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Randomized Controlled Trial
. 2021 Jul;8(7):1398-1407.
doi: 10.1002/acn3.51376. Epub 2021 May 27.

Long-term efficacy of eculizumab in refractory generalized myasthenia gravis: responder analyses

James F Howard Jr  1 , Chafic Karam  2 , Marcus Yountz  3 , Fanny L O'Brien  3 , Tahseen Mozaffar  4 ; REGAIN Study Group
Affiliations
Randomized Controlled Trial

Long-term efficacy of eculizumab in refractory generalized myasthenia gravis: responder analyses

James F Howard Jr et al. Ann Clin Transl Neurol. 2021 Jul.

Abstract

Objective: Generalized myasthenia gravis (gMG) is an autoimmune disease that causes disabling weakness via damage to the neuromuscular junction. In most patients, the disease is mediated by autoantibodies to the acetylcholine receptor, which activate the complement cascade. Our objective was to analyze response profiles in adult patients with anti-acetylcholine receptor antibody-positive refractory gMG treated with eculizumab-a terminal complement inhibitor-in the REGAIN study or its open-label extension (OLE).

Methods: We retrospectively analyzed Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores recorded during REGAIN and its OLE. Early/late responses were defined as improvement in MG-ADL score (≥3 points) or QMG score (≥5 points) at ≤12 or >12 weeks, respectively, after eculizumab initiation.

Results: The analysis included 98 patients. By Week 12 and conclusion of the OLE, MG-ADL response had been achieved at some point by 67.3% and 84.7% of patients, respectively, and QMG response by 56.1% and 71.4%, respectively. Response was observed over multiple consecutive assessments for most patients. At Week 130, the least-squares mean percentage changes (95% CI) from baseline in MG-ADL score were -61.9% (-69.9%, -53.9%) and -47.5% (-59.0%, -36.0%) in early and late MG-ADL responders, respectively; the least-squares mean percentage changes from baseline in QMG score were -40.8% (-48.3%, -33.4%) and -55.5% (-68.4%, -42.7%) in early and late QMG responders, respectively.

Interpretation: The findings suggest that, although most patients with refractory gMG will achieve clinical response by Week 12 of eculizumab treatment, first responses can be observed with longer-term treatment.

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Conflict of interest statement

J.F.H. Jr received research support from argenx SE, Alexion Pharmaceuticals, and UCB‐Ra; advisory‐board honoraria from Alexion Pharmaceuticals, argenx SE, UCB‐Ra, Regeneron Pharmaceuticals, and Viela Bio Inc; and owns stocks in Johnson & Johnson and Pfizer. C.K. has served on advisory boards or provided advisory input for Acceleron, Alexion, Alnylam, Akcea, argenx, Biogen, CSL, Sanofi Genzyme, and UCB‐Ra, and has received research grants from Acceleron, Alexion, Alnylam, Akcea, argenx, CSL, Sanofi Genzyme, and UCB‐Ra. M.Y. and F.L.O’B. are employed by and own stocks in Alexion Pharmaceuticals. T.M. has served on advisory boards for AbbVie, Alexion, argenx, Audentes Therapeutics, Momenta, Sanofi Genzyme, Sarepta, Spark Therapeutics, The Myositis Association, The Neuromuscular Disease Foundation, and UCB‐Ra. In relation to these activities, he has received travel subsidies and honoraria. He has also served on the speaker’s bureaus for Alexion and Sanofi Genzyme, and receives research funding from the Myositis Association, the Muscular Dystrophy Association, and the National Institutes for Health, and from the following sponsors: Acceleron, Alexion, argenx, Audentes Therapeutics, Momenta, Sanofi Genzyme, Spark Therapeutics, UCB‐Ra, and Valerion. He serves on a data safety monitoring board for Acceleron.

Figures

FIGURE 1
FIGURE 1
Efficacy of eculizumab (response analysis set). Percent change from baseline in (A) MG‐ADL total score and (B) QMG total score. Data are least‐squares mean ± 95% confidence interval estimates. MG‐ADL, Myasthenia Gravis‐Activities of Daily Living; QMG, Quantitative Myasthenia Gravis.
See this image and copyright information in PMC

References

    1. Hehir MK, Silvestri NJ. Generalized myasthenia gravis: classification, clinical presentation, natural history, and epidemiology. Neurol Clin 2018;36:253–260. - PubMed
    1. Silvestri NJ, Wolfe GI. Treatment‐refractory myasthenia gravis. J Clin Neuromuscul Dis 2014;15:167–178. - PubMed
    1. Meriggioli MN, Sanders DB. Muscle autoantibodies in myasthenia gravis: beyond diagnosis? Expert Rev Clin Immunol 2012;8:427–438. - PMC - PubMed
    1. Biesecker G, Gomez CM. Inhibition of acute passive transfer experimental autoimmune myasthenia gravis with Fab antibody to complement C6. J Immunol 1989;142:2654–2659. - PubMed
    1. Christadoss P. C5 gene influences the development of murine myasthenia gravis. J Immunol 1988;140:2589–2592. - PubMed

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