Novel Treatments in Myasthenia Gravis

Abstract

Myasthenia gravis (MG) is the prototypical autoimmune disorder caused by specific autoantibodies at the neuromuscular junction. Broad-based immunotherapies, such as corticosteroids, azathioprine, mycophenolate, tacrolimus, and cyclosporine, have been effective in controlling symptoms of myasthenia. While being effective in a majority of MG patients many of these immunosuppressive agents are associated with long-term side effects, often intolerable for patients, and take several months to be effective. With advances in translational research and drug development capabilities, more directed therapeutic agents that can alter the future of MG treatment have been developed. This review focuses on the aberrant immunological processes in MG, the novel agents that target them along with the clinical evidence for efficacy and safety. These agents include terminal complement C5 inhibitors, Fc receptor inhibitors, B cell depleting agents (anti CD 19 and 20 and B cell activating factor [BAFF)]inhibitors), proteosome inhibitors, T cells and cytokine based therapies (chimeric antigen receptor T [CART-T] cell therapy), autologous stem cell transplantation, and subcutaneous immunoglobulin (SCIG). Most of these new agents have advantages over conventional immunosuppressive treatment (IST) for MG therapy in terms of faster onset of action, favourable side effect profile and the potential for a sustained and long-term remission.

Practice patterns in the management of myasthenia gravis: a cross-sectional survey of neurologists in the United States

“…Insurance coverage and formulary issues may have influenced neurologists' reported choices of tests and treatments. Because the range of treatment options for MG is broadening, it is likely that cost will become an even larger factor in treatment decisions (5). Survey results showed that current treatment decision-making often results in a higher cost burden for the patient and health care system: IVIg/SCIg was the most commonly reported second-line therapy for patients with AChR antibodypositive gMG after an NSIST failed to control their symptoms.…”

“…There are broadly accepted therapies for MG, although often with low levels of evidence to support their use (5) and, until recently, there were no international recommendations to guide care for MG. As treatment options continued to expand, improved strategies for managing this heterogeneous disease became necessary (6). Accordingly, a 15-member international task force was convened in 2013 by the Myasthenia Gravis Foundation of America (MGFA) to address this unmet need.…”

Rituximab for the Treatment of Myasthenia Gravis: A 2021 Update

“…6 Conventional therapies for the treatment of myasthenia gravis include cholinesterase inhibitors (e.g., pyridostigmine), which increase the amount of acetylcholine available at the neuromuscular junction, corticosteroids (e.g., prednisone), which are immunosuppressants, thymectomy, where the thymus gland is removed to stop the production of autoantibodies, and other immunomodulatory therapies (e.g., azathioprine, cyclosporine, IV immunoglobulin, and plasma exchange). [7][8][9] The goal of these therapies is to achieve stable disease where patients experience limited symptoms (i.e., minimal manifestation status). 10 Although many patients experience success with these approaches, approximately 10% of those with generalized myasthenia gravis are refractory to or are unable to tolerate conventional therapies.…”

Controversies in Ocular Myasthenia Gravis

“…Rituximab was very effective in the few OMG subjects treated so far (99,100) and, although evidence is scarce, may be considered in refractory disease. Lastly, OMG patients were not included in RCTs investigating novel therapeutic options based on complement inhibition or competition with IgG for the Fc neonatal receptor (101).…”