Age, Low Immunoglobulin G, and M Serum Levels Predict Infections in People With AQP4 ‐ IgG + NMOSD Treated With Rituximab—A Multicenter Cohort Study From the German Neuromyelitis Optica Study Group ( NEMOS )

Introduction Rituximab is effective and widely used as long‐term treatment in aquaporin‐4‐IgG‐positive neuromyelitis optica spectrum disorder (AQP4‐IgG+ NMOSD). However, infections remain a significant concern during rituximab treatment. Methods We conducted a retrospective multicenter cohort study within the NMO Study Group (NEMOS) in Germany, analyzing demographic and clinical data from people with AQP4‐IgG+ NMOSD receiving rituximab or azathioprine by retrospective chart, and compared infection occurrence and severity. For rituximab‐treated patients, we collected laboratory data (blood lymphocytes, B‐cell counts, serum IgG, IgM, and IgA levels), assessed risk factors for infections, and determined the probability of infection within a 3‐month window before and after the laboratory assessment. Results In 92/170 rituximab and in 12/33 azathioprine treatment episodes, one or more infections were documented. Rituximab and azathioprine showed comparable types and risk of infection (HR = 1.24, 95% CI: 0.68–2.25). Rituximab‐treated individuals older than 60 years had a higher risk of infection (HR = 1.62, 95% CI: 1.02–2.57). Hypogammaglobulinemia (IgG < 6.0 g/L: OR = 2.27, 95% CI: 1.15–4.48; IgM < 0.3 g/L: OR = 2.08, 95% CI: 1.05–4.09) predicted infections and the occurrence of both low IgG and IgM serum levels further increased the risk of infection (OR = 2.77, 95% CI: 1.10–6.98) during rituximab treatment. Low IgG and IgA serum levels as well as lymphopenia predicted infection‐related hospitalizations. Conclusion Age > 60 years and immunoglobulin serum levels during rituximab treatment may serve as predictors for infection and help to individualize treatment decisions in NMOSD.