A Longitudinal Study of the Neurologic Safety of Acute Baclofen Use After Spinal Cord Injury
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.
Keywordsspinal cord injury baclofen anti-spasticity drug safety patient-oriented research
Dr. Cragg is supported by the Society in Science—Branco Weiss Postdoctoral Fellowship and the Michael Smith Foundation for Health Research (MSFHR). Dr. Kramer is supported by a Scholar Award from the MSFHR and Rick Hansen Institute, as well as the Canadian Institutes of Health Research, ERA-NET NEURON, Wings for Life, and the International Foundation for Research in Paraplegia (IRP). Dr. Jutzeler is supported by the IRP and is a Craig H. Nielsen Foundation postdoctoral fellow. Ms. Warner is supported by the University of British Columbia Four Year Fellowship.
Required Author Forms
Disclosure forms provided by the authors are available with the online version of this article.
JJC was responsible for the design and conceptualization of the study, data analyses, and drafting the manuscript. BT was responsible for data cleaning, data analyses, and drafting the manuscript. CRJ, FMW, and NC were responsible for interpretation of data and revising the manuscript for intellectual content. FG was responsible for primary data collection, interpretation of data, and revising the manuscript for intellectual content. JLK was responsible for study concept/design, interpretation of data, and revising the manuscript for intellectual content.
Compliance with Ethical Standards
Approval for this study (secondary analysis) was received by an institutional ethical standards committee on human experimentation at the University of British Columbia.
All authors report no disclosures.
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