Abstract: 
Generalized myasthenia gravis (gMG) is a postsynaptic neuromuscular junction disorder that results in fatigable muscle weakness. The traditional treatment approach includes the use of acetylcholinesterase inhibitors, corticosteroids, and steroid-sparing immunosuppressant therapies (ISTs) for chronic management, whereas exacerbations and crises are managed with intravenous immunoglobulin (IVIg) and plasma exchange (PLEX). Over the past six years, four new therapeutic agents with novel immunological mechanisms of action - complement and neonatal Fc receptor (FcRn) inhibition - were approved as a result of clinically significant improvement in gMG symptoms of those treated with these newer agents in Phase 3 clinical trials. At present, it is unclear when and in whom to initiate these therapeutic agents and how to integrate them into the current treatment paradigm. When selecting a newer therapeutic agent, we use a simple equation: Value = Clinical Improvement/ (Cost + Side Effects + Treatment Burden), which guides our decision making. We consider using these novel therapeutic agents in two specific
clinical situations. Firstly, the newer agents are fast-acting, suggesting they can be used in clinically unstable patients as “bridge therapy,” and secondly, they provide additional options for those patients considered treatment-refractory. There are downsides, however, including treatment cost, unique side effect profiles, and intravenous and subcutaneous drug administration (through for some, this may be an advantage). As additional drugs enter the marketplace with unique mechanisms of action, routes of administration and dosing schedules, the placement of the novel therapeutic agents in the gMG treatment algorithm will likely evolve.

Dr. Gwathmey has served as a paid consultant for Alexion Pharmaceuticals, argenx, and UCB, she has served on the speakers’ bureau for Alexion Pharmaceuticals. Huanghe Ding has no conflicts of interest. Dr. Hehir is a paid consultant for Alexion, Argenx, UCB, Janssen, and Immunovant. Dr. Hehir has also received honorarium as Associate Editor of MedLink Neurology, educational speaker for Medscape, and a Guest Editor of Continuum. Dr. Silvestri has served as a paid consultant for Alexion Pharmaceuticals, argenx, UCB, and Immunovant; he has served on speakers’ bureaus for Alexion Pharmaceuticals, argenx, and UCB. Conflicts have been resolved according to ACCME standards.