Current and Future Standards in Treatment of Myasthenia Gravis

Abstract

Summary: Myasthenia gravis (MG) is a prototypic antibodymediated neurological autoimmune disorder. Herein we characterize modern treatment algorithms that are adapted to disease severity, and introduce the current principles of escalating strategies for MG treatment. In non-thymoma patients younger than about 50 years of age and with generalized weakness, a complete early (but not urgent) thymectomy is considered as state-of-the-art on the basis of circumstantial evidence and expert opinion. In up to 10% of patients, MG is associated with a thymoma (i.e., is of paraneoplastic origin). The best surgical type of procedure is still under debate.Myasthenic crisis is best treated by plasmapheresis, mostly combined with immunoabsorption techniques. Intravenous immunoglobulins are a reasonable alternative, but a shortage in supplies and high prices limit their use. In generalized MG, a wide array of immunosuppressive treatments has been established, although not formally tested in double-blind, prospective trials. With regard to immunosuppression, azathioprine is still the standard baseline treatment, often combined with initial corticosteroids. In rare patients with an inborn hepatic enzyme deficiency of thiomethylation, azathioprine may be substituted by mycophenolate mofetil. Severe cases may benefit from combined immunosuppression with corticosteroids, cyclosporine A, and even with moderate doses of methotrexate or cyclophosphamide. Tacrolimus is under investigation.In refractory cases, immunoablation via high-dose cyclophosphamide followed by trophic factors such as granulocyte colony-stimulating factor has also been suggested. In the future we may face an increased use of novel, B-cell, or T-celldirected monoclonal antibodies.

Outcomes of Therapeutic Plasma Exchange; One Year Single Center Experience

“…Ralf et al [16], and Linda et al [17] are in agreement with our results and stated that all patients had immediate benefits of TPE with good tolerance and relatively less coasty but effective than other modalities. While Skeie et al [18] stated that their study failed to show pronounced difference between TPE and IVIG, yet it may be due to relative small sample size of their study.…”

A randomized and controlled study comparing immunoadsorption and plasma exchange in myasthenic crisis

“…Long-term treatment consists of acetylcholinesterase inhibitors, steroids, and other immunosuppressive drugs or immunomodulating therapies like intravenous immunoglobulins, and surgical thymectomy [1][2][3]17]. Interventional strategies for the rapid elimination of pathogenic antibodies can be offered by therapeutic apheresis [e.g., plasma exchange (PE) or immunoadsorption (IA)] [17,18].…”

Tacrolimus Monotherapy: A Promising Option for Ocular Myasthenia Gravis

“…Anticholinesterase agents are the basic symptomatic treatment for MG, which partially compensates for the reduced safety margin at the neuromuscular junction; these agents may be sufficient in rare cases of mild MG with purely ocular involvement. Corticosteroid immunosuppressant drugs are the mainstay of disease-modifying therapy for MG; however, the adverse effects of corticosteroids include osteoporosis, hypertension, exacerbation or precipitation of diabetes mellitus, gastrointestinal ulcers, cataracts, and opportunistic infection [1]. Therefore, an alternative to corticosteroid therapy is needed, especially in elderly patients.…”