What are the treatment options for myasthenia gravis?

Treatment of Myasthenia Gravis

Start all patients with pyridostigmine bromide 30 mg orally three times daily as first-line therapy, titrating up to a maximum of 120 mg four times daily based on symptom response. 1, 2, 3

Stepwise Treatment Algorithm

First-Line: Symptomatic Treatment

• Pyridostigmine (acetylcholinesterase inhibitor) is FDA-approved and should be initiated immediately upon diagnosis 3
• Begin at 30 mg orally three times daily and gradually increase based on clinical response and tolerability 4, 1, 2
• Maximum dosing is 120 mg orally four times daily 4, 1, 2
• Approximately 50% of patients with ocular myasthenia show minimal response to pyridostigmine alone and will require escalation 4, 1

Second-Line: Corticosteroids

• Add prednisone 1-1.5 mg/kg orally daily if pyridostigmine provides insufficient symptom control (Grade 2 symptoms) 4, 1, 2
• 66-85% of patients demonstrate positive response to corticosteroids 4, 5
• Taper gradually based on symptom improvement 4, 2
• Do not delay corticosteroid initiation in Grade 2 patients with persistent symptoms despite optimized pyridostigmine 2

Third-Line: Steroid-Sparing Immunosuppression

• Azathioprine is the established steroid-sparing agent for patients requiring long-term immunosuppression 4, 1, 5
• Consider for patients with inadequate response to corticosteroids or those needing to reduce steroid burden 5
• Other immunosuppressive agents (cyclosporine, cyclophosphamide) may be used by treating neurologists 4

Acute Crisis Management (Grade 3-4)

• Immediately hospitalize with ICU-level monitoring for severe generalized weakness or respiratory compromise 4, 2
• Administer IVIG 2 g/kg total dose over 5 days (0.4 g/kg/day × 5 days) OR plasmapheresis for 5 days 4, 1, 2
• Continue corticosteroids concurrently during IVIG or plasmapheresis 4, 2
• Perform frequent pulmonary function assessments with negative inspiratory force and vital capacity monitoring 4, 1, 2
• Conduct daily neurologic evaluations 4, 2
• Permanently discontinue immune checkpoint inhibitors if MG is drug-induced 4

Critical Medications to Avoid

Strictly avoid the following medications that worsen myasthenic symptoms: 4, 1, 2

• β-blockers 4, 1, 2
• Intravenous magnesium 4, 1, 2
• Fluoroquinolone antibiotics 4, 1, 2
• Aminoglycoside antibiotics 4, 1, 2
• Macrolide antibiotics 4, 1, 2

Surgical Considerations

Thymectomy

• Indicated in all patients with thymoma (10% of MG patients have thymoma) 4, 5
• May substantially reduce symptoms in certain subpopulations with generalized myasthenia gravis 4, 5
• Consider for patients with generalized disease, particularly those with early-onset MG 4

Strabismus Surgery

• Only consider after disease stabilization, typically 2-3 years of medical treatment 4, 5
• Reserve for patients with persistent diplopia not manageable with prisms 4, 5
• Use extreme caution with anesthetic agents given risk of respiratory muscle weakness 4

Newer Targeted Therapies

Efgartigimod alfa and other neonatal Fc receptor antagonists represent emerging options for refractory cases 1, 5

• Reserve for patients who fail standard immunosuppressive therapy 1
• Complement blockade agents (eculizumab, ravulizumab, zilucoplan) are additional options for treatment-resistant disease 6

Essential Diagnostic Workup

Before initiating treatment, confirm diagnosis with: 4, 1, 2

• Acetylcholine receptor (AChR) antibodies and antistriated muscle antibodies in blood 4, 1
• If AChR antibodies negative, test for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 4, 1
• Pulmonary function testing with negative inspiratory force and vital capacity 4, 1, 2
• Electrodiagnostic studies including repetitive nerve stimulation and/or single-fiber EMG (>90% sensitivity for ocular myasthenia) 4, 1
• Consider MRI of brain/spine depending on symptoms to exclude CNS involvement 4

Common Pitfalls to Avoid

• Do not use IVIG for chronic maintenance therapy - it is only indicated for acute exacerbations or crisis situations 2
• Do not delay escalation to corticosteroids in Grade 2 patients with inadequate pyridostigmine response 2
• Do not overlook respiratory monitoring - 50-80% of patients with initial ocular symptoms develop generalized myasthenia within a few years 1, 5
• Do not miss concurrent myocarditis - check CPK, troponin T, ECG, and echocardiogram if respiratory insufficiency or elevated CPK present 4

Monitoring Requirements

• Regular neurology consultation to adjust treatment as disease evolves 4, 2
• Frequent pulmonary function assessment especially in patients with generalized disease or respiratory symptoms 4, 1, 2
• Daily neurologic evaluations during acute exacerbations 4, 2
• Monitor for disease progression from ocular to generalized myasthenia 1, 5