Simply Stated: MG Therapeutic Landscape

Myasthenia gravis (MG) is a chronic neuromuscular disease characterized by muscle weakness that worsens after activity and improves after rest. Most people with MG experience one of two forms, ocular or generalized. In ocular MG, weakness is limited to the muscles that move the eyes and eyelids. In generalized MG (gMG), weakness may affect eye and eyelid muscles, but also involves a combination of facial, limb, and breathing muscles. MG can occur at any age and affects about 37 out of every 100,000 people in the United States (US).

To learn more about the signs and symptoms of MG, see the previous blog post entitled Simply Stated: What is Myasthenia Gravis (MG)? and/or this comprehensive review article about MG.

While there is currently no cure for MG, many therapeutic options are available for affected people and the symptoms of MG can be controlled with treatment. Here, we provide an overview of the current therapeutic landscape for MG.

Considerations for MG therapies

Therapeutic development in MG has been guided by an understanding of the biology underlying the disease. In MG, the immune system produces antibodies that mistakenly attack components at the neuromuscular junction, impairing communication between nerves and muscles.

About 80-90% of people with MG have abnormal antibodies in their blood that attack the acetylcholine receptor (AChR) on muscle cells. This form of MG, called AChR MG, is often linked to abnormalities in the thymus, an immune organ located behind the breastbone. A dysfunctional thymus may fail to eliminate harmful immune cells that attack the body’s own tissues.

Some individuals who test negative for AChR antibodies have antibodies against another muscle cell receptor known as muscle-specific tyrosine kinase (MuSK). The MuSK MG subtype represents about 5-8% of MG cases and is less likely to involve the thymus.

Other antibodies (e.g., to LRP4) have been identified in some people with MG, though these forms are rare and not well understood. When no known antibodies are detected, the condition is referred to as seronegative MG.

Since MG is caused by irregular immune responses, many current therapeutic strategies target inflammation or aim to reduce the number of abnormal antibodies in the blood.

Overview of current MG therapies

Management of MG involves a range of therapies, each with unique benefits and limitations. The choice of treatment is influenced by patient age, disease severity, antibody status, and individual preferences, and is typically made through shared decision-making with a person’s care team. Modern therapies have considerably improved the prognosis for people living with MG.

Key categories of MG therapeutics include:

• Symptomatic treatments (anticholinesterase agents)
• Chronic immunosuppressive therapies (corticosteroids and steroid-sparing agents)
• Surgical therapy (thymectomy)
• Targeted therapies (complement inhibitors, B cell depletion, neonatal Fc receptor inhibitors)
• Rapid-acting immunomodulators (plasmapheresis, IVIG)

Symptomatic treatments

Cholinesterase Inhibitors

Cholinesterase inhibitors are typically the first drug of choice for the treatment of MG. These drugs have been used to treat MG since the early 1990s and can produce symptomatic relief within minutes. Pyridostigmine bromide (Mestinon) is the most commonly used cholinesterase inhibitor. Cholinesterase inhibitors work by boosting levels of acetylcholine (ACh), the signaling molecule released by nerve cells and detected by the AChR on muscle cells at the neuromuscular junction. Sometimes these drugs can cause side effects such as diarrhea, abdominal cramps, and/or excessive saliva. Many people with MG who are treated with cholinesterase inhibitors will eventually require escalation to immunosuppressive therapy.

Chronic immunosuppressive therapies

Corticosteroids

Corticosteroids, such as prednisone, are effective, relatively fast-acting agents that broadly suppress the immune system. These drugs can begin to work within weeks to months and are both widely available and cost-effective. Long-term use of corticosteroid therapy, however, can produce serious side effects, such as weakened bones, mood changes, weight gain, high blood pressure, and stunted growth in children. Prednisone is used as first-line immunotherapy, but is usually decreased over time and followed by transition to a steroid-sparing agent.

Steroid-Sparing Agents

Steroid-sparing agents in MG are immunosuppressive medications used to reduce or eliminate the need for long-term corticosteroids like prednisone.

Azathioprine (Imuran) is used to reduce AChR antibodies, but acts more slowly than prednisone, producing improvements after about 6–18 months. It is typically initiated at a low dose and gradually increased based on the patient’s needs. Side effects include bone marrow suppression, liver toxicity, and a rare risk of malignancy, requiring regular monitoring of blood counts and liver function.

Mycophenolate mofetil (CellCept) is an immunosuppressant therapy that is effective in about 75% of patients over time. It commonly causes gastrointestinal side effects like nausea, diarrhea, or abdominal discomfort, but also carries a rare risk of serious infections or malignancies.

Cyclosporine (Neoral, Sandimmune) is a fast-acting therapy that has a high response rate, but may cause high blood pressure, kidney toxicity, and growth of excessive body hair. This therapy is often used to treat more severe cases of MG in which cholinesterase inhibitors are ineffective. Cyclophosphamide (Cytoxan) is another therapy reserved for severe, refractory MG cases due to its significant toxicity.

Tacrolimus produces less kidney toxicity compared to cyclosporine, with possible side effects including hyperglycemia (too much glucose in the bloodstream), paresthesias (“pins and needles” sensation), and tremor.

Finally, methotrexate is considered a second-line agent for MG. This therapy suppresses immune activity by inhibiting DNA synthesis.

Surgical therapy

Surgical removal of the thymus, known as thymectomy, is recommended for patients with thymoma (tumor of the thymus gland), as well as for those with AChR gMG, with or without thymoma. The procedure is most effective in older adults with AChR MG without thymoma, with most experiencing remission or a reduced need for medication. In most people, improvement of MG symptoms after thymectomy may take months to years to become apparent. It is generally not recommended for people with MuSK MG or for young children.

Targeted therapies

To date, a handful of targeted therapies have been approved by the US Food and Drug Administration (FDA) to treat MG. These therapies fall into two categories, complement inhibitors and neonatal Fc receptor inhibitors.

Complement inhibitors

Complement inhibitors block part of the immune system that contributes to antibody-mediated damage at the neuromuscular junction in MG.

Eculizumab (Soliris), approved in October 2017, was the first complement inhibitor indicated for refractory AChR gMG. Ravulizumab (Ultomiris), a longer-acting form of eculizumab, received approval in April 2022. More recently, Zilucoplan (Zilbrysq), a self-administered subcutaneous (under-the-skin) complement inhibitor, was approved in October 2023 for AChR gMG.

Fc receptor (FcRN) inhibitors

This class of therapies works by accelerating the clearance of abnormal antibodies in MG.

The first Fc receptor inhibitor to treat AChR gMG, Efgartigimod (Vyvgart), was approved in December 2021. It was followed by a subcutaneous formulation (Vyvgart Hytrulo) in June 2023. Another Fc receptor inhibitor, Rozanolixizumab (Rystiggo), was approved in June 2023 for both AChR and MuSK gMG. Most recently, Nipocalimab (IMAAVY) was approved in April 2025 for people aged 12 and older with AChR or MuSK gMG.

Rapid-acting immunomodulators

Under some circumstances, such as before surgery or to treat a life-threatening complication of MG known as myasthenic crisis, rapid-acting treatments may be required.

People affected by myasthenic crisis experience extreme weakness of the bulbar (speech and swallowing) and/or respiratory (breathing) muscles, which can lead to respiratory failure. The first priority in managing this type of emergency is providing respiratory support, often through mechanical ventilation. Additional treatments typically include plasmapheresis and intravenous immuglobulin (IVIG) therapy to address the underlying immune system dysfunction.

Plasmapheresis (also called plasma exchange)

This therapy uses an intravenous (in-the-vein) line to remove antibodies from the blood.

IVIG therapy

In IVIG therapy, nonspecific antibodies (immunoglobulins) are injected into the bloodstream in order to stop the immune system from producing new antibodies, including the abnormal antibodies that contribute to MG.

These treatments bring about fast, but short-term, relief from MG.

Summary

Ultimately, the goal of management in MG is to decrease symptoms to their lowest point, while minimizing side effects from medications. Treatment decisions are based on the specific symptoms and disease course experienced by each person with the disease. In most cases, symptoms can be well-controlled with treatment, allowing people with MG to maintain good overall health and a high quality of life.

MDA’s Resource Center provides support, guidance, and resources for patients and families, including information about MG, open clinical trials, and other services. Contact the MDA Resource Center at 1-833-ASK-MDA1 or ResourceCenter@mdausa.org.