International Collaboration on Repair Discoveries (ICORD), University of British Columbia, 818 West 10th Avenue, Vancouver, British Columbia, V5Z 1M9, Canada.
School of Kinesiology, University of British Columbia, Vancouver, British Columbia, Canada.
Neurotherapeutics. 2019 Jul;16(3):858-867. doi: 10.1007/s13311-019-00713-8.
The objective of our study was to determine whether treatment with baclofen is neurologically safe with respect to exposure during recovery from spinal cord injury. We performed a secondary longitudinal analysis of a cohort of adult patients with traumatic acute spinal cord injury. Cumulative baclofen dose was computed over the first 4 weeks following injury from concomitant medication information from a completed clinical trial. The main outcome measure was neurologic status, which was assessed over 52 weeks with "marked recovery" defined as the conversion to higher sensory and motor function. To complete the drug safety profile, drug toxicity was assessed with assays from standard blood work. Multivariable Cox regression was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). Of the cohort (n = 651), 18% (n = 115) received baclofen within 4 weeks post injury. Baclofen use was associated with higher rates of marked neurologic recovery, even after adjustment for injury severity (HR = 2.1, 95% CI 1.5-3.0 for high dose vs none). Baclofen exposure was not associated with liver or renal side effects. The use of other medications indicated for spasticity was not associated with neurological outcomes. Overall, this longitudinal analysis provides level 3 evidence on the neurologic safety of baclofen and potential beneficial effects on recovery in the early days after acute traumatic spinal cord injury. The usefulness of concomitant medication files from completed clinical trials is highlighted. We also highlight the importance of incorporating logical patient questions and neurological outcomes into research addressing drug safety.
我们的研究目的是确定巴氯芬治疗在脊髓损伤恢复期间的暴露是否具有神经安全性。我们对一组成年创伤性急性脊髓损伤患者进行了队列的二次纵向分析。累积巴氯芬剂量是根据完成的临床试验中的伴随药物信息，从损伤后第 1 至 4 周计算得出的。主要结局指标是神经状态，通过“明显恢复”来评估，定义为向更高的感觉和运动功能的转变，持续 52 周。为了完成药物安全性概况，通过标准血液检查评估药物毒性。使用多变量 Cox 回归计算风险比 (HR) 和 95%置信区间 (CI)。在队列中（n=651），18%（n=115）在损伤后 4 周内接受了巴氯芬。即使在调整损伤严重程度后，巴氯芬的使用与更高的明显神经恢复率相关（高剂量与无剂量相比，HR=2.1，95%CI 为 1.5-3.0）。巴氯芬暴露与肝或肾副作用无关。其他用于痉挛的药物的使用与神经结局无关。总体而言，这项纵向分析提供了巴氯芬神经安全性的 3 级证据，并表明在急性创伤性脊髓损伤后早期对恢复有潜在的有益作用。突出了从完成的临床试验中利用伴随药物文件的重要性。我们还强调了将逻辑患者问题和神经结局纳入解决药物安全性的研究中的重要性。
