Fehlings, Michael GPedro, Karlo MAlvi, Mohammed AliBadhiwala, Jetan HAhn, HenryFarhadi, H FrancisShaffrey, Christopher INassr, AhmadMummaneni, PraveenArnold, Paul MJacobs, W BradleyRiew, K DanielKelly, MichaelBrodke, Darrel SVaccaro, Alexander RHilibrand, Alan SWilson, JasonHarrop, James SYoon, S TimKim, Kee DFourney, Daryl RSantaguida, CarloMassicotte, Eric MHuang, Peng2024-08-082024-08-082024-062574-38052574-3805https://hdl.handle.net/10161/31346<h4>Importance</h4>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.<h4>Objective</h4>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.<h4>Design, setting, and participants</h4>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.<h4>Intervention</h4>Riluzole (50 mg twice daily) or placebo for a total of 6 weeks, including 2 weeks prior to surgery and 4 weeks following surgery.<h4>Main outcomes and measures</h4>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).<h4>Results</h4>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).<h4>Conclusions and relevance</h4>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.Cervical VertebraeHumansSpinal Cord DiseasesRiluzoleNeuroprotective AgentsTreatment OutcomeDouble-Blind MethodAgedMiddle AgedFemaleMaleSpondylosisJournal article