Update for Hospital and Health-System Pharmacists on Newer Therapeutics to Optimize Management of Patients with Generalized Myasthenia Gravis
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About 85% of patients with generalized myasthenia gravis (gMG)--an autoimmune disease of the neuromuscular junction caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and therefore cause weakness and fatigue of skeletal and bulbar muscles--have demonstrable IgG autoantibodies. These autoantibodies exert a direct pathogenic effect that results in impaired neuromuscular transmission. Most currently available treatments, including corticosteroids and nonsteroidal immunosuppressive therapies, broadly suppress the immune system and do not selectively target those IgG autoantibodies central to generalized myasthenia gravis pathophysiology. In addition, these treatments often provide only limited symptom relief and—especially in the case of steroids—are associated with treatment-limiting side-effects. A new approach that addresses that unmet need involves predictable lowering levels of pathogenic autoantibodies. In MG, the neonatal Fc receptor (FcRn) is a major factor regulating the serum levels of IgG antibodies. While FcRn-mediated half-life extension is beneficial for IgG antibody responses against pathogens, it also prolongs the serum half-life of IgG autoantibodies and thus promotes tissue damage in autoimmune diseases such as MG. A mutated antibody to the FcRn can block IgG-associated damage and potentially improve outcomes and treatment tolerance in generalized MG. The FDA has now approved drugs that target FcRn-mediated antibody recycling and can improve patient outcomes while reducing the need for corticosteroids.
Pharmacy professionals play an important role in the new era of recently approved therapeutic options to treat patients with gMG. Whether working in the hospital, in a neuromuscular clinic, or in an infusion center, pharmacists play a key role in supporting patient care, preparing and delivering these medications, and evaluating comorbidities and concomitant medications of interest. It is important for pharmacists involved in the care of patients with gMG to be well-informed about the pathophysiology of gMG, the reason why FcRn-targeted therapy can be beneficial, and about the multiple ways pharmacists can help improve patient comfort, satisfaction, and outcomes with this therapy.
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