Prognosis for Neuromyelitis Optica Spectrum Disorder (NMOSD)
Untreated NMOSD has a devastating prognosis with approximately 50% of patients becoming wheelchair users and blind, and one-third dying within 5 years of their first attack. 1 However, with modern treatments, outcomes can be significantly improved.
Disease Course and Disability Progression
NMOSD follows a distinct pattern of progression compared to other demyelinating disorders:
- Relapsing course: The majority of patients (82.4%) follow a relapsing course, while 17.6% may have a monophasic course 2
- Attack-related disability: Unlike multiple sclerosis, disability in NMOSD accumulates primarily through relapses rather than progressive deterioration 1
- No secondary progression: A progressive clinical course is very unusual in NMOSD 1
Timeline to Disability Milestones
Based on long-term follow-up data from Serbia, the median time to reach disability milestones is 2:
- EDSS 4.0 (significant disability but fully ambulatory): 6.5 years
- EDSS 6.0 (requires walking assistance): 11.9 years
- EDSS 7.0 (restricted to wheelchair): 22.0 years
Prognostic Factors
Several factors influence the prognosis of NMOSD:
Negative Prognostic Factors:
- Higher baseline EDSS score: Associated with faster progression to EDSS 4.0,6.0, and 7.0 2
- Shorter interval between first attacks: Predicts faster progression to EDSS 4.0 and 6.0 2
- Delayed treatment initiation: Longer time to treatment start is associated with faster progression to EDSS 7.0 2
- Poor visual acuity at disease onset: Predicts faster progression to severe visual deficit 2
- Optic neuritis or combined opticospinal onset: Leads to earlier severe visual deficits compared to myelitis-only onset 2
- Persistent AQP4 antibodies: Continued presence of antibodies is associated with disease activity 3
Positive Prognostic Factors:
- Early immunosuppressive treatment: Significantly reduces relapse risk and motor disability 4
- Clearance of AQP4 antibodies: Associated with durable disease remission 3
Treatment Impact on Prognosis
The introduction of targeted therapies has dramatically improved the prognosis of NMOSD:
Conventional Immunosuppressants:
- Mycophenolate mofetil (MMF) and azathioprine (AZA): Significantly reduce relapse rates, motor disability, and mortality compared to no treatment 4
- These treatments delay progression of disability and extend time to first relapse 4
Newer Targeted Therapies:
- Eculizumab: Demonstrates 94% relative risk reduction in relapse and 96% reduction in annualized relapse rate compared to placebo 5
- Other biologics: B-cell depleting therapies (rituximab, inebilizumab), anti-IL-6 receptor antibodies (tocilizumab, satralizumab), and complement inhibitors have shown effectiveness in preventing relapses 6, 7
Special Therapeutic Considerations
Hematopoietic Stem Cell Transplantation (HSCT):
- Mixed outcomes: In a registry analysis of 16 NMOSD patients, progression-free survival at 3-5 years was only 48%, with 81% experiencing relapse at a median of 7 months post-transplant 3
- More promising results: A prospective open-label study using a complex cyclophosphamide-based protocol with plasmapheresis and rituximab showed 90% progression-free survival at 5 years, with 80% of patients free from relapses and immunosuppressive treatment 3
- Reduced indication: The role of HSCT has diminished due to the availability of highly effective pharmacological treatments 3
Monitoring and Management
Antibody Monitoring:
- Elimination of AQP4 antibodies may serve as a biomarker of treatment response 3
- However, regular monitoring of MOG-IgG titers for relapse prediction is not currently recommended due to practical challenges 3
Treatment Selection:
- Early immunosuppressive treatment is crucial for improving prognosis 4, 2
- Treatment choice should consider individual risk factors, including infection susceptibility, cytopenias, and infusion-related reactions 6
Conclusion
With early diagnosis and appropriate treatment, the previously grim prognosis of NMOSD has improved substantially. The key to favorable outcomes lies in prompt initiation of immunosuppressive therapy following diagnosis, careful monitoring, and aggressive treatment of relapses to prevent residual disability.