<p>Generalized myasthenia gravis (gMG) can be managed with traditional therapies such as steroids and other immunosuppressants, as well as a growing number of targeted therapies. The careful use and combination of these therapies can help reduce patient symptoms and improve their outcomes.</p>

In thinking about traditional therapies, the medications that I often use first for most patients with gMG are AChEIs. This class of medications works within hours and can be effective for gMG. After AChEIs, I use immunomodulators or immunosuppressants, and treatment depends on many patient and medication factors, including comorbidities, antibody status, severity of disease, side-effect profiles, how quickly the medications work, and insurance approvals. For most patients with gMG, I move on to steroids, which work within days to weeks, are oral, and are easy to prescribe. The downsides are the many short- and long-term side effects that limit their long-term use.

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Along with steroids, I often use a steroid-sparing agent such as azathioprine, mycophenolate mofetil, tacrolimus, or methotrexate. These medications are also easy to prescribe and allow for a reduction in steroid dosage, but they can take 3 to 12 months to take effect. Fast-acting therapies for myasthenic crisis are intravenous immunoglobulin and plasma exchange. These treatment options are invasive, but they work within hours to days and are quite effective. Another treatment option is thymectomy. The thymus is involved in the pathophysiology of AChR antibody–positive MG. In patients with MG, approximately 15% have thymoma, and another 50% to 70% have thymic hyperplasia. Thymectomy benefits take time (approximately 2-3 years), but the procedure allows patients to require fewer medications and have better treatment outcomes.

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For AChR antibody–positive gMG, the thymus plays a role, and, even if a chest computed tomography scan is negative, patients benefit from a thymectomy, particularly those who are younger than age 50 years. AChR antibody–positive gMG is also the patient population for which most of our newer agents are US Food and Drug Administration (FDA) approved. AChR antibodies are typically IgG1 or IgG3, which activate the complement cascade. Several C5 inhibitors are FDA approved for AChR antibody–positive disease, and FcRn inhibitors also can be used in this population.

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Seronegative gMG may present the same as AChR antibody–positive disease, so patients with seronegative disease could have AChR antibodies that are not detectable based on our current diagnostic tools or antibodies targeting different proteins at the neuromuscular junction. I treat patients with seronegative disease similarly to how I treat patients with AChR antibody–positive disease. However, our newer agents are not FDA approved for the seronegative population, so sometimes insurance will not approve these medications.

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Patients with MuSK antibody–positive gMG tend to be younger women who have bulbar-predominant disease and disease that can be quite refractory. However, these patients respond very well to rituximab, which is used off-label, and to prednisone and plasma exchange. The FcRn inhibitors rozanolixizumab and nipocalimab are FDA approved for MuSK and AChR antibody–positive gMG. For patients with MuSK antibody–positive gMG, my go-to is B-cell depletion or FcRn inhibition.

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I have seen a wide range of comfort and expertise with treating MG among general neurologists. Some colleagues refer patients to me when they do not respond to AChEIs. Others feel very comfortable using newer therapies and may refer for a one-time consultation and continue management locally.