Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark.
Ann Rheum Dis. 2018 Sep;77(9):1295-1302. doi: 10.1136/annrheumdis-2018-213328. Epub 2018 Jun 26.
To evaluate the efficacy and safety of risankizumab, a humanised monoclonal antibody targeting the p19 subunit of interleukin-23 (IL-23), in patients with active ankylosing spondylitis (AS).
A total of 159 patients with biological-naïve AS, with active disease (Bath Ankylosing Spondylitis Disease Activity Index score of ≥4), were randomised (1:1:1:1) to risankizumab (18 mg single dose, 90 mg or 180 mg at day 1 and weeks 8, 16 and 24) or placebo over a 24-week blinded period. The primary outcome was a 40% improvement in Assessment in Spondylo Arthritis International Society (ASAS40) at week 12. Safety was assessed in patients who received at least one dose of study drug.
At week 12, ASAS40 response rates were 25.5%, 20.5% and 15.0% in the 18 mg, 90 mg and 180 mg risankizumab groups, respectively, compared with 17.5% in the placebo group. The estimated difference in proportion between the 180 mg risankizumab and placebo groups (primary endpoint) was -2.5% (95% CI -21.8 to 17.0; p=0.42). Rates of adverse events were similar in all treatment groups.
Treatment with risankizumab did not meet the study primary endpoint and showed no evidence of clinically meaningful improvements compared with placebo in patients with active AS, suggesting that IL-23 may not be a relevant driver of disease pathogenesis and symptoms in AS.
NCT02047110; Pre-results.
评估靶向白细胞介素 23（IL-23）p19 亚单位的人源化单克隆抗体 risankizumab 在活动性强直性脊柱炎（AS）患者中的疗效和安全性。
共有 159 名生物初治、疾病活动（Bath 强直性脊柱炎疾病活动指数评分≥4）的 AS 患者被随机（1:1:1:1）分配至 risankizumab（18mg 单次剂量，第 1 天和第 8、16、24 周给予 90mg 或 180mg）或安慰剂组，进行为期 24 周的双盲治疗。主要终点为第 12 周时评估强直性脊柱炎国际协会（ASAS40）改善 40%。至少接受一剂研究药物的患者被评估安全性。
第 12 周时，18mg、90mg 和 180mg risankizumab 组的 ASAS40 应答率分别为 25.5%、20.5%和 15.0%，安慰剂组为 17.5%。180mg risankizumab 与安慰剂组（主要终点）之间比例的估计差异为-2.5%（95%CI-21.8 至 17.0；p=0.42）。所有治疗组的不良反应发生率相似。
与安慰剂相比， risankizumab 治疗未达到研究主要终点，且未显示出在活动性 AS 患者中具有临床意义的改善，这表明 IL-23 可能不是 AS 疾病发病机制和症状的相关驱动因素。
NCT02047110；预注册结果。
