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

Abstract

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); most patients achieved a ‘none’ or ‘mild’ rating for QMG evaluations; all patients reduced their daily prednisone dose; and eight 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.

Practical Management for Use of Eculizumab in the Treatment of Severe, Refractory, Non-Thymomatous, AChR + Generalized Myasthenia Gravis: A Systematic Review

“…This retrospective review also demonstrated similar safety data, with 10 mild adverse events reported. 44 …”

“…This retrospective review also demonstrated similar safety data, with 10 mild adverse events reported. 44 A post-marketing interim analysis of 40 patients with treatment-refractory AChR+ gMG treated with eculizumab in Japan between 2017 and 2019 similarly showed reductions in mean MG-ADL and QMG scores, as well as reductions in IVIg treatments. This study also demonstrated safety data at par with the phase II, phase III, and OLE trials, with 16 adverse events reported.…”

Safety and outcomes of eculizumab for acetylcholine receptor‐positive generalized myasthenia gravis in clinical practice

“…We observed improvements in both patient-reported (MG-ADL) and physician assessed (MG-MMT) outcomes as in prior studies. 1,2,[7][8][9] Notably, a clinically significant decrease occurred in MG-ADL from baseline to 1-mo follow-up and was sustained.…”

Clinical Efficacy and Safety of Eculizumab for Treating Myasthenia Gravis

“…In general, eculizumab was well tolerated, and a change in the eculizumab treatment schedule due to the occurrence of side effects was not necessary. If the patient experiences mild symptoms, they are generally subjected to treatment with symptomatic drugs such as acetaminophen or paracetamol ( 51 ). Overall, patients discontinued treatment owing to the development of serious side effects such as MG exacerbation and myasthenic crisis.…”