Comparative Efficacy of DMT in NMOSD
(2026)Objective
To compare real-world efficacy of all major NMOSD disease-modifying therapies using rituximab as the reference standard
Study Summary
• C5 inhibitors were most effective (HR 0.12–0.19 vs rituximab), while azathioprine (HR 2.33) and MMF (HR 1.75) performed significantly worse.
• First head-to-head real-world comparison of all major NMOSD therapies.
• First head-to-head real-world comparison of all major NMOSD therapies.
Intervention
Observational comparison of C5 inhibitors, inebilizumab, satralizumab, tocilizumab, rituximab, azathioprine, MMF
Inclusion Criteria
AQP4-seropositive NMOSD from multiple centers with documented DMT treatment
Study Design
Arms: C5 inhibitors (eculizumab/ravulizumab),Inebilizumab,Satralizumab,Tocilizumab,Rituximab (reference),Azathioprine,MMF
Patients per Arm: 176 total, multiple treatment exposures per patient
Outcome
C5 inhibitors HR 0.12–0.19, inebilizumab HR 0.22, satralizumab HR 0.19 vs rituximab (all superior). Azathioprine HR 2.33, MMF HR 1.75 (both worse than rituximab). Tocilizumab comparable.
Bottom Line
C5 inhibitors were most effective (HR 0.12–0.19 vs rituximab), while azathioprine (HR 2.33) and MMF (HR 1.75) performed significantly worse. First head-to-head real-world comparison of all major NMOSD therapies.
Major Points
- First real-world head-to-head comparison of all major NMOSD therapies: C5 inhibitors, inebilizumab, satralizumab, tocilizumab, rituximab, azathioprine, MMF.
- Clear efficacy hierarchy: C5 inhibitors (HR 0.12–0.19) > inebilizumab (HR 0.22) ≈ satralizumab (HR 0.19) > rituximab (reference) ≈ tocilizumab >> azathioprine (HR 2.33) > MMF (HR 1.75).
- Traditional immunosuppressants (azathioprine, MMF) performed significantly WORSE than rituximab — should be considered suboptimal.
- 176 AQP4-seropositive patients with median 9-year follow-up provides substantial real-world evidence.
- Results consistent with Phase 3 RCT data for individual agents, strengthening confidence in the findings.
- Supports early use of targeted biologics over traditional immunosuppressants in AQP4+ NMOSD.
Study Design
- Study Type
- Retrospective multicenter cohort study
- Sample Size
- 176
Limitations & Criticisms
- Retrospective observational design — channeling bias and indication bias are inherent limitations
- Patients on C5 inhibitors likely had more severe/refractory disease (yet still had best outcomes), which may actually underestimate efficacy
- Treatment durations varied — some drugs had shorter exposure periods
- AQP4+ only — results may not apply to seronegative NMOSD
- Exact patient numbers per DMT not specified in abstract — some treatment groups may be small