What is the treatment for Myasthenia Gravis (MG)?

Treatment of Myasthenia Gravis

Begin with pyridostigmine 30 mg orally three times daily as first-line symptomatic therapy, titrating up to a maximum of 120 mg four times daily based on response, and escalate to corticosteroids (prednisone 1-1.5 mg/kg daily) for Grade 2 or higher symptoms, reserving IVIG or plasmapheresis for severe Grade 3-4 exacerbations with respiratory compromise. 1, 2

Symptomatic Treatment: First-Line Therapy

• Pyridostigmine (Mestinon) is the cornerstone of initial symptomatic management for all patients with myasthenia gravis, as it is FDA-approved specifically for this indication 3
• Start at 30 mg orally three times daily and gradually increase based on clinical response and tolerability 1, 2
• Maximum dosing is 120 mg orally four times daily 1, 2
• Approximately 50% of patients with ocular myasthenia show minimal response to pyridostigmine alone and will require escalation to immunosuppressive therapy 4, 5

Immunosuppressive Therapy: Second-Line Treatment

Grade 2 Disease (Mild Generalized Weakness)

• Add corticosteroids directly if pyridostigmine provides insufficient symptom control 1, 2
• Initiate prednisone at 1-1.5 mg/kg orally daily 1, 2
• Taper gradually based on symptom improvement 1, 2
• 66-85% of patients show a positive response to corticosteroids 4, 5
• Hold immune checkpoint inhibitors if MG is immune-related, and may resume only if symptoms resolve to Grade 2 or less 1

Grade 3-4 Disease (Severe Generalized Weakness or Myasthenic Crisis)

• Immediately hospitalize with ICU-level monitoring capability 1, 2
• Initiate IVIG 2 g/kg total dose over 5 days (0.4 g/kg/day × 5 days) OR plasmapheresis for 5 days 1, 2
• Continue corticosteroids concurrently during acute treatment 1, 2
• Permanently discontinue immune checkpoint inhibitors if MG is immune-related 1
• Perform frequent pulmonary function assessments with negative inspiratory force and vital capacity monitoring 1, 2
• Conduct daily neurologic evaluations 1, 2

Critical Medications to Avoid

Strictly educate patients to avoid medications that worsen myasthenic symptoms: 1, 2, 4

• β-blockers
• Intravenous magnesium
• Fluoroquinolone antibiotics
• Aminoglycoside antibiotics
• Macrolide antibiotics

Surgical Intervention: Thymectomy

• Thymectomy is indicated in all cases with thymoma 1, 5
• Consider thymectomy for specific age-based and immune-based characteristics, as it may substantially reduce clinical symptoms even without thymoma 1, 5
• 10-20% of patients with acetylcholine receptor antibody-positive MG have a thymoma 6

Diagnostic Workup Requirements

Before initiating treatment, confirm diagnosis with: 1, 2, 5

• Acetylcholine receptor (AChR) and antistriated muscle antibodies in blood
• If AChR antibodies are negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies
• Pulmonary function testing with negative inspiratory force and vital capacity
• Electrodiagnostic studies including neuromuscular junction testing with repetitive stimulation and/or jitter studies
• Ice pack test for ocular symptoms (highly specific for MG) 1, 4

Treatment Algorithm by Disease Severity

Ocular MG Only (MGFA Class 1)

• Start pyridostigmine 30 mg three times daily 1, 2
• Monitor closely, as 50-80% progress to generalized MG within a few years 1, 5

Mild Generalized Weakness (MGFA Class 2)

• Optimize pyridostigmine dosing first 1, 2
• Add prednisone 1-1.5 mg/kg daily if symptoms persist 1, 2

Moderate to Severe Generalized Weakness (MGFA Class 3-4)

• Hospitalize with ICU monitoring 1, 2
• IVIG 2 g/kg over 5 days OR plasmapheresis 1, 2
• Continue corticosteroids and pyridostigmine 1, 2

Myasthenic Crisis (MGFA Class 5)

• ICU admission with intubation capability 1, 2
• IVIG or plasmapheresis immediately 1, 2
• Frequent respiratory monitoring 1, 2

Important Clinical Pitfalls

• Do NOT use IVIG for chronic maintenance therapy - it is reserved only for acute exacerbations or crisis situations 2
• Pupils are characteristically NOT affected in myasthenia gravis; pupillary involvement should prompt evaluation for alternative diagnoses such as third nerve palsy 4
• Regular pulmonary function assessment is crucial, as respiratory compromise can develop rapidly 1, 2
• Immune checkpoint inhibitor-associated myasthenia gravis may be monophasic and may not require additional corticosteroid-sparing agents 1, 2

Long-Term Management Considerations

• Plan regular neurology consultation and follow-up to adjust treatment 2
• Consider steroid-sparing immunosuppressive agents (azathioprine, mycophenolate mofetil) for patients requiring chronic corticosteroid therapy 5, 6
• Newer targeted therapies (efgartigimod alfa-fcab, rituximab, eculizumab) are available for refractory cases 5, 7
• Remission or stabilization is often possible after 2-3 years of treatment 5