What is the treatment for myasthenia gravis?

Treatment for Myasthenia Gravis

The first-line treatment for myasthenia gravis is pyridostigmine bromide administered orally two to four times daily, followed by corticosteroids if symptoms persist, with more severe cases requiring IVIG or plasmapheresis. 1

Diagnostic Workup

Before initiating treatment, a thorough diagnostic evaluation should be performed:

• Antibody testing:

  • Acetylcholine receptor (AChR) antibodies
  • Anti-striated muscle antibodies
  • If AChR antibodies negative, test for muscle-specific kinase and lipoprotein-related 4 antibodies 1

• Functional assessment:

  • Pulmonary function tests (negative inspiratory force and vital capacity)
  • Electrodiagnostic studies including repetitive nerve stimulation and single-fiber electromyography (considered gold standard with >90% sensitivity) 1

• Rule out concurrent conditions:

  • CPK, aldolase, ESR, CRP to evaluate for myositis
  • Cardiac evaluation if respiratory insufficiency or elevated CPK/troponin 1

• Neurological consultation is essential for diagnosis confirmation and treatment planning 1

Treatment Algorithm

1. Symptomatic Treatment

• Pyridostigmine bromide (first-line):
  • Starting dose: 30 mg PO three times daily
  • Gradually increase to maximum of 120 mg four times daily as tolerated 1
  • Note: About half of patients with strabismus-associated myasthenia show minimal response 1
  • Monitor for cholinergic side effects (gastrointestinal symptoms, hyperhidrosis, muscle cramps) 2

2. Immunosuppressive Therapy

• Corticosteroids:

  • Indicated if symptoms persist despite pyridostigmine
  • Prednisone 1-1.5 mg/kg PO daily 1
  • 66-85% of patients show positive response 1
  • Gradually taper based on symptom improvement

• Steroid-sparing agents:

  • Azathioprine (proven effective) 1, 3
  • Other options: cyclosporine A, cyclophosphamide 3

3. For Moderate to Severe Disease (Grade 3-4)

• Hospital admission (may require ICU monitoring) 1
• IVIG: 2 g/kg over 5 days 1
• OR Plasmapheresis for 5 days 1
• Continue corticosteroids concurrently 1
• Daily neurologic evaluation and frequent pulmonary function assessment 1

4. Newer Targeted Therapies

• Complement inhibitors:

  • Eculizumab, ravulizumab (approved in Russia) 4
  • Consider for refractory cases 3, 4

• Neonatal Fc receptor antagonists:

  • Efgartigimod (FDA approved for AChR-positive patients) 1, 3
  • Rozanolixizumab 3

5. Surgical Intervention

• Thymectomy:

  • Always indicated if thymoma present
  • May substantially reduce symptoms in certain subpopulations 1

• Strabismus surgery:

  • Consider after 2-3 years of treatment when disease is stabilized
  • May require multiple surgeries 1

Important Precautions

• Avoid medications that can worsen myasthenia:

  • β-blockers
  • IV magnesium
  • Fluoroquinolones
  • Aminoglycosides
  • Macrolides 1

• Monitor for cholinergic crisis:

  • Characterized by increasing muscle weakness that can affect respiratory muscles
  • May require immediate withdrawal of cholinesterase inhibitors
  • Atropine may be used to manage cholinergic side effects 5
  • Consider hyoscyamine to manage cholinergic side effects (like AV block) while maintaining neuromuscular benefit 6

• Differentiate between myasthenic crisis and cholinergic crisis:

  • Myasthenic crisis (disease worsening) requires increased anticholinesterase therapy
  • Cholinergic crisis (medication overdose) requires withdrawal of anticholinesterase drugs 5
  • May require Tensilon (edrophonium) testing in a monitored setting with atropine available 1

Treatment Monitoring

• Regular assessment of clinical response
• Pulmonary function monitoring, especially in moderate-severe cases
• Consider monitoring erythrocyte-bound acetylcholinesterase activity as an alternative to plasma pyridostigmine concentrations 7
• Be aware that 91% of patients on pyridostigmine report side effects, with gastrointestinal symptoms being most common 2

Long-term Management

• Remission or stabilization often possible after 2-3 years of treatment 1
• ICPi-associated myasthenia gravis may be monophasic; additional corticosteroid-sparing agents may not be required 1
• Adjust treatment based on disease severity and response to therapy