Rituximab for NMOSD with MOG-IgG Positivity
Critical Diagnostic Clarification
You cannot have both NMOSD and MOGAD simultaneously—these are mutually exclusive diagnoses. AQP4-IgG/MOG-IgG "double-positive" results are extremely rare and should prompt retesting for both antibodies using alternative methodologies, as false positives occur with suboptimal assays 1, 2. If truly double-positive after confirmatory cell-based assays, treat based on the dominant clinical phenotype and the antibody with higher titer.
Treatment Approach Based on Antibody Status
If AQP4-IgG Positive (True NMOSD)
Rituximab is highly effective for AQP4-IgG-positive NMOSD and should be initiated immediately after the first attack. 3, 4, 5
Induction Regimen
- Use 1000 mg IV infusions given 15 days apart (total 2000 mg) 6, 7
- This was the most common regimen used across Latin American centers (83.1% of patients) and showed comparable efficacy to other dosing schemes 6
- Alternative: 375 mg/m² weekly for 4 weeks, though less commonly used 5
Maintenance Strategy
- Redose every 6 months with 1000 mg IV infusions (two doses, 15 days apart) 6, 7
- Regular dosing is critical: irregular treatment (intervals >9 months twice, or >12 months once) significantly increases annualized relapse rate (ARR), EDSS scores, and severe relapses 7
Expected Outcomes
- Median ARR decreases from 1.1 pre-treatment to 0 post-treatment 4
- 82.3% of AQP4-IgG+ patients remain relapse-free when considering relapses occurring >1 month after RTX initiation 7
- 72% remained relapse-free over 72 weeks in randomized controlled trial 5
Treatment Failures
- 77% of relapses occur either within the first 6 months of starting rituximab OR with delayed/missed doses and B-cell reconstitution 4
- Do not allow treatment gaps or B-cell reconstitution 4, 7
- Risk factors for relapse: AQP4-IgG titer ≥320 at onset, severe demyelinating episodes in first attack, higher pre-RTX ARR 7, 4
If MOG-IgG Positive (True MOGAD)
Rituximab is less effective for MOGAD than for AQP4-IgG-positive NMOSD, but can reduce relapses in relapsing disease. 3, 4
Key Differences from NMOSD
- Median ARR decreases from 1.9 pre-treatment to 0.3 post-treatment (less robust reduction than NMOSD) 4
- 61% of MOGAD patients experienced relapses on rituximab versus 28% of NMOSD patients 4
- Hazard ratio for relapse on rituximab: 2.8 times higher in MOGAD compared to NMOSD (95% CI: 1.5-5.2, p=0.001) 4
- Only 54% of MOGAD treatment failures were associated with delayed doses or B-cell reconstitution, suggesting other mechanisms 4
Treatment Recommendations
- Reserve rituximab for relapsing MOGAD only, not monophasic disease 3
- Use same dosing as NMOSD if initiated: 1000 mg IV every 15 days, repeated every 6 months 4, 6
- Consider alternative therapies (IVIG, oral immunosuppressants) given lower efficacy 3
Monitoring Requirements
B-Cell Monitoring Strategy
- Monitor CD27-positive B-cells rather than total CD19-positive B-cells for more personalized dosing 8
- Redose when CD27+ B-cells >0.05% of lymphocytes for first 2 years, then >0.1% thereafter 8
- This approach extends median inter-dose interval from 8.8 to 15.9 months without compromising efficacy 8
Safety Monitoring
- Screen for infections requiring hospitalization (occurred in 13% of patients) 4
- Monitor for IgG hypogammaglobulinemia (occurred in 17% of patients, median onset 5.4 years) 4
- No deaths or severe adverse events directly attributable to rituximab in major studies 5, 8
Critical Pitfalls to Avoid
- Never use MS-approved therapies (beta-interferons, natalizumab, fingolimod) in either condition—they can cause severe exacerbations 3, 9
- Do not allow rituximab treatment gaps or B-cell reconstitution in AQP4-IgG+ patients 4, 7
- Implement slow steroid taper after acute attacks—rapid taper causes flare-ups in both conditions 3, 1
- Retest antibodies if initially negative but clinical suspicion remains high, especially during acute attacks or 1-3 months after plasma exchange/IVIG 3