目的:评估布罗达鲁单抗的长期疗效和安全性,完全人抗白细胞介素17受体A单克隆抗体,中轴脊柱关节炎(axSpA)患者。
方法:在该多中心的16周双盲期间接受皮下brodalumab210mg的患者,在日本进行的第三阶段研究,在为期52周的开放标签扩展中,韩国和台湾继续如此,而接受安慰剂的患者在第16周改用brodalumab210mg。评价疗效(脊柱炎国际协会[ASAS]40和ASAS20反应率;使用C-反应蛋白[ASDAS-CRP]的强直性脊柱炎疾病活动评分相对于基线的变化)和安全性。
结果:总体而言,145名患者(brodalumab,n=77;安慰剂,n=68)在开放标签扩展期间接受了brodalumab。ASAS40反应率(95%置信区间[CI])为56.3%(44.7%,67.3%)和57.4%(44.1%,70.0%)在brodalumab和安慰剂组中实现,分别,第68周两个治疗组在第68周达到的ASAS20反应率(95%CI)相似(brodalumab,71.3%[60.0%,80.8%];安慰剂,78.7%[66.3%,88.1%])。第68周时ASDAS-CRP的最小二乘平均变化(95%CI)提示临床上重要的改善(变化,≥1.1)在两个治疗组(brodalumab,-1.528[-1.737,-1.319];安慰剂,-1.586[-1.815,-1.357])。治疗引起的不良事件(TEAE)和药物相关TEAE的暴露校正事件发生率(每100名患者年)分别为255.9和147.9;鼻咽炎(35.6)和上呼吸道感染(14.7)是最常见的TEAE。
结论:Brodalumab在axSpA患者68周内表现出持续疗效和一致的安全性。
背景:ClinicalTrials.gov,https://clinicaltrials.gov,NCT02985983。
To evaluate the long-term efficacy and safety of
brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, in patients with axial spondyloarthritis (axSpA).
Patients receiving subcutaneous
brodalumab 210 mg during the 16-week double-blind period of this multicentre, phase 3 study conducted across Japan, Korea and Taiwan continued the same during the 52-week open-label extension, whereas patients receiving placebo switched to brodalumab 210 mg at week 16. Efficacy [Assessment of SpondyloArthritis International Society (ASAS) 40 and ASAS 20 response rates; change from baseline in AS Disease Activity Score using CRP (ASDAS-CRP)] and safety were evaluated.
Overall, 145 patients (
brodalumab, n = 77; placebo, n = 68) received
brodalumab during the open-label extension. ASAS 40 response rates (95% CI) of 56.3% (44.7%, 67.3%) and 57.4% (44.1%, 70.0%) were achieved in the brodalumab and placebo groups, respectively, at week 68. ASAS 20 response rates (95% CI) achieved at week 68 in both treatment groups were similar [
brodalumab, 71.3% (60.0%, 80.8%); placebo, 78.7% (66.3%, 88.1%)]. The least squares mean change (95% CI) in ASDAS-CRP at week 68 suggested a clinically important improvement (change, ≥1.1) in both treatment groups [brodalumab, -1.528 (-1.737, -1.319); placebo, -1.586 (-1.815, -1.357)]. The exposure-adjusted event rates (per 100 patient-years) for treatment-emergent adverse events (TEAEs) and drug-related TEAEs were 255.9 and 147.9, respectively; nasopharyngitis (35.6) and upper respiratory tract infection (14.7) were the most common TEAEs.
Brodalumab demonstrated sustained efficacy and a consistent safety profile in patients with axSpA over 68 weeks.
ClinicalTrials.gov, https://clinicaltrials.gov, NCT02985983.