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

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.

Human recombinant erythropoietin improves motor function in rats with spinal cord compression myelopathy

“…In this trial, the effect of EPO treatment was compared with high-dose methylprednisolone treatment. EPO had higher efficacy and fewer side effects than methylprednisolone, indicating a therapeutic effect for acute SCI patients [25].…”

“…Those papers reported its effect of neuroprotection, angiogenesis, and anti-apoptosis in the brain and spinal cord [18, 24]. Recently, recombinant human EPO (rhEPO) was preliminarily used in a randomized clinical trial of acute SCI, and results indicated the possibility of treating acute SCI with EPO [25].…”

Peripheral nerve injury and myelination: Potential therapeutic strategies

“…In addition to the fundamental myeloprotective role of EPO, these findings also demonstrated an anti‐oxidative effect of EPO at the site of nerve injury which is consistent with the direct role of EPO against oxidative stress (Maiese et al, ). Given EPO’s widespread and frequent use to treat anemia in humans and its favorable side effect profile (Itri, ; Straus, ), early clinical trials have already begun investigating EPO’s therapeutic potential treating human peripheral nerve trauma associated with joint replacement surgery (Bernstein et al, ; Costa et al, ). It is also noteworthy that clinical use of EPO is not without problems, in particular the route of administration and the potent side effect profile.…”

Regulation of Inflammatory Cytokines for Spinal Cord Injury Repair Through Local Delivery of Therapeutic Agents

“…Ten paraparetic patients with malignant extradural spinal cord compression (MESCC) received 1500 IU kg −1 EPO by chemotherapy infusion pump over 30 min and showed improved motor function and shorter recovery time, including functional class and ambulation 244. Additionally, Costa et al found that intravenous administration of EPO resulted in a meaningful clinical improvement in ASIA Impairment Scale scores compared with MP treatment 245. Meanwhile, the combination of EPO and MP has been confirmed in clinical trials to be beneficial for SCI treatment 246.…”