Advances in autoimmune myasthenia gravis management

ABSTRACT

Introduction: Myasthenia gravis (MG) is an autoimmune neuromuscular disorder with no cure and conventional treatments limited by significant adverse effects and variable benefit. In the last decade, therapeutic development has expanded based on improved understanding of autoimmunity and financial incentives for drug development in rare disease. Clinical subtypes exist based on age, gender, thymic pathology, autoantibody profile, and other poorly defined factors, such as genetics, complicate development of specific therapies.

Areas covered: Clinical presentation and pathology vary considerably among patients with some having weakness limited to the ocular muscles and others having profound generalized weakness leading to respiratory insufficiency. MG is an antibody-mediated disorder dependent on autoreactive B cells which require T-cell support. Treatments focus on elimination of circulating autoantibodies or inhibition of effector mechanisms by a broad spectrum of approaches from plasmapheresis to B-cell elimination to complement inhibition.

Expert commentary: Standard therapies and those under development are disease modifying and not curative. As a rare disease, clinical trials are challenged in patient recruitment. The great interest in development of treatments specific for MG is welcome, but decisions will need to be made to focus on those that offer significant benefits to patients.

KEYWORDS:

• Myasthenia gravis
• clinical trials
• mycophenolate
• tacrolimus
• prednisone
• eculizumab
• rituximab
• interleukins
• plasma cells
• acetylcholine receptor antibody
• muscle-specific kinase

Declaration of interest

HJ Kaminski is supported by Muscular Dystrophy Association (Grant No: 508,240), serves on the editorial board of Experimental Neurology, is co-editor of Neuromuscular Disorders in Clinical Practice and Myasthenia Gravis and Related Disorders. He has received monetary compensation for serving on data and safety monitoring committees for Novartis and NeuroNext. He consults for Alnylam, UCB Pharma, RA Pharmaceuticals, Momenta Therapeutics, and GT Biopharma. He has received research funding from the National Institutes of Health, the Myasthenia Gravis Foundation of Illinois, Akari Therapeutics, and the Neumann Professorship. He has patent US 8,961,981 issues. J Guptill receives research support from National Institute of Neurological Disorders and Stroke (K23NS085049; HHSN27100001), the Myasthenia Gravis Foundation of America, Ra Pharmaceuticals, Bioverativ and the Jose Antonio Grifols Lucas Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was supported by the Muscular Dystrophy Association (Grant No: 508240) and the National Institutes of Health (K23NS085049; HHSN27100001).