Treatment of Neuromyelitis Optica Spectrum Disorder (NMOSD)

Introduction to NMOSD Treatment

The American Academy of Neurology recommends rituximab as the most effective treatment for neuromyelitis optica spectrum disorder, demonstrating superior reduction in relapse rates compared to azathioprine and other immunosuppressants 1, 2

High-dose intravenous methylprednisolone (IVMP) at 1000 mg/day for 3-5 days is the initial recommended treatment for acute NMOSD attacks, and treatment should be initiated promptly, as delay beyond 2 weeks is associated with poorer outcomes and increased risk of severe neurological deficit 3, 4
Plasma exchange (PLEX) should be initiated early in severe attacks or when response to steroids is inadequate, with clinical improvement in 79.2% of patients with NMOSD 1

Rituximab (RTX) is superior to azathioprine in reducing relapse rates in NMOSD patients, with a recommended dose of 375 mg/m² weekly for 4 weeks or 1000 mg × 2 weeks apart 1, 2
Mycophenolate mofetil (MMF) has demonstrated significant decrease in mean Expanded Disability Status Scale (EDSS) scores, with a recommended dose of 1-3 g/day 1, 5
Azathioprine (AZA) can be effective but has higher rates of side effects and discontinuation compared to other immunosuppressants, with a recommended dose of 2-3 mg/kg/day 2

Regular ophthalmological evaluations including visual acuity, visual fields, and funduscopy are necessary to monitor treatment response, and visual-evoked potentials may detect bilateral optic nerve damage before it becomes clinically apparent 3
Extensive spinal cord MRI lesions, reduced muscle strength or sphincter dysfunction at presentation, presence of antiphospholipid antibodies, and delay in therapy initiation (>2 weeks) are risk factors for poor outcomes 4
Inadequate duration of acute treatment, failure to initiate PLEX early in severe cases, and discontinuing maintenance therapy prematurely are treatment pitfalls to avoid, as relapses are common (50-60%) during corticosteroid dose reduction 4

The World of Neurosurgery recommends mycophenolate mofetil (MMF) at 1-3 g/day as a preferred alternative to rituximab, demonstrating significant decreases in mean EDSS scores 6
The World of Neurosurgery suggests that MMF shows better tolerability than azathioprine in comparative studies 6
The World of Neurosurgery notes that rituximab decreased relapse rates more effectively than azathioprine in head-to-head trials 6
Tracking EDSS scores at each visit is essential to objectively measure disability progression or improvement, as recommended by the World of Neurosurgery 6

Approximately two thirds of patients with Neuromyelitis Optica (NMO) are seropositive for AQP4-IgG antibodies, which is associated with a better prognosis due to a more homogeneous presentation compared to seronegative patients 7
Between 20-50% of patients have concomitant autoimmune diseases 7

Rituximab is the most effective first-line treatment for preventing relapses in NMO, demonstrating superiority over azathioprine and other immunosuppressants 7, 8
Eculizumab and ravulizumab (anti-complement) reduce relapse rates, with over 95% of patients remaining relapse-free during follow-up, and are approved for AQP4-Ab+ NMO 8
Satralizumab (anti-IL-6) and inebilizumab (anti-CD19) have also shown efficacy in reducing relapse rates 8

Despite the effectiveness of rituximab, 25-66% of patients still experience relapses, highlighting the importance of continued therapy 7

In patients with neuromyelitis optica spectrum disorder receiving rituximab as first‑line preventive therapy, 25 %–66 % still experience relapses, indicating that continuous immunosuppressive treatment is required to maintain disease control. 9

AHSCT is not recommended for NMOSD outside of clinical‑trial settings because the evidence base is limited and several highly effective pharmacologic options (e.g., anti‑complement or anti‑CD19 agents) are already available. 10