'Minimal symptom expression' in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab. J Neurol 2020 Jul;267(7):1991-2001
Date
03/20/2020Pubmed ID
32189108Pubmed Central ID
PMC7320935DOI
10.1007/s00415-020-09770-yScopus ID
2-s2.0-85085089028 (requires institutional sign-in at Scopus site) 30 CitationsAbstract
BACKGROUND: The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension.
METHODS: Attainment of 'minimal symptom expression' was evaluated using patient-reported outcome measures of gMG symptoms [MG activities of daily living scale (MG-ADL), 15-item MG quality of life questionnaire (MG-QOL15)] at the completion of REGAIN and during the open-label extension. 'Minimal symptom expression' was defined as MG-ADL total score of 0-1 or MG-QOL15 total score of 0-3.
RESULTS: At REGAIN week 26, more eculizumab-treated patients achieved 'minimal symptom expression' versus placebo [MG-ADL: 21.4% vs 1.7%; difference 19.8%; 95% confidence interval (CI) 8.5, 31.0; p = 0.0007; MG-QOL15: 16.1% vs 1.7%; difference 14.4%; 95% CI 4.3, 24.6; p = 0.0069]. During the open-label extension, the proportion of patients in the placebo/eculizumab group who achieved 'minimal symptom expression' increased after initiating eculizumab treatment and was sustained through 130 weeks of open-label eculizumab (MG-ADL: 1.7 to 27.8%; MG-QOL15: 1.7 to 19.4%). At extension study week 130, similar proportions of patients in the eculizumab/eculizumab and placebo/eculizumab groups achieved 'minimal symptom expression' (MG-ADL: 22.9% and 27.8%, respectively, p = 0.7861; MG-QOL15: 14.3% and 19.4%, respectively, p = 0.7531). The long-term tolerability of eculizumab was consistent with previous reports.
CONCLUSIONS: Patients with AChR+ refractory gMG who receive eculizumab can achieve sustained 'minimal symptom expression' based on patient-reported outcomes. 'Minimal symptom expression' may be a useful tool in measuring therapy effectiveness in gMG.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01997229, NCT02301624.
Author List
Vissing J, Jacob S, Fujita KP, O'Brien F, Howard JF, REGAIN study groupAuthor
Marek Cierny MD Adjunct Assistant Professor in the Neurology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Activities of Daily LivingAdult
Aged
Antibodies, Monoclonal, Humanized
Autoantibodies
Double-Blind Method
Female
Humans
Immunologic Factors
Male
Middle Aged
Myasthenia Gravis
Patient Reported Outcome Measures
Quality of Life
Receptors, Cholinergic