Contemporary treatment of myasthenia gravis

Idiopathic autoimmune myasthenia is the most common disease of neuromuscular synapses. The pathogenesis is autoimmune, associated with the occurrence of antigenic targets in nicotinic acetylcholine receptors (AChR) and related proteins, on postsynaptic membranes. It is caused by antibodies against neuromuscular synapse components and impaired neuromuscular transmission.Clinically, it presents with fluctuating muscle weakness. Treatment depends on age, thymus pathology, presence and type of antibodies, form and activity of disease. It is subdivided into symptomatic treatment, which facilitates neuromuscular transmission, and diseasemodifying treatment, which targets the underlying pathological immune response. Symptomatic treatment is the first choice for most patients. It is conducted with acetylcholinesterase inhibitors, which reversibly block the acetylcholinesterase enzyme and slow the hydrolysis of acetylcholine. Immunomodulatory (disease course modifying) therapy is used to suppress immune-mediated destruction of acetylcholine receptors and postsynaptic membrane architecture. Corticosteroids and classical immunosuppressants (primarily azathioprine) are the drugs of first choice for immunosuppression in patients with active generalized or ocular myasthenia. They are used when the effect of anticholinesterase agents alone or in combination with thymectomy is unsatisfactory. Refractory to standard treatment are 10% of patients. Monoclonal antibodies targeting the immune system have advantages over conventional immunosuppressive treatment in terms of faster onset of action, favorable side-effect profile and the potential for durable and long-term remission. Some of the drugs currently being investigated include C5 terminal complement inhibitors, Fc receptor inhibitors, B cell depleting agents (anti-CD19 and anti-20 and B cell activating factor inhibitors), proteosome inhibitors, cytokine inactivating monoclonal antibodies, monoclonal antibodies inactivating T cell function and subcutaneous immunoglobulin administration. Thymectomy is mandatory in almost all patients with thymoma, but not during disease exacerbation.In conclusion, advances in the elucidation of the pathophysiological mechanisms of myasthenia have led to new classes of drugs modifying the course of the disease.