Uncovering Infections in NMOSD: A U.S. Real-world Comparison Between Broad Immunosuppressants and Targeted Immunotherapy

Objective This study compares frequency of infection among patients with neuromyelitis optica spectrum disorder (NMOSD) receiving azathioprine, mycophenolate, rituximab, inebilizumab, satralizumab, or ravulizumab. Background MOSD causes debilitating relapses which can result in severe disability. Long-term treatment with immunomodulatory therapies is required to prevent relapses and disability accrual. Several newer FDA-approved biologic therapies are increasingly used, though treatment with longer standing non-FDA approved therapies remains common. Long-term data on real-world infection risk are limited, which makes evidence-based treatment selection challenging for clinicians. Design/Methods This retrospective cohort study used CHRONOS hybrid claims data ecosystem to identify adult patients with NMOSD between January 2017 and December 2025. Patients were followed for at least 1 year from first NMOSD treatment and classified into treatment groups of azathioprine, mycophenolate, rituximab, inebilizumab, satralizumab, or ravulizumab. Infection rates were estimated using generalized estimating equations to calculate infection incidence rate ratio (IRR) versus ravulizumab, adjusted for variable treatment duration, age, sex, prior B-cell therapy duration, Charlson comorbidity index, and history of transverse myelitis. Results A total of 5,391 patients with NMOSD were treated with at least one of azathioprine (n=507), mycophenolate (n=992), rituximab (n=3460), inebilizumab (n=603), satralizumab (n=344), or ravulizumab (n=215) during their follow-up for 6,121 unique patient treatment periods after accounting for treatment switches. Compared to ravulizumab, azathioprine demonstrated the highest relative infection rate (IRR 1.94, 95% CI 1.52-2.47, p<0.001), followed by mycophenolate (IRR 1.80, 95% CI 1.46-2.23, p<0.001), rituximab (IRR 1.73, 95% CI 1.41-2.11, p<0.001), satralizumab (IRR 1.60, 95% CI 1.23-2.07, p<0.001), and inebilizumab (IRR 1.31, 95% CI 1.05-1.64, p=0.019). Conclusions This real-world study demonstrated higher infection rates in broader immunosuppressive therapies used for long-term treatment in patients with NMOSD relative to a more targeted FDA-approved complement inhibitor, ravulizumab. These findings may help inform clinical decision making for those who take care of patients living with NMOSD.