What are the treatment options for achieving remission in patients with myasthenia gravis (Myasthenia Gravis, MG)?

Treatment Options for Achieving Remission in Myasthenia Gravis

The treatment of myasthenia gravis should aim for complete remission, defined as the absence of clinical symptoms and systemic inflammation, using a stepwise approach starting with pyridostigmine and escalating to immunosuppressive therapies as needed. 1

First-Line Treatment

• Pyridostigmine (Acetylcholinesterase Inhibitor)
  • Starting dose: 30 mg orally three times daily
  • Can be gradually increased to maximum of 120 mg four times daily (up to 600 mg daily)
  • Used for symptomatic control, may be sufficient for mild disease 1, 2

Second-Line Treatment

• Corticosteroids

  • Indicated for patients with more than mild disease
  • Prednisone 0.5-1.5 mg/kg orally daily
  • Positive response rate: 66-85% of patients
  • Often initiated concurrently with steroid-sparing agents 1

• Steroid-Sparing Immunosuppressants

  • Should be started concurrently with corticosteroids to minimize steroid exposure
  • Options include:
    • Azathioprine: 2 mg/kg of ideal body weight in divided doses
    • Methotrexate: 15 mg weekly
    • Mycophenolate mofetil: 500 mg twice daily increasing to 1000 mg twice daily 1

Thymectomy

• Indicated for patients with thymoma and AChR antibody-positive generalized MG up to age 65
• Remission rates of approximately 11.6% reported after thymectomy
• MGTX trial showed clear evidence of benefit in AChR antibody-positive generalized MG 1, 2
• Factors associated with better response to thymectomy:
  • Age <60 years
  • <2 years of preoperative symptoms
  • Low doses of pyridostigmine 3

Treatment for Refractory Disease or Crisis

• Intravenous Immunoglobulin (IVIG)

  • Dosage: 2 g/kg over 5 days 1

• Plasmapheresis

  • Typically administered for 5 days 1

• Complement Inhibitors

  • Eculizumab (FDA-approved for generalized MG in AChR antibody-positive patients)
  • Dosing: 900 mg weekly for first 4 weeks, followed by 1200 mg for fifth dose, then 1200 mg every 2 weeks 4, 5

• Rituximab

  • Particularly effective for MuSK antibody-positive MG 5

Monitoring for Remission

• Regular neurological assessments
• Pulmonary function tests including negative inspiratory force (NIF) and vital capacity (VC)
• Close monitoring for patients with NIF -20 to -60 cm H₂O 1

Important Considerations

1. Medication Avoidance

   • Avoid medications that can worsen myasthenia:
     • β-blockers
     • IV magnesium
     • Fluoroquinolones
     • Aminoglycosides
     • Macrolides 1

2. Anesthetic Considerations

   • Safe agents: Propofol, Sevoflurane, isoflurane, Fentanyl, remifentanil, Lidocaine, bupivacaine
   • Avoid: Atracurium, mivacurium, and succinylcholine
   • Rocuronium is preferred as it can be antagonized with sugammadex 1

3. Supplemental Dosing During Plasmapheresis

   • For patients on eculizumab receiving plasmapheresis or plasma exchange:
     • 600 mg supplemental dose within 60 minutes after each session 4

Special Populations

• Ocular MG

  • Early treatment with corticosteroids recommended when ocular motility is abnormal and fails to respond to symptomatic treatment
  • 85% rate of remission or minimal manifestations with immunosuppression 2, 6

• Thymoma-Associated MG

  • Requires thymectomy
  • Lower remission rates (47%) compared to other MG forms
  • May require more aggressive immunosuppression 6

The goal of treatment should be to achieve complete remission or minimal manifestations status, with careful monitoring for treatment-related adverse effects and appropriate adjustments to therapy as needed.