receive subcutaneous brodalumab 210 mg (n=80) or placebo (n=79) at baseline, weeks 1 and 2 and every 2 weeks thereafter, during the 16-week double-blind period. The primary endpoint was the proportion of patients with Assessment of SpondyloArthritis International Society (ASAS) 40 response at week 16. Secondary endpoints included the proportion of patients with ASAS 20 response and change in Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP) at week 16 and safety.
ASAS 40 response rate (n/N; 95% CI) was 43.8% (35/80; 32.7, 55.3) with brodalumab vs 24.1% (19/79; 15.1, 35.0) with placebo (rate difference, 19.7% (5.3, 34.1); p=0.018 by stratified Cochran-Mantel-Haenszel test). ASAS 20 response rate (n/N; 95% CI) was 67.5% (54/80; 56.1, 77.6) vs 41.8% (33/79; 30.8, 53.4) and least squares mean change (95% CI) from baseline (brodalumab, 2.660; placebo, 2.716) in ASDAS-CRP was -1.127 (-1.322, -0.931) with brodalumab vs -0.672 (-0.872, -0.473) with placebo at week 16. Treatment-emergent adverse events were reported in 44 (55%) and 45 (57%) patients in the brodalumab and placebo groups, respectively.
Brodalumab demonstrated a significant improvement at week 16 in patients with active axSpA. Safety of brodalumab was consistent with that reported in previous global/Japanese psoriasis studies.
研究全人源抗白细胞介素-17受体A单克隆抗体布罗达单抗治疗中轴型脊柱关节炎（axSpA）患者的疗效和安全性。
在日本、韩国和台湾地区48个地点开展的一项多中心、安慰剂对照3期研究（NCT02985983）中，axSpA患者按1:1随机分组，在基线、第1周和第2周以及之后每2周接受皮下注射布罗达单抗210mg（n = 80）或安慰剂（n = 79），为期16周的双盲期。主要终点是第16周达到国际脊柱关节炎评估协会（ASAS）40反应的患者比例。次要终点包括第16周达到ASAS 20反应的患者比例、使用C反应蛋白的强直性脊柱炎疾病活动评分（ASDAS-CRP）的变化以及安全性。
布罗达单抗组的ASAS 40反应率（n/N；95%CI）为43.8%（35/80；32.7，55.3），安慰剂组为24.1%（19/79；15.1，35.0）（率差为19.7%（5.3，34.）；分层Cochran-Mantel-Haenszel检验p = 0.018）。布罗达单抗组的ASAS 20反应率（n/N；95%CI）为67.5%（54/80；56.1，77.6），安慰剂组为41.8%（33/79；30.8，53.4），第16周时布罗达单抗组ASDAS-CRP较基线的最小二乘均值变化（95%CI）为-1.127（-1.322，-0.931），安慰剂组为-0.672（-0.872，-0.473）。布罗达单抗组和安慰剂组分别有44例（55%）和45例（57%）患者报告了治疗中出现的不良事件。
布罗达单抗在第16周时使活动性axSpA患者有显著改善。布罗达单抗的安全性与先前全球/日本银屑病研究报告的一致。
