Thijs Vincent N, Cloud Geoffrey C, Gilchrist Nigel, Parsons Brooke, Tilvawala Forum, Ho Jan Kee, Ruthnam Lara, Stanislaus Vimal, Sprigg Nikola, Walker Marion, Bath Philip M, Churilov Leonid, Bernhardt Julie
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, Australia.
Florey Department of Neuroscience and Mental Health, University of Melbourne, Australia.
Neurology. 2025 Sep 23;105(6):e213981. doi: 10.1212/WNL.0000000000213981. Epub 2025 Sep 4.
Stroke is a leading cause of long-term disability. Etanercept, a competitive tumor necrosis factor-α inhibitor, has been proposed as a potential treatment for post-stroke impairments when given through a perispinal subcutaneous injection. We aimed to evaluate the safety and efficacy of perispinal etanercept in patients with chronic stroke.
The Perispinal Etanercept for Stroke Outcomes Study was a randomized, double-blind, placebo-controlled, parallel group trial conducted in 3 ambulatory research clinics in Australia and New Zealand. Eligible patients were aged between 18 and 70 years, had a stroke between 1 and 15 years before enrollment, had a modified Rankin Scale score of 2-5, and demonstrated reduced quality of life as assessed by the 36-Item Short Form Survey (SF-36). Patients were randomized in a 1:1 ratio. The primary outcome was the difference in the proportion of participants at day 28 with an improvement of 5 points or more on the SF-36v2 compared with baseline after a single injection of etanercept 25 mg or equivalent placebo. The primary safety outcome was the difference in the proportion over 28 days of serious adverse events after a single injection of etanercept 25 mg or equivalent placebo. The primary outcome and safety were analyzed in the intention-to-treat population. Participants were followed up 56 days after the first injection of perispinal etanercept.
Recruitment ceased early because of lack of continued funding. We screened 147 participants, of whom 126 were enrolled and randomized (63 etanercept: 63 placebo; 48 [38%] female, median (interquartile range) age 54.5 (45.0-60.0) years, median time since stroke 3 years). The primary outcome of improvement occurred in 33 of 63 participants (53%) in the etanercept arm and 36 of 63 participants (58%) in the placebo arm (adjusted odds ratio 0.82, 95% CI 0.40-1.67, standardized risk difference -5%, 95% CI -22% to 13%). The proportion of serious adverse events was similar in both treatment arms.
Perispinal etanercept was safe, but we found no evidence of improvement in quality of life and other efficacy outcomes compared with placebo.
The trial was registered at anzctr.org.au (ACTRN12620001011976) on October 7, 2020. Patients were enrolled between November 4, 2020, and September 1, 2023.
This study provides Class I evidence that in patients with imaging-confirmed ischemic or hemorrhagic stroke, perispinal etanercept (25 mg) injection does not improve the patients' quality of life 28 days after injection.
中风是导致长期残疾的主要原因。依那西普是一种竞争性肿瘤坏死因子-α抑制剂，有人提出通过脊柱旁皮下注射给予依那西普可能是治疗中风后损伤的一种方法。我们旨在评估脊柱旁注射依那西普对慢性中风患者的安全性和疗效。
脊柱旁注射依那西普治疗中风结局研究是一项在澳大利亚和新西兰的3个门诊研究诊所进行的随机、双盲、安慰剂对照、平行组试验。符合条件的患者年龄在18至70岁之间，在入组前1至15年发生过中风，改良Rankin量表评分为2 - 5分，并且通过36项简短调查问卷（SF - 36）评估显示生活质量下降。患者按1:1比例随机分组。主要结局是单次注射25 mg依那西普或等效安慰剂后第28天，SF - 36v2评分较基线提高5分或更多的参与者比例的差异。主要安全性结局是单次注射25 mg依那西普或等效安慰剂后28天内严重不良事件比例的差异。在意向性治疗人群中分析主要结局和安全性。在首次脊柱旁注射依那西普后56天对参与者进行随访。
由于缺乏持续资金，招募提前终止。我们筛选了147名参与者，其中126名被纳入并随机分组（63名依那西普组：63名安慰剂组；48名[38%]为女性，年龄中位数（四分位间距）为54.5（45.0 - 60.0）岁，中风后中位时间为3年）。依那西普组63名参与者中有33名（53%）出现改善这一主要结局，安慰剂组63名参与者中有36名（58%）出现改善（调整后的优势比为0.82，95%置信区间为0.40 - 1.67，标准化风险差异为 - 5%，95%置信区间为 - 22%至13%）。两个治疗组的严重不良事件比例相似。
脊柱旁注射依那西普是安全的，但与安慰剂相比，我们没有发现生活质量和其他疗效结局得到改善的证据。
该试验于2020年10月7日在anzctr.org.au（ACTRN12620001011976）注册。患者于2020年11月4日至2023年9月1日入组。
本研究提供了I类证据，即在影像学确诊的缺血性或出血性中风患者中，脊柱旁注射依那西普（25 mg）在注射后28天并不能改善患者的生活质量。
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