The aim of MG treatments is to achieve MGFA minimal manifestations or no symptoms or functional limitations (10,11).
Conventional treatments
Conventional treatments for MG include symptomatic and immunosuppressive therapies.
- Symptomatic treatments: cholinesterase inhibitors (g., pyridostigmine) slow down the hydrolysis of acetylcholine in the synaptic cleft. They are included in the initial treatment of MG. The dose should be adjusted based on symptoms and side effects.
- Immunosuppressive therapies: Immunosuppressive therapies are indicated when therapeutic goals are not achieved with cholinesterase inhibitors alone. Immunosuppressive treatments encompass glucocorticoids and non-steroidal immunosuppressants. Non-steroidal immunosuppressive agents that can be used in MG include azathioprine, cyclosporine, mycophenolate mofetil, methotrexate, and tacrolimus. Non-steroidal immunosuppressive agents should be added to corticosteroids in cases of significant side effects, insufficient treatment response, or when the corticosteroid dose cannot be reduced due to relapses.
Adjunct therapies
- Plasma exchange and intravenous immunoglobulins can be used as short-term treatments for patients with refractory generalized MG with life-threatening symptoms, such as respiratory deficiency or dysphagia.
- Resection of the thymus (thymectomy) is required if thymoma or thymic enlargement are detected by imaging. Thymectomy should be considered early in the disease for non-thymomatous, generalized MG patients with AChR antibodies, aged 18 to 50 years (12).
Biologics:
In addition to FcRn blockers, several biologics are currently used in the treatment of refractory MG.
- Rituximab is a chimeric monoclonal antibody targeting the CD20 protein expressed on the surface of B cells (except for progenitor B cells and mature plasma cells, which do not express it). Binding of rituximab to CD20-expressing cells results in their depletion by triggering antibody-dependent cellular cytotoxicity through the activation of NK cells, antibody-dependent cellular phagocytosis by activated macrophages, and complement-dependent cytotoxicity related to the activation of the classical complement pathway leading to membrane attack complex formation. The efficacy of rituximab in refractory AChR-positive MG is uncertain, whereas it should be considered as an early therapeutic option in patients with anti-MuSK autoantibodies.
- Eculizumab is a humanized monoclonal antibody targeting the C5 component of the complement system. Binding of eculizumab to C5 inhibits the terminal pathway of complement activation, preventing the formation of the membrane attack complex and reducing the damage caused by complement activation triggered by autoantibodies in MG. Eculizumab is currently approved for AChR positive refractory generalized MG.
- Ravulizumab is a humanized monoclonal antibody derived from eculizumab that was engineered to extend its duration of action. This was accomplished by introducing four point mutations, including two in the Fc region and two in the complementarity-determining regions (CDRs) of the variable region, the latter reducing target-mediated drug disposition, an elimination pathway of therapeutic antibodies associated with high-affinity binding to the target, promoting their elimination (13). Therefore, ravulizumab is administered every 8 weeks
- Zilucoplan is a macrocyclic peptide that binds to C5 and inhibits its cleavage, thereby preventing the formation of membrane attack complex. Zilucoplan is administered subcutaneously daily and is approved for the treatment of adults with generalized MG.
