Eculizumab improves fatigue in refractory generalized myasthenia gravis

Henning Andersen,Jing Jing Wang,James F Howard,Fanny O’Brien,Kaushik Patra,Renato Mantegazza

doi:10.1007/s11136-019-02148-2

Abstract

PurposeTo evaluate the effect of eculizumab on perceived fatigue in patients with anti-acetylcholine receptor antibody-positive, refractory, generalized myasthenia gravis (MG) using the Quality of Life in Neurological Disorders (Neuro-QOL) Fatigue subscale, and to evaluate correlations between improvements in Neuro-QOL Fatigue and other clinical endpoints.MethodsNeuro-QOL Fatigue, MG Activities of Daily Living (MG-ADL), Quantitative MG (QMG), and the 15-item MG Quality of Life (MG-QOL15) scales were administered during the phase 3, randomized, placebo-controlled REGAIN study (eculizumab, n = 62; placebo, n = 63) and subsequent open-label extension (OLE). Data were analyzed using repeated-measures models. Correlations between changes in Neuro-QOL Fatigue and in MG-ADL, QMG, and MG-QOL15 scores were determined at REGAIN week 26.ResultsAt REGAIN week 26, eculizumab-treated patients showed significantly greater improvements in Neuro-QOL Fatigue scores than placebo-treated patients (consistent with improvements in MG-ADL, QMG, and MG-QOL15 scores previously reported in REGAIN). Improvements with eculizumab were sustained through OLE week 52. Correlations between Neuro-QOL Fatigue and MG-QOL15, MG-ADL, and QMG scores were strong for eculizumab-treated patients at REGAIN week 26, and strong, moderate, and weak, respectively, for placebo-treated patients.ConclusionsCompared with placebo, eculizumab was associated with improvements in perceived fatigue that strongly correlated with improvements in MG-specific outcome measures.Trial ID Registration: NCT01997229, NCT02301624.

Highlights

Patients with anti-acetylcholine receptor antibody-positive (AChR+), refractory, generalized myasthenia gravis experience muscle weakness, which is associated with complement-mediated damage at the neuromuscular junction [1, 2]
The current analysis investigated the effect of eculizumab versus placebo on fatigue in patients with AChR+ refractory generalized myasthenia gravis (gMG), and assessed the relationship between fatigue and myasthenia gravis (MG)-specific measures
Eculizumab was associated with greater improvements in fatigue than placebo

Summary

Introduction

Patients with anti-acetylcholine receptor antibody-positive (AChR+), refractory, generalized myasthenia gravis (gMG) experience muscle weakness, which is associated with complement-mediated damage at the neuromuscular junction [1, 2]. Validated MG-specific assessments used to measure disease severity and response to intervention include the patient-reported MG Activities of Daily Living (MG-ADL) and 15-item MG Quality of Life (MG-QOL15) scales, and the physician-completed Quantitative MG (QMG) assessment of muscle strength [8,9,10]. None of these evaluate the impact of fatigue in gMG. The Neuro-QOL Fatigue subscale comprises a 19-item, patient self-assessment of fatigue that encompasses ‘sensations ranging from tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that decrease one’s capacity for physical, functional, social, and mental activities’ [15]. A short form Neuro-QOL Fatigue subscale is available; this was recently validated in patients with MG [7]

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