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Tolerability and efficacy of erythropoietin (EPO) treatment in traumatic spinal cord injury: a preliminary randomized comparative trial vs. methylprednisolone (MP)

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Abstract

The only available treatment of traumatic spinal cord injury (TSCI) is high-dose methylprednisolone (MP) administered acutely after injury. However, as the efficacy of MP is controversial, we assessed the superiority of erythropoietin (EPO) versus MP in improving clinical outcome of acute TSCI. Patients aged 18 to 65 years after C5–T12 injury, and grade A or B of the ASIA Impairment Scale (AIS), admitted within 8 h, hemodynamically stable, were randomized to MP according to the NASCIS III protocol or EPO iv (500 UI/kg, repeated at 24 and 48 h). Patients were assessed by an investigator blind to treatment assignment at baseline and at day 3, 7, 14, 30, 60 and 90. Primary end point: number of responders (reduction of at least one AIS grade). Secondary end points: treatment safety and the effects of drugs on a number of disability measures. Frequentistic and post hoc Bayesian analyses were performed. Eight patients were randomized to MP and 11 to EPO. Three patients (27.3 %) on EPO and no patients on MP reached the primary end point (p = 0.17). No significant differences were found for the other disability measures. No adverse events or serious adverse events were reported in both groups. The Bayesian analysis detected a 91.8 % chance of achieving higher success rates on the primary end point with EPO in the intention-to-treat population with a 95 % chance the difference between EPO and MP falling in the range (−0.10, 0.51) and a median value of 0.2. The results of Bayesian analysis favored the experimental treatment.

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Acknowledgments

The study was funded by the Italian Drug Agency (Agenzia Italiana del Farmaco), contract number FARM6Y35XMI.

Conflict of interest

Ettore Beghi has received personal fees for board membership by VIROPHARMA and GSK; has received funding for travel and speaker honoraria from UCB-Pharma and GSK, for educational presentations from GSK; has received Grants for research activities from the Italian Drug Agency, Italian Ministry of Health, EISAI and the American ALS Association. Elisabetta Pupillo has received funding from the American ALS Association and Italian Ministry of Health for data management and data monitoring of an observational study protocol. She is receiving funding from Italian Drug Agency (AIFA) for data monitoring and study management of randomized clinical trial. Paolo Messina has received funding from Sanofi-Aventis, EISAI, Lombardy Region, and the American ALS Association for the data analysis and data management of RCT and observational study protocol. Paola Carignano, Davide Dalla Costa, Franco Faccioli, Alfredo Gorio, Cristina Pagliacci and Tiziana Redaelli: nothing to disclose.

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Authors and Affiliations

  1. Spinal Unit, Niguarda Ca’ Granda Hospital, Milan, Italy

    Davide Dalla Costa & Tiziana Redaelli

  2. Laboratory of Neurological Disorders, IRCCS, Mario Negri Institute for Pharmacological Research, Via Giuseppe La Masa, 19, 20156, Milan, Italy

    Ettore Beghi, Elisabetta Pupillo & Paolo Messina

  3. C.T.O./C.R.F./M. Adelaide Hospital, Turin, Italy

    Paola Carignano

  4. Spinal Unit of Umbria, Silvestrini Hospital, Perugia, Italy

    Cristina Pagliacci

  5. Spinal Neurosurgery, Civile Hospital, Verona, Italy

    Franco Faccioli

  6. Pharmacological Laboratories, Departments of Medicine, Surgery and Odontoiatry, Faculty of Medicine, Polo H. San Paolo, Milan, Italy

    Alfredo Gorio

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  1. Davide Dalla Costa
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Correspondence to Ettore Beghi.

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Costa, D.D., Beghi, E., Carignano, P. et al. Tolerability and efficacy of erythropoietin (EPO) treatment in traumatic spinal cord injury: a preliminary randomized comparative trial vs. methylprednisolone (MP). Neurol Sci 36, 1567–1574 (2015). https://doi.org/10.1007/s10072-015-2182-5

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  • DOI: https://doi.org/10.1007/s10072-015-2182-5

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