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Ixekizumab for patients with non-radiographic axial spondyloarthritis (COAST-X): a randomised, placebo-controlled trial.

Ixekizumab治疗非影像学轴向脊柱关节炎 (COAST-X) 患者: 一项随机、安慰剂对照试验。

  • 影响因子:0
  • DOI:10.1016/S0140-6736(19)32971-X
  • 作者列表:"Deodhar A","van der Heijde D","Gensler LS","Kim TH","Maksymowych WP","Østergaard M","Poddubnyy D","Marzo-Ortega H","Bessette L","Tomita T","Leung A","Hojnik M","Gallo G","Li X","Adams D","Carlier H","Sieper J","COAST-X Study Group.
  • 发表时间:2020-01-04
Abstract

BACKGROUND: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. METHODS: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. FINDINGS: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. INTERPRETATION: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. FUNDING:Eli Lilly and Company.

摘要

背景: Ixekizumab是一种高亲和力的interleukin-17A (IL-17A) 单克隆抗体,以前在放射学中轴脊柱关节炎 (也称为强直性脊柱炎) 中显示出疗效。我们旨在评价IL-17 抑制剂ixekizumab治疗非影像学中轴型脊柱关节炎的疗效和安全性。在此,我们报道了COAST-X的主要结果。 方法: COAST-X是一项为期 52 周、随机、双盲、安慰剂对照、平行组研究,在欧洲、亚洲、北美 15 个国家的 107 个地点进行,和南美洲。符合条件的参与者是患有活动性中轴脊柱关节炎的成年人 (年龄 ≥ 18 岁),没有明确的影像学骶髂关节炎 (非影像学中轴脊柱关节炎),炎症的客观体征 (通过MRI或C反应蛋白),以及对非甾体抗炎药 (NSAIDs) 反应不足或不耐受。患者被随机分配 (1:1:1) 接受皮下 80 mg ixekizumab每 4 周 (Q4W) 或每 2 周 (Q2W),或安慰剂。根据研究者的判断,16 周后允许改变背景药物或改用开放标签ixekizumab Q2W,或两者兼而有之。主要终点是脊柱关节炎国际Society-40 (ASAS40) 的评估。应答 (定义为在四个领域中的至少三个领域中,从基线 2 个单位或更多 [范围 0-10] 的 40% 或更多的改善和绝对改善 [患者全球,脊柱疼痛、功能和炎症]在 16 周和 52 周时,其余一个域没有任何恶化)。在logistic回归分析中,改用开放标签ixekizumab的患者被定为非应答者。该试验在ClinicalTrials.gov注册,编号为nct02757352。 结果: 在 2016 年 8 月 2 日至 20 18 年 1 月 29 日期间,入组了 303 例患者 (安慰剂组 105 例,ixekizumab Q4W组 96 例,ixekizumab Q2W组 102 例)。满足两个主要终点: 16 周时ASAS40 (ixekizumab Q4W: 34 [35%] of 96,p = 0 · 0094 vs安慰剂; ixekizumab Q2W: 41 [40%] of 102,p = 0 · 0016; 安慰剂: 20 [19%] 的 105) 和ASAS40 在 52 周 (ixekizumab Q4W: 29 [30%]96,p = 0 · 0045; ixekizumab Q2W: 32 [31%] of 102,p = 0 · 0037; 安慰剂: 14 [13%] of 105)。安慰剂组 57% 例患者中 60 例 (104),ixekizumab Q4W组 96 例患者中 63 例 (66%),79 例 (77%) 在ixekizumab Q2W组中,102 的患者至少有一个治疗中出现的不良事件。Ixekizumab组最常见的治疗突发不良事件为鼻咽炎和注射部位反应。在特别感兴趣的治疗中出现的不良事件中,ixekizumab Q4W组有 1 例严重感染。严重不良事件的频率较低 (1% 中的 4 例 [302]),三组相似。没有恶性肿瘤或死亡。未发现新的安全信号。 解释: Ixekizumab在 16 周和 52 周时改善非影像学中轴型脊柱关节炎患者的体征和症状优于安慰剂。不良事件报告与以往ixekizumab研究的报告相似。Ixekizumab为对NSAID治疗反应不足或不耐受的非影像学中轴型脊柱关节炎患者提供了潜在的治疗选择。 资助: 礼来和公司。

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