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Myasthenia Gravis: Treatment

• Pyridostigmine (Mestinon) is the usual first line treatment for MG.
• Prednisone and Cyclosporine A are used for long-term immunosuppression when further benefit is needed and relatively rapid onset of benefit is desired. Prednisone is the most effective treatment for ocular MG.
• Azathioprine provides long-term immunosuppression with relatively few side effects. However, it has a long latency before benefit begins, and some patients do not improve at all.
• Mycophenolate mofetil may be a useful substitute for azathioprine with fewer side effects and a shorter latency of action. More experience is required.
• Plasma exchange (PE) and Human immune globulin are used when MG patients have life-threatening signs such as respiratory insufficiency or dysphagia and a very rapid response to treatment is desired. PE is preferred.
• Thymectomy is performed for long-term benefit in patients aged 8 to 55 with generalized MG.

• Usual adult doses
  • Pills:
    • 60 mg tid to 120 mg q3h
    • Higher does: Virtually never effective; Often have side effects
  • Timespan pills:
    • 90 to 180 mg qhs
    • Use at bedtime
    • Many cholinergic side effects if used more often than qhs
  • Liquid: 60 mg pyridostigmine bromide per teaspoonful (5 mL)
• Anti-AChE drugs: Childhood doses
• Indications: First line treatment in most MG patients
• Advantages: Few serious side effects
• Disadvantages
  • Cholinergic symptoms & crisis
  • Effective in only some patients

• Usual doses
  • Inpatient: starting
    Begin at 20 mg qd
    • Increase by 5 mg every 2 to 3 days
    • Maximum: 50 mg qd
  • Outpatient: starting
    Begin at 5 mg qd
    • Increase by 5 mg every week
    • Maximum: Significant clinical improvement, or 50 mg qd
  • Maintenance
    
    • Start taper after: 3 to 6 months; or clinical improvement begins
    • Taper slowly
      1. Initially by 5 mg on alternate days q2 to 4 weeks until 50 mg and 10 mg
         
      2. Then by 2.5 mg on alternate days q2 weeks to 50 mg and 0 mg
         
      3. Then taper high day dose by 2.5 mg q 4 weeks
         
      4. Minimum dosage is qod if possible.
    • MG will recur in virtually all patients if Prednisone is stopped without additional immunosuppression
• Indications
  

  Glucocorticoid Side Effects

  Cushingoid features Weight gain Bone: Avascular necrosis; Osteoporosis Myopathy: Myosin-loss; Type II atrophy Diabetes Skin: Acne; Striae Hypertension Psychosis & Mood change Pseudotumor cerebri Glaucoma Infection

  • Significant disability due to disease symptoms
  • Effective long term immunosuppression in pyridostigmine resistant patient
  • Relatively rapid effect desired
  • Refractory ocular MG
• Monitor: Weight; Blood pressure; Blood glucose & electrolytes; Ocular exam
• Advantages
  • Short onset of action (1 to 3 months)
  • Effective in most patients
  • Can be used in pregnancy
• Disadvantages
  • Transient initial severe exacerbation, usually after 1 to 3 weeks (2% to 5%)
  • Many long-term side effects

Azathioprine (Imuran)

• Usual doses
  Initial: 2.5 to 3 mg/kg qd
  • Maintenance: 1.5 to 2.5 mg/kg qd
• Indications
  • Long-term immunosuppression when rapid onset is not necessary
  • Steroid sparing
  • Minimize side effects
• Monitor: Hct, WBC & platelets; Liver function
• Advantages
  • Few subjective side effects
• Disadvantages
  • Serious side effects
    • Increased risk of malignancy: Not demonstrated in MG patients
    • Reduced RBC, WBC, Platelets: dose related or idiosyncratic
    • Liver dysfunction
    • Flu-like reaction: 20% to 30% of patients
      Azathioprine cannot be restarted
    • Teratogenic
  • Long onset of action (6 to 24 months)
  • Moderate to high cost

• Usual doses
  Initial: 2.5 mg/kg bid
  Maintenance: Lowest effective dose
  • May be effective below "therapeutic range" in serum
• Indications
  • Long-term immunosuppression
  • Especially when prednisone cannot be used or is ineffective
  • When relatively rapid response (months) is desired
• Monitor
  • Renal function; Blood pressure
  • Blood level: Drawn exactly 12 hours after previous dose
• Advantages: Short onset of action (1 to 3 months)
• Disadvantages:
  • Serious side effects: Most are dose related
    • Nephrotoxicity
    • ?Increased risk of malignancy
    • Teratogenic
  • Many drug interactions
    • Especially avoid: NSAIDs; Amphotericin B and nephrotoxic drugs
  • High cost
  • Needs serum level monitoring
    • Trough levels: Obtain 12 hours after last dose

• Usual dose: 1 g twice daily
• Indications
  • Long-term immunosuppression
  • Especially when prednisone cannot be used or is ineffective
• Advantages
  • Moderate onset of action (1 to 12 months)
  • Few side effects: Low risk for late malignancies; No major organ toxicity
• Disadvantages
  • High Cost
  • Onset of action may be delayed 6 to 12 months
  • Limited experience of utilization for MG

• Dose: 5 exchanges over 9 to 10 days
• Indications
  • Acutely ill MG patient
  • Pre-thymectomy in patient with respiratory or bulbar involvement
  • NOT for long-term treatment
• Advantages
  • Very short onset of action (3 to 10 days)
  • Probably more effective in crisis than human immune globulin
• Disadvantages
  • Requires specialized equipment & personnel
  • Complications more frequent in elderly
  • High cost
  • Benefit only short-term (weeks)
  • More side effects than human immune globulin

• Dose: 2 grams/kg (over 2 to 5 days)
• Indication
  • Acutely ill MG patient
  • NOT for long-term treatment
• Advantages
  • Easily administered: Widely available; Dosage over 2 days
  • Serious side effects rare
  • Short onset of action
  • Fewer side effects than plasma exchange
• Disadvantages
  • Benefits not well demonstrated
  • High cost
  • Benefit only short-term
  • Probably less effective in crisis than

• Indications
  • Generalized MG in patients aged ~8 to 55
  • Thymoma
  • Only indicated as an elective procedure
• Approaches
  • Transsternal
    • Standard method
    • Always with thymoma
  • Transcervical
    • Only when performed with direct visualization of thymus
• Advantages
  • Low short-term & minimal long-term morbidity
• Disadvantages of thymectomy
  • Benefits poorly documented
  • Only very-long term benefit likely
  • Experienced surgeon necessary