Monograph: The Expanding Therapeutic Landscape in Myasthenia Gravis-Article

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Myasthenia gravis (MG) is an antibody-mediated disorder of the neuromuscular junction. While conventional treatments—including corticosteroids, other immunosuppressants, pyridostigmine, and thymectomy—control symptoms for many patients, an estimated 10%–30% have refractory or incomplete responses, and long-term immunosuppression can cause significant adverse effects.<br /><br />New targeted therapies act on specific disease mechanisms: B-cell–depleting agents reduce antibody production; neonatal Fc receptor (FcRn) blockers accelerate IgG breakdown; and complement inhibitors prevent damage to the neuromuscular junction. These treatments can improve function and reduce the need for corticosteroids or other immunosuppressants. FcRn blockers have a broad potential reach across antibody subtypes, whereas complement inhibitors are effective only in acetylcholine-receptor (AChR) antibody-positive MG. B-cell depletion may offer durable control but can increase infection risk.<br /><br />The proposed treatment approach is individualized. For AChR-positive generalized MG, conventional nonsteroidal immunosuppressants remain preferred initial steroid-sparing options because they are generally more affordable and convenient. If these are inadequate or poorly tolerated, an FcRn blocker or complement inhibitor may be considered, weighing antibody status, safety, administration preferences, and cost. Complement inhibitors require meningococcal vaccination and carry ongoing infection risk. For muscle-specific tyrosine kinase (MuSK) MG, early rituximab is recommended; FcRn blockade is an option if response is insufficient. Inebilizumab is approved for both AChR- and MuSK-positive disease, though longer-term evidence is needed.<br /><br />Small clinical reports suggest that targeted therapies may help in myasthenic crisis or active thymoma-associated MG, but evidence is limited, and these patients were excluded from pivotal trials. Head-to-head comparisons, long-term real-world safety and effectiveness data, and cost-effectiveness studies remain important unmet needs.

Keywords

myasthenia gravis

neuromuscular junction

nmj

antibody-mediated disorder

immunosuppressants

pyridostigmine

FcRn blockers

complement inhibitors

B-cell depletion

AChR-positive MG

MuSK-positive MG