PAGE CONTENTS

Therapies

Acetylcholinesterase Inhibitors

Pyridostigmine (Mestinon) is an acetylcholinesterase inhibitor that is recommended for the initial management of most patients with myasthenia gravis (MG). The response to pyridostigmine is not uniform, and most patients with antibodies to muscle-specific kinase (MuSK) respond suboptimally. Patients in this group usually require treatment with corticosteroids and other immunosuppressive agents.¹ Pyridostigmine can be taken orally and is commercially available as 60-mg tablets, 180-mg controlled release tablets, a 5-mg/mL injectable solution, and a 60-mg/5 mL (240mL) syrup.^2,3

Read more about Mestinon (Pyridostigmine Bromide)

Immunosuppressive Therapy

When treatment goals are not met with pyridostigmine monotherapy, patients should be started on corticosteroids and/or another nonsteroidal immunosuppressive treatment. If corticosteroids are not contraindicated, a nonsteroidal immunosuppressive agent in conjunction with a steroidal agent should be initiated. Nonsteroidal immunosuppressive agents include azathioprine, intravenous immunoglobulin (IVIg), cyclosporine, mycophenolate mofetil, methotrexate, rituximab, eculizumab, and tacrolimus.⁴

Expert consensus opinion supports the use of azathioprine as first-line therapy and is backed up by strong evidence from randomized controlled trials; however, practice may vary according to physician and institutional preferences. A corticosteroid should be used as the initial immunosuppressive agent in ocular MG and may be coupled with a nonsteroidal agent if monotherapy has been ineffective.⁴

When treatment goals have been achieved, patients should undergo a gradual tapering of their corticosteroid followed by a tapering of their nonsteroidal agent to the minimal effective dose.¹

For refractory disease, cyclophosphamide and rituximab may be considered but should be administered only under the guidance of a highly trained physician with experience in managing refractory MG. Immune checkpoint inhibitors are currently being studied for use in MG and are currently reserved for patients with severe symptoms. Some patients will require immunosuppressive therapy for years or for life.¹

Thymectomy

Virtually all patients who have MG with a thymoma should undergo tumor removal and thymectomy. For patients between the ages of 18 and 50 years with non-thymomatous MG, thymectomy is performed as an elective procedure to avoid immunotherapy or minimize the dose and duration of immunotherapy, and to prevent hospitalization for disease exacerbations.⁴ Thymectomy should be strongly considered for patients who have acetylcholine receptor (AChR) antibodies or refractory disease, or who cannot tolerate immunotherapy. For prepubertal patients, thymectomy should be considered if they have generalized AChR-antibody-positive MG that does not respond to immunosuppressive therapy or to avoid the potential complications of immunosuppressive therapy.

Thymectomy may also be considered in patients with generalized MG without AChR antibodies if they fail to respond to immunosuppressive therapy or to prevent/curtail the adverse effects of therapy.¹ Thymectomy may be offered to patients who have ocular MG with AchR antibodies and contraindications or disease refractory to immunosuppressive agents.⁴ No evidence supports thymectomy in patients who are positive for MuSK, lipoprotein receptor-related protein 4 (LRP-4), or agrin antibodies.¹

Plasma Exchange and Intravenous Immunoglobulin

Plasma exchange (PLEX) and intravenous immunoglobulin (IVIg) are short-term treatment options when life-threatening respiratory insufficiency or dysphagia develops and a rapid response to therapy is required. In some cases, PLEX and IVIg may be necessary before the initiation of immunosuppressive treatment to prevent or minimize exacerbations. PLEX or IVIg may also be used preoperatively in patients with significant bulbar dysfunction or disease refractory to other treatments. PLEX and IVIg are probably equally effective in the treatment of severe generalized MG, and the selection of one over the other is based on individual patient factors and availability. For example, PLEX cannot be used in patients with sepsis and is more effective if the patient has MuSK antibodies. On the other hand, IVIg cannot be used in patients with renal failure, a hypercoagulable state, or hypersensitivity to IVIg and is less effective in mild MG or ocular MG.¹

References

1. 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

2. Mestinon, Regonol (pyridostigmine) dosing, indications, interactions, adverse effects, and more. Medscape. Accessed February 16, 2022.

3. MESTINON SYRUP Rx. MPR. Accessed February 16, 2022.

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 Debjyoti Talukdar, MD, on 2/14/2022.

Kyle Habet, MD

Kyle Habet, MD, is a physician at Belize International Institute of Neuroscience where he is a member of a multidisciplinary group of healthcare professionals involved in the care of patients with an array of neurological and psychiatric diseases. He is a published author, researcher and instructor of neuroscience and clinical medicine at Washington University of Health and Science.

Myasthenia Gravis