Retrospective Analysis of Eculizumab in Patients with Acetylcholine Receptor Antibody-Negative Myasthenia Gravis: A Case Series

Abstract

Background: The role of the complement cascade in acetylcholine receptor antibody-negative (AChR-) myasthenia gravis (MG) is unclear.

Objective: To assess the efficacy and tolerability of eculizumab (terminal complement inhibitor) in patients with AChR-MG.

Methods: Retrospective chart review of data from six patients treated for 12 months with eculizumab for treatment-refractory, AChR-(by radioimmunoassay) generalized MG (gMG). The eculizumab dose was 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, and qualitative physical assessments based on selected items of the Quantitative Myasthenia Gravis evaluation (ptosis, double vision, eye closure, duration of ability to stretch out limbs).

Results: All patients were female (mean age, 50.8 years). In the 12 months before eculizumab initiation, all measures were relatively stable. After its initiation, clinically meaningful reductions (≥2 points) in total MG-ADL scores were observed before or at 5 months and were maintained to Month 12 in all patients; mean (standard deviation [SD]) scores were 11.3 (0.9) and 5.0 (0.9), respectively. There was also a reduction in the mean (SD) number of exacerbations per patient, from 2.8 (1.2) to 0.3 (0.5) in the 12 months before and after eculizumab initiation, respectively. Physical assessment ratings were improved in all patients. Adverse events were reported in four patients, but all were mild and none were treatment-related.

Conclusions: This small retrospective analysis provides preliminary evidence for the efficacy of eculizumab in treatment-refractory gMG that was AChR-according to radioimmunoassay. Larger, more robust studies are warranted to evaluate this further.

Keywords: ACh receptors; Myasthenia gravis; activities of daily living; complement inactivating agents; corticosteroids; neuromuscular junction.

Fig. 1

MG-ADL total scores before and during 12 months’ treatment with eculizumab. MG-ADL, Myasthenia Gravis–Activities of Daily Living.

Fig. 2

Number of exacerbations in the 12 months before and after starting eculizumab.

Fig. 3

Changes in generalized myasthenia gravis medication after starting eculizumab. ^a12 months after starting eculizumab, three patients had their daily prednisone doses reduced from 50 mg to 10 mg, 15 mg and 20 mg, respectively, two patients had their dose reduced from 40 mg to 10 mg (the sixth patient also had her dose reduced, from 30 mg to 10 mg); ^bIn the three patients who continued pyridostigmine treatment after eculizumab initiation, two had their dose reduced from 60 mg TID to 30 mg TID and one had her dose reduced from 60 mg QID to 60 mg TID; ^cFurther details of doses can be found in Table 1. IVIG, intravenous immunoglobulin; PLEX, plasma exchange; QID, four times daily; TID, three times daily.

Fig. 4

Changes in physical assessments during treatment with eculizumab. Physical parameters were based on a qualitative assessment of selected items from the QMG evaluation and classified as mild, moderate or severe [23]. QMG, Quantitative Myasthenia Gravis.

Fig. 5

SBCT scores in the 12 months before and after eculizumab administration. SBCT, single breath count test.