Real-World Efficacy and Safety of Neuromyelitis Optica Spectrum Disorder Disease-Modifying Treatments

Neuromyelitis optica spectrum disorder (NMOSD) is characterized by inflammatory relapses that result in severe disability, including blindness and paralysis. Relapse prevention with safe and effective treatments is key to reducing long-term disability. We aim to compare the efficacy and safety of rituximab-the most commonly used treatment-with recently approved NMOSD-specific treatments-eculizumab, inebilizumab, satralizumab-and other common off-label NMOSD treatments-mycophenolate mofetil (MMF) and azathioprine. The primary outcomes are relapse-free survival and annualized relapse rate. Secondary outcomes are serious infectious adverse event (SIAE) and treatment-limiting adverse event (TLAE)-free survival.

A retrospective cohort study of NMOSD was conducted on patients at the Mass General Brigham hospital network. Patients meeting 2015 NMOSD diagnostic criteria, who were seen between 2000 and 2024 were included. Poisson regression, frequentist negative binomial analysis with inverse probability of treatment weighting, and Cox proportional hazard models were used to assess relapse rates, relapse-free survival, and SIAEs.

A total of 176 patients with NMOSD were followed for a median of 9 years (interquartile range: 5-14), contributing 691 relapse assessments. The median age at first attack was 42 years, and 83% were female. Compared with rituximab, relapse risk was significantly lower with C5 inhibitors (HR 0.12, 95% CI 0.07-0.24), inebilizumab (HR 0.22, 95% CI 0.12-0.65), and satralizumab (HR 0.19, 95% CI 0.11-0.42). Annualized relapse rates were the lowest for C5 inhibitors (0, 95% CI 0-0.063) and the highest for azathioprine (0.34, 95% CI 0.18-0.56). A composite outcome of relapse, SIAE, and TLAE favored C5 inhibitors (HR 0.22, 95% CI 0.05-0.67), while azathioprine (HR 2.33, 95% CI 1.08-4.86) and MMF (HR 1.75, 95% CI 1.02-2.95) showed increased risk compared with rituximab. C5 inhibitors had the lowest incidence of serious infections (incidence rate ratio 0.16, 95% CI 0.05-0.42 vs rituximab).

Clinicians should consider using NMOSD-approved treatments given their favorable efficacy and safety profiles in the real-world setting. MMF and azathioprine should be avoided. We caution against rituximab as a default first-line given the cumulative risk of relapse, SIAEs, and TLAEs over time.

This study provides Class III evidence that, in patients with NMOSD, FDA-approved disease-modifying therapies are associated with lower relapse rates and fewer serious adverse events compared with rituximab.