Therapies for patients with anti–muscle–specific tyrosine kinase antibody positive myasthenia gravis based on the pathophysiology

Abstract

Anti–muscle–specific tyrosine kinase antibody positive myasthenia gravis (MuSK MG) is less prevalent than anti–acetylcholine receptor antibody positive myasthenia gravis, yet a higher proportion of MuSK MG is resistant to treatments. For treatment, since anti–MuSK antibodies of the IgG4 subclass do not activate complement, complement inhibitors are inappropriate for use. High–dose intravenous immunoglobulin therapy is also unsuitable because its mechanisms do not align closely with the pathophysiology of MuSK MG. Currently, the initial treatment consists of corticosteroids and immunosuppressants, and FcRn inhibitors or plasmapheresis therapy are recommended for patients who do not respond to the initial treatment. The unapproved rituximab shows promise as the most effective treatment for resistant MuSK MG patients and is expected to become available soon in Japan. If these treatments do not improve the myasthenic conditions, new treatments currently under development, such as B–cell maturation antigen targeted chimeric antigen receptor (BCMA–CAR) T cell therapy and MuSK targeted chimeric autoantibody receptor (MuSK–CAAR) T cell therapy or other therapies, will be required.