Huashan Hospital affiliated to Fudan University, 12 Wulumuqi Zhong Rd, Shanghai, 200040, China.
Pingxiang People's Hospital, Pingxiang, Jiangxi Province, China.
BioDrugs. 2024 Jan;38(1):145-156. doi: 10.1007/s40259-023-00625-2. Epub 2023 Sep 22.
Ixekizumab, an interleukin-17A inhibitor, was efficacious and well tolerated for the treatment of active radiographic axial spondyloarthritis (r-axSpA) in international clinical studies. This phase III study aimed to determine the efficacy and safety of ixekizumab for treating Chinese patients with active r-axSpA.
Adults with active r-axSpA naïve to biologic disease-modifying antirheumatic drugs (bDMARDs), or with an inadequate response/intolerance to one tumor necrosis factor inhibitor, were randomized (1:1), double-blind, to receive ixekizumab 80 mg every 4 weeks (IXEQ4W; starting dose 160 mg), or placebo, for 16 weeks. Patients receiving placebo were then switched to IXEQ4W, and those receiving IXEQ4W continued, until week 52. The primary endpoint was the proportion of bDMARD-naïve patients achieving an Assessment of SpondyloArthritis International Society 40 (ASAS40) response at week 16.
In total, 147 patients were randomized to receive placebo (n = 73) or IXEQ4W (n = 74). At week 16, more bDMARD-naive patients achieved ASAS40 in the IXEQ4W group (n = 66; 40.9%) than the placebo group (n = 64, 7.8%; p < 0.001). In the overall study population, ASAS40 was also achieved by more patients in the IXEQ4W group (37.8%) than the placebo group (8.2%; p < 0.001) at week 16, with a significant difference observed as early as week 1. There were significant improvements in all key secondary endpoints at week 16 with IXEQ4W versus placebo. Efficacy was sustained at week 52 in patients who continued IXEQ4W and there were also clinical improvements from weeks 16 to 52 in patients switched to IXEQ4W. The safety profile of ixekizumab was consistent with that described previously. Infections and injection-site reactions were the most frequently reported events of special interest.
IXEQ4W was associated with rapid and significant improvements in the signs and symptoms of active r-axSpA in Chinese patients at week 16 that were sustained at week 52, with no new safety signals.
ClinicalTrials.gov identifier: NCT04285229.
依奇珠单抗是一种白介素-17A 抑制剂，在国际临床研究中，对于治疗活动性影像学轴性脊柱关节炎（r-axSpA）是有效的，且耐受性良好。这项 III 期研究旨在确定依奇珠单抗治疗中国活动性 r-axSpA 患者的疗效和安全性。
既往未接受生物改善病情抗风湿药（bDMARDs）治疗或对一种肿瘤坏死因子抑制剂应答不足/不耐受的活动性 r-axSpA 成年患者，按 1:1 比例、双盲，随机分配接受依奇珠单抗 80mg 每 4 周（IXEQ4W；起始剂量 160mg）或安慰剂治疗 16 周。接受安慰剂的患者随后转换为 IXEQ4W，而接受 IXEQ4W 的患者继续治疗，直到第 52 周。主要终点是在第 16 周时，bDMARD 初治患者中达到 ASAS40 应答的比例。
共有 147 例患者被随机分配接受安慰剂（n=73）或 IXEQ4W（n=74）。在第 16 周，IXEQ4W 组有更多的 bDMARD 初治患者（n=66；40.9%）达到 ASAS40，而安慰剂组（n=64，7.8%；p<0.001）。在整个研究人群中，IXEQ4W 组在第 16 周时也有更多的患者达到 ASAS40（37.8%），而安慰剂组（8.2%；p<0.001），并且早在第 1 周就观察到了显著差异。与安慰剂相比，IXEQ4W 在第 16 周时还显著改善了所有关键次要终点。在继续接受 IXEQ4W 治疗的患者中，第 52 周时疗效持续，在转换为 IXEQ4W 的患者中，从第 16 周到第 52 周也有临床改善。依奇珠单抗的安全性与先前描述的一致。感染和注射部位反应是最常报告的特殊关注事件。
IXEQ4W 在中国活动性 r-axSpA 患者中可在第 16 周迅速显著改善疾病的体征和症状，第 52 周时仍持续缓解，且无新的安全性信号。
ClinicalTrials.gov 标识符：NCT04285229。
