Myasthenia Gravis

Myasthenia gravis (MG) is a neuromuscular disease in which autoantibodies attack various proteins .¹ As a consequence, function of the neuromuscular junction is compromised, and the transmission of nerve impulses is affected. Patients with MG experience muscle weakness and fatigue, which increase with exertion. The disease may affect only certain muscles, such as those of the eyes, or it may be generalized and also affect muscles of the face and limbs, interfering with eating, drinking, speaking, and mobility.¹

Need for Guidelines in the Management of Myasthenia Gravis

The management of MG relies on immunosuppressive and immunomodulatory treatments; however, these are variable, and no standard of care for MG has been accepted.² A few large randomized controlled trials have been conducted, but the results have not provided all the information needed to establish effective, individualized treatment.² Therefore, consensus guidelines gathered from experts in the field have been developed to assist the MG care team in managing the disease.

Establishing International Consensus Guidance for the Management of Myasthenia Gravis

In 2013, the Myasthenia Gravis Foundation of America established an international task force comprising 15 experts in the management of MG. The task force focused on preparing formal, consensus-based guidelines for the management of MG. Definitions were developed for goals of treatment, minimal manifestations, remission, ocular MG, impending crisis, crisis, and refractory MG. The guidance statements were published in 2016 and covered topics ranging from the administration of intravenous immunoglobulin (IVIg) and plasma exchange (PLEX) to the management of myasthenic crisis.³

Recently, the consensus-based guidance developed in 2016 was updated according to the latest evidence in the literature. The guidelines were revised by an international panel of MG experts; new recommendations were added, and some of the previous statements were revised.⁴ The latest recommendations extend or add to the earlier consensus guidelines.

Recommendations for the Management of Myasthenia Gravis

Guidelines for the management of MG focus on the following: symptomatic and immunosuppressive treatment, use of IVIg and PLEX, management of impending and manifest myasthenic crisis, thymectomy, juvenile MG, MG with anti-muscle-specific tyrosine kinase (anti-MuSK) antibodies, and management of MG during pregnancy.^3,4 Several drugs that should not be administered, or administered cautiously, to patients with MG are listed within the updated consensus guidelines. These include antibiotics such aminoglycosides and fluoroquinolones, beta-blockers, chloroquine, and corticosteroids.⁴

For symptomatic MG, pyridostigmine is recommended as the initial treatment in most cases. When pyridostigmine is not effective, corticosteroids or immunosuppressive therapy should be used. Nonsteroidal immunosuppressive drugs should be used if corticosteroids are not an option. These include azathioprine, cyclosporine, mycophenolate mofetil, methotrexate, and tacrolimus.³ Refractory MG may be addressed with IVIg and PLEX, cyclophosphamide, or rituximab; IVIg and PLEX are ideally used as short-term treatments in patients who have severe respiratory insufficiency or dysphagia, or who are about to undergo surgery.³ Young children with juvenile MG and ocular symptoms can be initially treated with pyridostigmine.³ Patients with ophthalmoparesis or ptosis and functionally limiting symptoms should be treated with immunosuppressive agents.⁴

Rituximab is a therapeutic option for patients with anti-MuSK antibody-positive MG that does not respond to initial treatment with immunotherapy; it is also an option for patients who cannot tolerate immunosuppressive agents.⁴ Methotrexate is recommended as an alternative steroid-sparing treatment. Eculizumab should be considered for patients who have severe, generalized anti-acetylcholine receptor (anti-AChR) antibody-positive MG that is refractory to other treatments.⁴

Patients in myasthenic crisis should be hospitalized to undergo respiratory monitoring and the administration of IVIg and PLEX as short-term treatment, together with simultaneous corticosteroid or immunosuppressive therapy. The consensus experts suggest that PLEX is more effective and works more rapidly than IVIg.³

Thymectomy should be considered for patients aged 18 to 50 years with stable, anti-AChR-positive MG early in the disease course to improve clinical outcomes. This approach appears to reduce the need for immunotherapy and decrease the number of exacerbations requiring hospitalization.⁴ 

Pregnant patients with MG should receive oral pyridostigmine. Cholinesterase inhibitors should be avoided because they may induce uterine contractions. If immunosuppressive therapy is needed, prednisone should be the first option.³

Treatment with immune checkpoint inhibitors (ICIs) may increase the risk for immune-mediated neurologic illness in patients with MG. ICIs are not absolutely contraindicated if a patient’s MG is under control and monitored clinically.⁴ If the MG is exacerbated during ICI treatment, the administration of high doses of corticosteroids together with PLEX or IVIg may be necessary.⁴

References

1. Myasthenia gravis. National Organization for Rare Disorders (NORD). Accessed February 24, 2022

2. Sanders DB, Wolfe GI, Narayanaswami P. Developing treatment guidelines for myasthenia gravis. Ann N Y Acad Sci. 2018;1412(1):95-101. doi:10.1111/nyas.13537

3. Sanders DB, Wolfe GI, Benatar M, et al. International consensus guidance for management of myasthenia gravis: executive summary. Neurology. 2016;87(4):419-425. doi:10.1212/WNL.0000000000002790

4. Narayanaswami P, Sanders DB, Wolfe G, et al. International consensus guidance for management of myasthenia gravis: 2020 update. Neurology. 2021;;96(3):114-122. doi:10.1212/WNL.0000000000011124

Reviewed by Kyle Habet, MD, on 2/25/2022.

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Diana Diez Gaspar, PharmD, PhD

Diana earned her PhD and PharmD with distinction in the field of Medicinal and Pharmaceutical Chemistry at the Universidade do Porto. She is an accomplished oncology scientist with 10+ years of experience in developing and managing R&D projects and research staff directed to the development of small proteins fit for medical use.