Eculizumab in refractory generalized myasthenia gravis

Introduction: Myasthenia gravis is a human autoimmune disease. Current treatment options include cholinesterase inhibitors, thymectomy, corticosteroids, azathioprine, cyclosporine, tacrolimus, mycophenolate mofetil, cyclophosphamide, methotrexate, intravenous immunoglobulin, and plasmapheresis. Approximately 10% patients are refractory to these treatments and other options of treatment are rituximab and etanercept. Eculizumab is approved for the treatment of refractory generalized myasthenia gravis patients who are AChR antibody-positive. However, there are no alternatives to eculizumab approved by the regulatory agencies with the same indication. Clinical efficacy: Three clinical trials were carried out: a phase III study (Study ECU-MG-301), an extension study of Study ECU-MG-301 with preliminary results (Study ECU-MG-302) and another phase II study (Study C08-001). Therefore, the only EC in phase III (Study ECU-MG-301) was developed with defined results. It was a multicenter trial to evaluate the safety and efficacy of eculizumab for the treatment of patients with refractory generalized myasthenia gravis. A total of 170 patients were screened, of whom 44 did not meet the inclusion criteria. The remaining 126 patients were randomized, 63 patients in the eculizumab arm and 63 patients in the placebo arm. The mean (SD) change from baseline to week 26 in MG-ADL total score was greater in patients who received eculizumab (–4.7 [4.32]) than in patients who received placebo (–2.8 [3.07]) with p-value of 0.0698. Clinical safety: The most frequently reported serious adverse events were those related to infections (both in the placebo arm and eculizumab arm) and gastrointestinal disorders. Two deaths were reported in the total of the studies, one in ECU-MG-301 (eculizumab arm) possibly related to eculizumab and another in ECU-MG-302 (eculizumab / eculizumab arm) with causality difficult to establish. Economic study: According to Study ECU-MG-301, and the cost of treatment, for each point of the MG-ADL Tuestionnaire in weeN 26, the estimated additional cost is €147,109.9 (95% CI: €86,803.9-490,366.3). Therapeutic positioning: Eculizumab could be considered a more therapeutic option in patients with generalized myasthenia gravis, class II to IV according to MG)A and score ≥6 on the MG-ADL scale, refractory, with positive AChR, who do not respond or have intolerance to three or more immunosuppressants therapies. Patients should be evaluated periodically and those who do not show evidence of therapeutic benefit after 12 weeks should stop treatment