NOMADMUS
(2026)Objective
To describe the evolution of diagnosis, therapeutic strategies, disease activity, and long-term disability in AQP4+NMOSD and MOGAD in France from 2010 to 2024 using the nationwide NOMADMUS registry.
Study Summary
• In AQP4+NMOSD, rituximab use rose (32.6% → 43.6%) while azathioprine/mycophenolate fell (51.6% → 40.3%); rituximab exposure was associated with lower risk of reaching EDSS 6 (HR 0.38, 0.21–0.68, p<0.001)
• Older age at onset raised the risk of EDSS 6 in AQP4+NMOSD (HR 1.04, p<0.001); neither factor influenced MOGAD
• MOGAD had a better disability trajectory than AQP4+NMOSD: EDSS 3 at 5y 2.8% vs 20%; EDSS 6 at 5y 0.94% vs 7.4%
• Methylprednisolone was used in ~97% of acute relapses in both groups; PLEX use increased over time (AQP4+NMOSD 28.7% → 54.5%)
Intervention
None — observational nationwide registry cohort (no assigned intervention)
Inclusion Criteria
Patients in the French NOMADMUS cohort (nested in OFSEP) across 98 centers with AQP4-IgG seropositive NMOSD (2015 criteria) or MOG-IgG seropositive MOGAD (2023 criteria).
Study Design
Arms: AQP4+NMOSD (n=769) vs MOGAD (n=957)
Patients per Arm: AQP4+NMOSD: 769; MOGAD: 957
Outcome
• Rituximab exposure associated with lower risk of EDSS 6 in AQP4+NMOSD (HR 0.38; 95% CI 0.21–0.68; p<0.001)
• Risk of reaching EDSS 3 or 6 was lower in MOGAD than AQP4+NMOSD (EDSS 3 at 5y: 2.8% vs 20%; EDSS 6 at 5y: 0.94% vs 7.4%)
• Time to diagnosis and to first immunosuppressive treatment shortened over time in both groups
Bottom Line
Over 15 years, the French NOMADMUS registry shows shortened time to diagnosis, markedly reduced relapse activity, and a shift toward rituximab and newer biologics in AQP4+NMOSD; rituximab exposure was associated with reduced disability accrual, and MOGAD carried a substantially better long-term disability prognosis than AQP4+NMOSD.
Major Points
- Nationwide French registry of 1,726 patients (769 AQP4+NMOSD, 957 MOGAD) across 98 centers, data extracted June 8, 2024.
- Mean annualized relapse rate declined dramatically from 2010-2014 to 2022-2023: AQP4+NMOSD 0.45 (0.41-0.48) to 0.04 (0.03-0.05); MOGAD 0.35 (0.31-0.39) to 0.10 (0.08-0.12); both p<0.0001.
- Therapeutic shift in AQP4+NMOSD: azathioprine/mycophenolate fell 51.6% to 40.3% while rituximab rose 32.6% to 43.6%, with emergence of new agents (eculizumab, tocilizumab, satralizumab, inebilizumab) reaching 12.5% in 2022-2023.
- Rituximab exposure was associated with lower risk of reaching EDSS 6 in AQP4+NMOSD (HR 0.38; 95% CI 0.21-0.68; p<0.001); older age at onset increased that risk (HR 1.04; p<0.001). Neither factor influenced MOGAD.
- MOGAD had a better disability trajectory than AQP4+NMOSD: EDSS 3 at 5 years 2.8% vs 20%; EDSS 6 at 5 years 0.94% vs 7.4%.
- Methylprednisolone was used in nearly all acute relapses (97.4% AQP4+NMOSD, 97.6% MOGAD); plasma exchange use increased over time, especially in AQP4+NMOSD (28.7% to 54.5%).
- Time from onset to first positive antibody test and to first immunosuppressive treatment shortened over the study period in both groups.
Study Design
- Study Type
- Retrospective nationwide observational registry cohort study
- Randomization
- No
- Blinding
- None (observational registry)
- Sample Size
- 1726
- Follow-up
- Mean 5.1 years overall (AQP4+NMOSD 6.9 y; MOGAD 3.4 y)
- Centers
- 98
- Countries
- France
Primary Outcome
Definition: Change in mean annualized relapse rate (ARR) over time (disease activity)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| AQP4+NMOSD: 0.45 (0.41-0.48) in 2010-2014 to 0.04 (0.03-0.05) in 2022-2023 | MOGAD: 0.35 (0.31-0.39) in 2010-2014 to 0.10 (0.08-0.12) in 2022-2023 | - | <0.0001 |
Limitations & Criticisms
- Retrospective, non-randomized registry design limits causal inference (e.g., rituximab-disability association may reflect confounding by indication or era effects).
- Shorter mean follow-up in MOGAD (3.4 y) than AQP4+NMOSD (6.9 y) may bias disability comparisons.
- Single-country (France) cohort; generalizability to other health systems uncertain.
- Declining ARR over time may partly reflect improved ascertainment, earlier diagnosis, and changing case mix rather than treatment effect alone.
Citation
Roux T, Lejeune FX, Casey R, et al. French NOMADMUS Cohort Overview: Landscape Evolution of AQP4+NMOSD and MOGAD From 2010 to 2024. Neurology. 2026;106(12):e218073. doi:10.1212/WNL.0000000000218073