What is the initial treatment for myasthenia gravis?

Initial Treatment for Myasthenia Gravis

Pyridostigmine bromide administered orally two to four times a day is the first-line treatment for myasthenia gravis. 1, 2

Diagnostic Considerations Before Treatment

• Confirm diagnosis through:
  • Anti-acetylcholine receptor (AChR) antibody testing; if negative, consider muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP4) antibodies 1
  • Electrodiagnostic studies, with single-fiber electromyography being the gold standard (positive in >90% of ocular myasthenia cases) 1
  • Repetitive nerve stimulation (positive in only one-third of ocular myasthenia cases) 1
  • Tensilon (edrophonium) testing in a monitored setting with atropine available (95% sensitive for generalized myasthenia, 86% for ocular myasthenia) 1

Treatment Algorithm

Step 1: Symptomatic Treatment

• Start pyridostigmine at 30 mg orally three times a day 1
• Gradually increase to maximum of 120 mg orally four times a day as tolerated and based on symptoms 1, 3
• Note: About half of patients with strabismus-associated myasthenia show minimal response to pyridostigmine 1

Step 2: If Inadequate Response to Pyridostigmine

• Add corticosteroids (prednisone 1-1.5 mg/kg orally daily) 1
• 66-85% of patients show positive response to corticosteroids 1
• Wean based on symptom improvement 1

Step 3: For Refractory Cases or Long-term Management

• Consider immunosuppressive therapy with azathioprine 1, 4
• Other options include:
  • Newer agents like efgartigimod alfa-fcab (FDA approved for AChR-positive patients) 1
  • Rituximab for refractory cases 5, 4
  • Mycophenolate, methotrexate, or tacrolimus as second-line immunosuppressants 4

Step 4: For Myasthenic Crisis or Severe Exacerbations

• Intravenous immunoglobulin (IVIG) 2 g/kg IV over 5 days 1
• OR plasmapheresis for 5 days 1
• Hospitalization with possible ICU monitoring 1

Step 5: Consider Thymectomy

• Always indicated in presence of thymoma 1
• Beneficial in AChR antibody-positive generalized MG patients up to age 65 5, 4
• May substantially reduce symptoms for certain subpopulations 1

Special Considerations

• Medication Precautions: Avoid medications that can worsen myasthenia gravis:

  • β-blockers
  • IV magnesium
  • Fluoroquinolones
  • Aminoglycosides
  • Macrolides
  • Butalbital-containing medications like Firocet 1, 6

• Monitoring: Regular assessment of:

  • Pulmonary function (vital capacity and negative inspiratory force) 1
  • Bulbar function (speech, swallowing) 1
  • Need for dose adjustments 3, 5

• Disease Course: Remission or stabilization often possible after 2-3 years of treatment 1

• Multidisciplinary Care: Management requires collaboration between neurologists and ophthalmologists (especially for ocular symptoms) 1

Treatment Efficacy and Limitations

• Pyridostigmine provides only partial benefit for many patients 3
• Most patients eventually require long-term immunosuppressive therapies 3, 5
• Novel therapies targeting complement pathways or antibody-recycling pathways are being developed 5, 7
• Regular long-term specialized follow-up is needed due to disease fluctuations 4

Remember that treatment response varies among patients, and the goal should be to achieve remission or minimal manifestations of disease while minimizing medication side effects 5, 4.