Integrating FcRn and Complement System Therapies for Generalized Myasthenia Gravis

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Program Description

This enduring webcast addresses the autoimmune pathogenesis of gMG and the integration of targeted immune-mediated therapies. The activity will focus on:

Autoimmune pathogenesis of gMG – Autoimmune pathology in gMG disease subtypes is governed by divergent mechanisms of immunopathology

• Anti-AChR autoantibodies – ~85% of gMG cases
• Anti-MuSK autoantibodies – 5-10% of gMG cases
• Anti-LRP4 antibodies
• Anti-agrin autoantibodies
• Seronegative gMG

Etiology and Classification – gMG occurs in genetically susceptible individuals, and precipitating factors include infections, immunization, surgeries, and drugs.

• Early-onset gMG: Age at onset less than 50 years with thymic hyperplasia
• Late-onset gMG: Age at onset greater than 50 years with thymic atrophy
• Thymoma-associated gMG
• The gMG with anti-MuSK antibodies
• Ocular gMG: Symptoms only from periocular muscles
• The gMG with no detectable AChR and MuSK antibodies

Pathophysiology – The pathophysiologic mechanisms in gMG depend on the type of antibodies present.

• Nicotinic acetylcholine receptors (n-AChR) gMG
  • Muscle-specific kinase (MuSK) gMG
  • Lipoprotein-related protein 4 (LPR4) gMG
• Clinical classification of gMG
  • The Myasthenia Gravis Foundation of America (MGFA) clinical classification divides gMG into 5 main classes based on the clinical features and the disease severity.

Evaluation – The diagnosis of gMG is primarily clinical. Laboratory investigations and procedures usually aid clinicians in confirming clinical findings.

• Serologic Tests
• Electrophysiologic Tests
  • Repetitive nerve stimulation (RNS) test
  • Single-fiber electromyography (SFEMG) test
• Edrophonium (Tensilon) test
• Ice-pack test
• Imaging: Chest computed tomography (CT) or magnetic resonance imaging (MRI)

Treatment/Management of gMG

• Symptomatic treatment
• Immunosuppressive treatment
• Intravenous immunoglobulins (IVIG)/plasmapheresis
• Thymectomy

Target-specific Therapies

• FDA-approved treatments for gMG include:
  • FcRn Inhibitors – Efgartigimod, Rozanolixizumab
  • Complement System Inhibitors – Eculizumab, Zilucoplan, and Ravulizumab
• Ongoing clinical trials
  • Nipocalimab – The mAb targeting FcRn
  • Batoclimab – The mAb targeting FcRn

Intended Audience

Neurologists, neuromuscular specialists, ophthalmologists, primary care physicians, advanced practice providers (physician assistants and nurse practitioners), and nurses who manage patients with gMG.

Commercial Supporter

Supported by an educational grant from UCB Inc.