Clinical Experience with Eculizumab in Treatment-Refractory Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis

Background: Although established therapies are effective in most patients with generalized myasthenia gravis (gMG), some patients do not respond or they experience intolerable adverse events, highlighting the need for better tolerated, targeted therapies for treatment-refractory gMG. Objective: To describe real-world experience with eculizumab in patients with treatment-refractory acetylcholine receptor antibody-positive (AChR+) gMG. Methods: Retrospective chart review of 15 patients with treatment-refractory AChR+ gMG treated for 12 months with eculizumab (900 mg/week for 4 weeks then 1200 mg every 2 weeks). Outcome measures were Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores, number of exacerbations, single-breath count test (SBCT) score, medication changes, selected Quantitative Myasthenia Gravis (QMG) evaluations, and adverse events. Data collected at 3-monthly intervals for 12 months before and after eculizumab initiation were analyzed. Results: Clinically meaningful reductions in total MG-ADL scores were observed at 3 months following eculizumab initiation and maintained up to 12 months in all patients. After 12 months' eculizumab treatment, there was a significant reduction in the number of acute exacerbations; mean (SD) SBCT score improved from 28.13 (0.33) to 50.26 (2.86); all patients achieved a 'none' or 'mild' rating for QMG evaluations; all patients reduced their daily prednisone dose; and nine patients had discontinued pyridostigmine. At the end of treatment, intravenous immunoglobulin was discontinued in all six patients receiving this therapy at eculizumab initiation. Eculizumab was well tolerated. Conclusions: This real-world study demonstrated improvement in outcome measures and decreased concomitant drug requirement within 12 months of eculizumab initiation in patients with treatment-refractory AChR+ gMG.