What are the treatment options for Neuromyelitis Optica (NMO)?

Treatment Options for Neuromyelitis Optica (NMO)

The treatment of Neuromyelitis Optica Spectrum Disorder (NMOSD) requires prompt and aggressive intervention with high-dose corticosteroids as first-line therapy, followed by plasma exchange if response is inadequate, and long-term immunosuppression with rituximab, mycophenolate mofetil, or azathioprine to prevent relapses. 1

Acute Treatment of NMO Relapses

First-Line Treatment

• High-dose intravenous methylprednisolone (IVMP): 1g/day for 3-5 days 2
  • Should be initiated as early as possible, ideally within the first few hours of symptom onset
  • Delay in treatment (>2 weeks) is associated with severe neurological deficits 1
  • Neurological response typically occurs within a few days to 3 weeks

Second-Line Treatment

• Plasma exchange (PLEX):
  • Indicated when response to IVMP is inadequate 1, 3
  • Some evidence suggests better outcomes when compared to IVMP alone 3
  • Can be synchronized with intravenous cyclophosphamide for enhanced efficacy 1
  • Typically 5-7 exchanges over 7-14 days

Alternative Acute Treatments

• Adrenocorticotropic hormone (ACTH):

  • May be considered for patients who fail systemic steroids 4
  • Dosing: 80 U/day intramuscularly for 7 days for acute relapse, followed by 80 U every 2 weeks for maintenance 4
  • Limited evidence but may have fewer/less severe adverse effects compared to IVMP

• Intravenous immunoglobulin (IVIG):

  • May be considered in cases where PLEX is contraindicated
  • Less evidence for efficacy compared to PLEX

Long-Term Prevention of Relapses

First-Line Options

• Rituximab:

  • Monoclonal antibody targeting CD20+ B cells
  • Has shown significant improvement in psychiatric manifestations in refractory cases 1
  • Dosing: 375 mg/m² weekly for 4 weeks or 1000 mg given twice with 2-week interval, followed by maintenance doses

• Mycophenolate mofetil:

  • Effective for maintenance therapy 5
  • Typical dose: 1000-3000 mg/day in divided doses

• Azathioprine:

  • Effective in controlling inflammation in severe cases 1, 5
  • Typical dose: 2-3 mg/kg/day
  • Should be combined with prednisone initially

FDA-Approved Targeted Therapy

• Eculizumab:
  • FDA-approved for treatment of NMOSD in adult patients who are anti-aquaporin-4 (AQP4) antibody positive 6
  • Complement inhibitor that targets the terminal complement protein C5
  • Requires meningococcal vaccination at least 2 weeks prior to first dose
  • Available only through a restricted REMS program due to risk of meningococcal infections

Treatment Algorithm

1. Diagnosis confirmation:

   • Test for NMO-IgG (aquaporin-4) antibodies
   • MRI of brain and spinal cord (look for longitudinally extensive transverse myelitis)
   • Rule out other demyelinating disorders

2. Acute attack management:

   • Initiate high-dose IVMP (1g/day for 3-5 days) immediately
   • If inadequate response within 3-5 days, proceed to plasma exchange
   • Consider ACTH for patients who fail IVMP and decline other treatments

3. Long-term prevention:

   • Initiate immunosuppressive therapy promptly after acute treatment
   • Options include rituximab, mycophenolate mofetil, or azathioprine
   • For AQP4-positive patients, consider eculizumab
   • Continue maintenance therapy indefinitely as relapses are common (50-60%) during corticosteroid tapering 1

Special Considerations

• Screening: Test for hepatitis B and C before initiating immunosuppressive therapy 5
• Pregnancy: Treatment should be modified for pregnant patients
• Monitoring: Regular follow-up with clinical assessment and MRI every 6-12 months
• Relapses: Treat promptly as they can result in severe residual disability 3
• Poor prognostic factors:
  • Extensive spinal cord MRI lesions
  • Reduced muscle strength or sphincter dysfunction at presentation
  • Presence of antiphospholipid antibodies
  • Delay (>2 weeks) in initiation of therapy 1

Emerging Therapies

• Bevacizumab: May limit inflammation during NMO relapse by reducing blood-brain barrier disruption 7
• Ublituximab and HBM9161: Currently under investigation in clinical trials 3

The management of NMO requires aggressive and prompt treatment to prevent irreversible neurological damage. Early intervention with high-dose corticosteroids and, if necessary, plasma exchange, followed by long-term immunosuppression is critical for improving outcomes and reducing disability.