Division of Arthritis & Rheumatic Diseases, Oregon Health & Science University, Portland, OR, USA.
Department of Rheumatology, Leiden University Medical Centre, Leiden, Netherlands.
Lancet. 2020 Jan 4;395(10217):53-64. doi: 10.1016/S0140-6736(19)32971-X. Epub 2019 Dec 5.
Ixekizumab, a high-affinity interleukin-17A (IL-17A) monoclonal antibody, has previously shown efficacy in radiographic axial spondyloarthritis (also known as ankylosing spondylitis). We aimed to evaluate the efficacy and safety of ixekizumab, an IL-17 inhibitor, in non-radiographic axial spondyloarthritis. Here, we report the primary results of COAST-X.
COAST-X was a 52-week, randomised, double-blind, placebo-controlled, parallel-group study done at 107 sites in 15 countries in Europe, Asia, North America, and South America. Eligible participants were adults (aged ≥18 years) with active axial spondyloarthritis without definite radiographic sacroiliitis (non-radiographic axial spondyloarthritis), objective signs of inflammation (via MRI or C-reactive protein), and an inadequate response or intolerance to non-steroidal anti-inflammatory drugs (NSAIDs). Patients were randomly assigned (1:1:1) to receive subcutaneous 80 mg ixekizumab every 4 weeks (Q4W) or every 2 weeks (Q2W), or placebo. Changing background medications or switching to open-label ixekizumab Q2W, or both, was allowed after week 16 at investigator discretion. Primary endpoints were Assessment of SpondyloArthritis international Society-40 (ASAS40) response (defined as an improvement of 40% or more and an absolute improvement from baseline of 2 units or more [range 0-10] in at least three of the four domains [patient global, spinal pain, function, and inflammation] without any worsening in the remaining one domain) at weeks 16 and 52. Patients who switched to open-label ixekizumab were imputed as non-responders in logistic regression analysis. This trial is registered with ClinicalTrials.gov, number NCT02757352.
Between Aug 2, 2016, and Jan 29, 2018, 303 patients were enrolled (105 to placebo, 96 to ixekizumab Q4W, and 102 to ixekizumab Q2W). Both primary endpoints were met: ASAS40 at week 16 (ixekizumab Q4W: 34 [35%] of 96, p=0·0094 vs placebo; ixekizumab Q2W: 41 [40%] of 102, p=0·0016; placebo: 20 [19%] of 105) and ASAS40 at week 52 (ixekizumab Q4W: 29 [30%] of 96, p=0·0045; ixekizumab Q2W: 32 [31%] of 102, p=0·0037; placebo: 14 [13%] of 105). 60 (57%) of 104 patients in the placebo group, 63 (66%) of 96 in the ixekizumab Q4W group, and 79 (77%) of 102 in the ixekizumab Q2W group had at least one treatment-emergent adverse event. The most common treatment-emergent adverse events in the ixekizumab groups were nasopharyngitis and injection site reaction. Of the treatment-emergent adverse events of special interest, there was one case of serious infection in the ixekizumab Q4W group. The frequency of serious adverse events was low (four [1%] of 302) and similar across the three groups. There were no malignancies or deaths. No new safety signals were identified.
Ixekizumab was superior to placebo for improving signs and symptoms in patients with non-radiographic axial spondyloarthritis at weeks 16 and 52. Reports of adverse events were similar to those of previous ixekizumab studies. Ixekizumab offers a potential therapeutic option for patients with non-radiographic axial spondyloarthritis who had an inadequate response or were intolerant to NSAID therapy.
Eli Lilly and Company.
依奇珠单抗是一种高亲和力的白细胞介素-17A（IL-17A）单克隆抗体，先前已显示在放射学轴向脊柱关节炎（也称为强直性脊柱炎）方面的疗效。我们旨在评估 IL-17 抑制剂依奇珠单抗在非放射学轴向脊柱关节炎中的疗效和安全性。在这里，我们报告了 COAST-X 的主要结果。
COAST-X 是一项为期 52 周的随机、双盲、安慰剂对照、平行组研究，在 15 个国家/地区的 107 个地点进行，包括欧洲、亚洲、北美和南美。符合条件的参与者为年龄≥18 岁的成年人，患有活动期轴向脊柱关节炎，无明确的放射学骶髂关节炎（非放射学轴向脊柱关节炎），存在客观炎症迹象（通过 MRI 或 C 反应蛋白），并且对非甾体抗炎药（NSAIDs）反应不足或不耐受。患者被随机分配（1:1:1）接受皮下注射 80mg 依奇珠单抗每 4 周（Q4W）、每 2 周（Q2W）或安慰剂。在第 16 周后，根据研究者的判断，可以允许改变背景药物或转换为开放标签的依奇珠单抗 Q2W，或两者兼用。主要终点是在第 16 周和第 52 周时评估脊柱关节炎国际协会 40 项（ASAS40）应答（定义为至少四个领域中的三个领域[患者整体、脊柱疼痛、功能和炎症]改善 40%或更多，并且与基线相比绝对改善 2 个单位或更多[范围 0-10]，而其余一个领域没有任何恶化）。在逻辑回归分析中，转换为开放标签依奇珠单抗的患者被假定为无应答者。这项试验在 ClinicalTrials.gov 上注册，编号为 NCT02757352。
在 2016 年 8 月 2 日至 2018 年 1 月 29 日期间，共纳入 303 名患者（105 名接受安慰剂，96 名接受依奇珠单抗 Q4W，102 名接受依奇珠单抗 Q2W）。两个主要终点均达到：第 16 周时的 ASAS40（依奇珠单抗 Q4W：96 名中的 34 名[35%]，p=0.0094 对比安慰剂；依奇珠单抗 Q2W：102 名中的 41 名[40%]，p=0.0016；安慰剂：105 名中的 20 名[19%]）和第 52 周时的 ASAS40（依奇珠单抗 Q4W：96 名中的 29 名[30%]，p=0.0045；依奇珠单抗 Q2W：102 名中的 32 名[31%]，p=0.0037；安慰剂：105 名中的 14 名[13%]）。安慰剂组中 104 名患者中的 60 名（57%）、依奇珠单抗 Q4W 组中 96 名患者中的 63 名（66%）和依奇珠单抗 Q2W 组中 102 名患者中的 79 名（77%）发生了至少一次治疗后出现的不良事件。依奇珠单抗组中最常见的治疗后出现的不良事件是鼻咽炎和注射部位反应。在特别关注的治疗后出现的不良事件中，依奇珠单抗 Q4W 组中有一例严重感染。严重不良事件的频率较低（302 名中的 4 名[1%]），且在三组中相似。没有发生恶性肿瘤或死亡事件。没有发现新的安全信号。
与安慰剂相比，依奇珠单抗在第 16 周和第 52 周时改善了非放射学轴向脊柱关节炎患者的体征和症状。不良事件报告与之前的依奇珠单抗研究相似。依奇珠单抗为对 NSAIDs 治疗反应不足或不耐受的非放射学轴向脊柱关节炎患者提供了一种潜在的治疗选择。
礼来公司。
