The Expanding Therapeutic Landscape in Myasthenia Gravis

Myasthenia gravis (MG) is a rare autoimmune disorder caused by autoantibodies targeting postsynaptic proteins of the neuromuscular junction. Although conventional therapies can achieve remission or sufficient symptom control in most patients with generalized MG (gMG), approximately 10%-30% of patients remain treatment refractory with an increased risk of myasthenic crises and mortality. In addition, prolonged immunosuppression can cause undesirable side effects. Over the past decade, research has focused on identifying new therapeutic targets, which paved the way to advance the development of novel therapies. Rather than exerting broad immunosuppression, novel therapies selectively target specific components involved in the immunopathogenesis of MG, such as immunoglobulin G (IgG) production (B cell-depleting agents), IgG recycling (neonatal fragment crystallizable receptor, FcRn, blocker), and complement activation (complement inhibitors). Targeted therapies have been evolving exponentially since 2017, marking a new era in treatment strategies in gMG. They have emerged as potential steroid-sparing agents with robust efficacy and favorable safety profiles. Small cohorts have demonstrated the efficacy and tolerability of these therapies during myasthenic crisis and in patients with active thymoma. Although targeted therapies have generally comparable efficacy and safety, treatment plans should be individualized, and several factors should be considered before initiating these therapies, including pharmacological spectrum (complement inhibitors are effective only in acetylcholine receptor antibody-positive MG, while FcRn and B cell-depleting agents have broader spectra), convenience of administration, and cost-effectiveness. This monograph proposes an updated treatment algorithm in refractory gMG that integrates novel targeted therapies alongside standard immunosuppressant steroid-sparing agents.