What is the management of neuromyelitis optica?

Management of Neuromyelitis Optica Spectrum Disorder

Rituximab is the most effective first-line long-term immunosuppressive therapy for NMOSD, demonstrating superior relapse reduction compared to azathioprine and other immunosuppressants. 1

Acute Attack Management

Initiate high-dose intravenous methylprednisolone immediately at 1000 mg/day for 3-5 days as the first-line treatment for acute NMOSD attacks. 2, 1 Treatment delays beyond 2 weeks are associated with significantly poorer outcomes and increased risk of severe permanent neurological deficits. 2, 1

When Steroids Fail or Severe Presentation

• Add plasma exchange (PLEX) early in severe attacks or when response to IV steroids is inadequate within 5 days. 1 Clinical improvement occurs in 79.2% of NMOSD patients treated with plasmapheresis. 3, 4
• Do not wait for complete steroid failure—initiate PLEX promptly in patients presenting with light perception vision or worse, or those with extensive longitudinally extensive transverse myelitis affecting ≥3 vertebral segments. 4, 5

Long-Term Disease-Modifying Therapy

First-Line: Rituximab

Start rituximab at 375 mg/m² weekly for 4 weeks OR 1000 mg given twice, 2 weeks apart. 1 Rituximab reduces annualized relapse rates from 1.34 to 0.56 (p=0.0005) and improves EDSS scores by an average of 1.1 points over 2 years. 6

• Maintenance dosing consists of two infusions of 1 g rituximab at 15-day intervals when circulating CD19+ B cells reach 1%. 6
• In head-to-head trials, rituximab decreased relapse rates more effectively than azathioprine. 3, 4
• Among patients who failed azathioprine or mycophenolate, 73% switched to rituximab with only 10% showing poor response. 7

Alternative Immunosuppressants (When Rituximab Unavailable or Contraindicated)

Mycophenolate mofetil (MMF) at 1-3 g/day is the preferred alternative, demonstrating significant decreases in mean EDSS scores. 3, 1 MMF shows better tolerability than azathioprine in comparative studies. 3

Azathioprine at 2-3 mg/kg/day can be effective but has higher rates of side effects and treatment discontinuation compared to other options. 1 Approximately 34% of patients show poor response to azathioprine or MMF, defined as ≥2 relapses or ≥1 severe relapse. 7

Predictors of Poor Response to Azathioprine/MMF

Patients with these characteristics should be considered for rituximab as first-line therapy rather than azathioprine or MMF: 7

• Pre-treatment history of severe attacks (p<0.001)
• Younger age at disease onset (p=0.022)
• Elevated anti-aquaporin-4 antibody levels predict treatment failure with rituximab (p=0.03) 6

Newer FDA-Approved Targeted Therapies

Eculizumab, satralizumab, and inebilizumab have demonstrated efficacy in reducing relapse rates and represent additional options for refractory cases or when rituximab fails. 4

Monitoring Treatment Response

• Monitor AQP4 antibody levels as clearance correlates with treatment response and durable disease remission. 4
• Perform regular ophthalmological evaluations including visual acuity, visual fields, and funduscopy. 2, 1
• Obtain serial MRI of brain and spinal cord to detect new lesions before clinical relapse. 4
• Track EDSS scores at each visit to objectively measure disability progression or improvement. 3, 4
• Visual-evoked potentials can detect bilateral optic nerve damage before clinical manifestations. 2, 1

Critical Pitfalls to Avoid

Do not mistake NMOSD for multiple sclerosis—standard MS disease-modifying therapies (interferons, natalizumab, fingolimod) may worsen NMOSD outcomes. 4 Key distinguishing features include "cloud-like" enhancement on MRI, area postrema lesions, and longitudinally extensive transverse myelitis ≥3 vertebral segments. 4

Do not discontinue maintenance immunosuppression prematurely—relapses occur in 50-60% of patients during corticosteroid dose reduction without adequate maintenance therapy. 2, 1

Do not delay acute treatment—inadequate duration of acute treatment and failure to initiate PLEX early in severe cases lead to irreversible disability. 1

Test for MOG-IgG antibodies after first recurrence if AQP4 antibodies are negative, as MOG antibody disorder requires different management approaches. 2

Risk Factors for Poor Outcomes

• Extensive spinal cord MRI lesions at presentation 1
• Reduced muscle strength or sphincter dysfunction at onset 1
• Presence of antiphospholipid antibodies 1
• Delay in therapy initiation beyond 2 weeks 1
• Presentation with vision of light perception or worse, or residual acuity ≤20/50 after optic neuritis 5
• Simultaneous bilateral optic neuritis 5

Special Considerations

Autologous hematopoietic stem cell transplantation (AHSCT) is not recommended for NMOSD outside clinical trials, as 81% of patients experience relapse after AHSCT despite the availability of highly effective pharmacological treatments. 4

Ensure adequate contraception during all immunosuppressive treatment periods due to teratogenic risks. 4