Advances in autoimmune myasthenia gravis management

Abstract

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder with no cure and conventional treatments limited by significant adverse effects and variable benefit. In the last decade, therapeutic development has expanded based on improved understanding of autoimmunity and financial incentives for drug development in rare disease. Clinical subtypes exist based on age, gender, thymic pathology, autoantibody profile, and other poorly defined factors, such as genetics, complicate development of specific therapies. Areas covered: Clinical presentation and pathology vary considerably among patients with some having weakness limited to the ocular muscles and others having profound generalized weakness leading to respiratory insufficiency. MG is an antibody-mediated disorder dependent on autoreactive B cells which require T-cell support. Treatments focus on elimination of circulating autoantibodies or inhibition of effector mechanisms by a broad spectrum of approaches from plasmapheresis to B-cell elimination to complement inhibition. Expert commentary: Standard therapies and those under development are disease modifying and not curative. As a rare disease, clinical trials are challenged in patient recruitment. The great interest in development of treatments specific for MG is welcome, but decisions will need to be made to focus on those that offer significant benefits to patients.

Cross‐sectional analysis of the Myasthenia Gravis Patient Registry: Disability and treatment

“…Although advances have been made in understanding of disease pathogenesis and treatment, many patients have MG exacerbations, which often require hospitalization, and disease‐ and treatment‐related morbidity remains high . Common treatment regimens for MG include relatively benign, but often inadequate, cholinesterase inhibitors, surgical removal of the thymus, and immunomodulatory or immunosuppressive treatments (high‐dose corticosteroids, cyclosporine, azathioprine, rituximab, mycophenolate mofetil, intravenous immunoglobulin [IVIg], plasmapheresis [PLEx], and eculizumab), each with their unique adverse‐effect profiles . Despite the many treatment options, an estimated 15% to 20% of MG patients are considered treatment refractory.…”

“…Despite the many treatment options, an estimated 15% to 20% of MG patients are considered treatment refractory. Although national and international consensus guidelines have been established, there is limited understanding of how patients are being treated in everyday clinical practice …”

Immunosuppressive and monoclonal antibody treatment for myasthenia gravis: A network meta‐analysis

“…As an alkylating agent, CTX is widely applied in severe autoimmune disorders including MG . The hematopoietic and immune system could be repopulated with endogenous stem cells after intermittent high‐dose CTX . Although QMGS was not performed, muscle strength was improved with statistical significance.…”

“…The incidence of AEs between CTX and PLA did not reveal statistical significance. However, compared with PLA, CTX usually induces more severe AEs including diarrhea, hemorrhagic cystitis, infection, and infertility with carcinogenic, teratogenic potential …”

“…Recently, monoclonal antibodies are emerging therapeutic alternatives for MG. Monoclonal antibodies to CD20 (MabThera TM ), C5b9 (Soliris TM ) are beneficial drug to treat severe generalized MG. 5,6 So far, traditional meta-analysis has evaluated the efficacy and safety of the above single or double intervention. [7][8][9] However, none of them had included adequate assessment of comparative effectiveness of immunotherapies.…”