Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
Division of Neurosurgery and Spine Program, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
JAMA Netw Open. 2024 Jun 3;7(6):e2415643. doi: 10.1001/jamanetworkopen.2024.15643.
IMPORTANCE: The modified Japanese Orthopaedic Association (mJOA) scale is the most common scale used to represent outcomes of degenerative cervical myelopathy (DCM); however, it lacks consideration for neck pain scores and neglects the multidimensional aspect of recovery after surgery. OBJECTIVE: To use a global statistical approach that incorporates assessments of multiple outcomes to reassess the efficacy of riluzole in patients undergoing spinal surgery for DCM. DESIGN, SETTING, AND PARTICIPANTS: This was a secondary analysis of prespecified secondary end points within the Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-PROTECT) trial, a multicenter, double-blind, phase 3 randomized clinical trial conducted from January 2012 to May 2017. Adult surgical patients with DCM with moderate to severe myelopathy (mJOA scale score of 8-14) were randomized to receive either riluzole or placebo. The present study was conducted from July to December 2023. INTERVENTION: Riluzole (50 mg twice daily) or placebo for a total of 6 weeks, including 2 weeks prior to surgery and 4 weeks following surgery. MAIN OUTCOMES AND MEASURES: The primary outcome measure was a difference in clinical improvement from baseline to 1-year follow-up, assessed using a global statistical test (GST). The 36-Item Short Form Health Survey Physical Component Score (SF-36 PCS), arm and neck pain numeric rating scale (NRS) scores, American Spinal Injury Association (ASIA) motor score, and Nurick grade were combined into a single summary statistic known as the global treatment effect (GTE). RESULTS: Overall, 290 patients (riluzole group, 141; placebo group, 149; mean [SD] age, 59 [10.1] years; 161 [56%] male) were included. Riluzole showed a significantly higher probability of global improvement compared with placebo at 1-year follow-up (GTE, 0.08; 95% CI, 0.00-0.16; P = .02). A similar favorable global response was seen at 35 days and 6 months (GTE for both, 0.07; 95% CI, -0.01 to 0.15; P = .04), although the results were not statistically significant. Riluzole-treated patients had at least a 54% likelihood of achieving better outcomes at 1 year compared with the placebo group. The ASIA motor score and neck and arm pain NRS combination at 1 year provided the best-fit parsimonious model for detecting a benefit of riluzole (GTE, 0.11; 95% CI, 0.02-0.16; P = .007). CONCLUSIONS AND RELEVANCE: In this secondary analysis of the CSM-PROTECT trial using a global outcome technique, riluzole was associated with improved clinical outcomes in patients with DCM. The GST offered probability-based results capable of representing diverse outcome scales and should be considered in future studies assessing spine surgery outcomes.
重要性:改良日本骨科协会(mJOA)量表是最常用于表示退行性颈椎脊髓病(DCM)结果的量表;然而,它没有考虑颈部疼痛评分,也忽略了手术后的多维恢复。
目的:使用一种综合评估多种结果的全球统计方法,重新评估利鲁唑在接受 DCM 脊柱手术的患者中的疗效。
设计、地点和参与者:这是 Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy(CSM-PROTECT)试验中预先指定的次要终点的二次分析,这是一项多中心、双盲、随机、3 期临床试验,于 2012 年 1 月至 2017 年 5 月进行。患有中度至重度脊髓病(mJOA 评分 8-14)的 DCM 手术患者被随机分为利鲁唑组或安慰剂组。本研究于 2023 年 7 月至 12 月进行。
干预:利鲁唑(50mg,每日两次)或安慰剂,共 6 周,包括手术前 2 周和手术后 4 周。
主要结果和测量:主要结局测量指标是从基线到 1 年随访的临床改善差异,使用全球统计检验(GST)评估。36 项简短健康调查身体成分评分(SF-36 PCS)、手臂和颈部疼痛数字评分量表(NRS)评分、美国脊髓损伤协会(ASIA)运动评分和 Nurick 分级结合成一个单一的综合统计量,称为全球治疗效果(GTE)。
结果:共有 290 名患者(利鲁唑组 141 名,安慰剂组 149 名;平均[标准差]年龄 59[10.1]岁;161[56%]为男性)纳入研究。与安慰剂相比,利鲁唑在 1 年随访时具有更高的全球改善概率(GTE,0.08;95%置信区间,0.00-0.16;P=0.02)。在 35 天和 6 个月时也观察到了类似的有利的全球反应(GTE 均为 0.07;95%置信区间,-0.01 至 0.15;P=0.04),尽管结果没有统计学意义。与安慰剂组相比,利鲁唑治疗的患者在 1 年内获得更好结局的可能性至少高出 54%。1 年时的 ASIA 运动评分和颈部及手臂疼痛 NRS 联合评分是检测利鲁唑疗效的最佳简约模型(GTE,0.11;95%置信区间,0.02-0.16;P=0.007)。
结论和相关性:在 CSM-PROTECT 试验的这项二次分析中,使用全球结局技术,利鲁唑与 DCM 患者的临床结局改善相关。GST 提供了基于概率的结果,能够代表多种结局量表,应在未来评估脊柱手术结局的研究中考虑使用。
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