The American Academy of Neurology (AAN) recently published a practice advisory on the use of etanercept for post-stroke disability, citing insufficient evidence to support or refute its efficacy or safety in the improvement of post-stroke disability.
The AAN Guideline Development, Dissemination, and Implementation Subcommittee (GDDI) were asked by members of the AAN for guidance on the use of etanercept for post-stroke disability. Based on animal studies, attenuation of inflammatory response from tumor-necrosis factor mediated microglial activation may affect outcomes by reducing secondary damage in the ischemic penumbra, prompting a review of the available data.
The AAN GDDI performed a literature search and identified 33 articles, of which 2 non-masked retrospective trials with a total of 620 patients met inclusion criteria. Patients were on average 65.8 years old and 42 months post-stroke; no standardized measure of disability was used. All patients were treated with perispinal injections of etanercept 25mg. Outcomes were measured immediately post-treatment at 1 week and 3 weeks using 14 pre-specified efficacy measures. Patients were reported to have improved outcomes in almost all measures and time points, including immediately post treatment. No safety or tolerability data were reported.
Because of the open label, retrospective design and numerous endpoint analyses, the GDDI determined that the relevant studies were highly susceptible to bias. The report of immediate improvement was also suspected to be related to placebo effect and not biologically plausible. At a cost of $440 for a 25 mg vial of etanercept and no safety data, the GDDI were not enthusiastic about endorsing the use of etanercept for post-stroke disability.
“Given the limitations of the efficacy of the evidence and the potential for serious adverse events, we judge the risk-to-benefit tradeoffs of etanercept for post-stroke disability to be unfavorable,” they wrote.