What is the treatment for myasthenia gravis?

Treatment of Myasthenia Gravis

First-Line Symptomatic Treatment

Start pyridostigmine at 30 mg orally three times daily and titrate gradually to a maximum of 120 mg four times daily based on symptom response and tolerability. 1, 2, 3

• Pyridostigmine is an acetylcholinesterase inhibitor that enhances neuromuscular transmission and is FDA-approved for myasthenia gravis treatment 3
• This medication provides symptomatic relief but typically offers incomplete improvement, with approximately 50% of patients with ocular myasthenia showing minimal response 1
• Common side effects include flatulence, urinary urgency, muscle cramps, blurred vision, and hyperhidrosis, with 91% of patients reporting at least one side effect 4
• Pyridostigmine is suitable as monotherapy for patients with mild, non-progressive generalized disease 5

Second-Line Immunosuppressive Therapy

For patients with Grade 2 or higher symptoms inadequately controlled by pyridostigmine alone, initiate corticosteroids with prednisone 1-1.5 mg/kg orally daily. 1, 2

• Corticosteroids demonstrate efficacy in approximately 66-85% of patients with myasthenia gravis 1
• Taper corticosteroids gradually based on symptom improvement rather than following a fixed schedule 2
• Consider adding azathioprine as adjunctive therapy with corticosteroids for patients requiring long-term immunosuppression 1, 6

Treatment of Myasthenic Crisis (Grade 3-4)

For patients with severe generalized weakness or respiratory compromise, immediately hospitalize with ICU-level monitoring and administer IVIG 2 g/kg total dose over 5 days (0.4 g/kg/day × 5 days) or plasmapheresis. 1, 2

• Continue corticosteroids and pyridostigmine concurrently during acute crisis management 2
• Perform frequent pulmonary function assessments with negative inspiratory force and vital capacity monitoring 1, 2
• Conduct daily neurologic evaluations throughout hospitalization 2
• IVIG and plasmapheresis show comparable efficacy for acute exacerbations 6

Critical Caveat on IVIG Use

IVIG should NOT be used for chronic maintenance therapy in myasthenia gravis—reserve it exclusively for acute exacerbations or crisis situations. 2

• Multiple guidelines consistently recommend against chronic IVIG maintenance therapy 2
• IVIG is indicated only for symptomatic patients resistant to or intolerant of immunosuppressive therapy during acute episodes 2

Medications to Strictly Avoid

Educate all patients to avoid β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides, as these medications can precipitate myasthenic crisis. 1, 2

• Barbiturate-containing medications (e.g., butalbital) should also be avoided 2
• Any patient requiring surgery must have serum anti-acetylcholine receptor antibody levels measured preoperatively to prevent respiratory failure during anesthesia 1

Monitoring Requirements

Perform regular pulmonary function assessment in all patients with generalized myasthenia gravis to detect early respiratory compromise. 1, 2

• Monitor for worsening bulbar symptoms (dysphagia, dysarthria), respiratory difficulties, and diplopia 2
• Plan regular neurology follow-up to adjust treatment based on clinical response 2
• Instruct patients to seek immediate medical attention for significant increases in muscle weakness 2

Newer Therapeutic Options

For patients with anti-acetylcholine receptor antibody-positive disease refractory to standard therapy, consider complement blockade agents (eculizumab, ravulizumab, zilucoplan) or neonatal Fc receptor antagonists (efgartigimod, rozanolixizumab). 7

• These novel therapies represent alternatives for treatment-resistant cases but should be reserved for patients who have failed conventional immunosuppression 7

Thymectomy Considerations

Perform thymectomy for all patients with thymoma-associated myasthenia gravis, and consider it for non-thymomatous patients under age 55-60 within the first 6-12 months of disease duration. 6

• Approximately 30-50% of patients with thymomas have myasthenia gravis, and in 20% of thymoma patients, mortality is related to myasthenia 1

Practical Management Algorithm

• Mild symptoms (Grade 1): Pyridostigmine monotherapy 30-120 mg four times daily 1, 2
• Moderate symptoms (Grade 2): Add prednisone 1-1.5 mg/kg/day if pyridostigmine insufficient 2
• Severe symptoms (Grade 3-4): ICU admission + IVIG or plasmapheresis + continue corticosteroids + frequent pulmonary monitoring 2
• Refractory disease: Consider azathioprine, cyclosporine, mycophenolate mofetil, or novel biologics 6, 7