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.