Rituximab-Induced Hypogammaglobulinemia and Infections in AQP4 and MOG Antibody-Associated Diseases

Abstract

Objective: To determine the potential association between infections and rituximab (RTX)-induced hypogammaglobulinemia among patients with CNS inflammatory diseases.

Methods: We included in a prospective observational study all consecutive adults with aquaporin 4 (AQP4) or myelin oligodendrocyte glycoprotein (MOG) antibody-positive disorders treated with RTX. Dosing schedule was adapted to memory B-cell measurement.

Results: We included 48 patients (mean age 47 [SD: 14] years; 77% females; 31 AQP4 positive and 17 MOG positive). The median follow-up was 3.6 years (range: 0.9-8.1 years). The median number of RTX infusions was 8 (range: 2-14). The median dosing interval was 6 months (range: 1.7-13.7 months). Sixty-seven symptomatic infections (SIs) were observed in 26 of 48 (54%) patients, including 13 severe infections in 9 (19%). Urinary and lower respiratory tract infections were the most frequent, representing 42% and 21% of SI. At RTX onset, the immunoglobulin G (IgG) level was abnormal in 3 of 48 (6%) patients. After RTX, 15 (31%), 11 (23%), 3 (6%), and 0 of 48 patients showed sustained IgG level <7, <6, <4, and <2 g/L, respectively. On multivariate Cox proportional hazards analysis, the main variables explaining the risk of SI were the presence of urinary tract dysfunction (hazard ratio [HR] = 34, 95% CI 4-262, p < 0.001), the dosing intervals (HR = 0.98, 95% CI 0.97-0.99, p < 0.001), and the interaction between IgG level and urinary tract dysfunction (HR = 0.67, 95% CI 0.53-0.85, p < 0.005). IgG level <6 g/L during RTX was associated with male sex (HR = 4, 95% CI 1.4-11.4, p < 0.01) and previous immunosuppression (HR = 3.4, 95% CI 1.2-10, p < 0.05).

Conclusions: RTX used as maintenance therapy in CNS inflammatory diseases is frequently associated with reduced IgG level and increases the infection risk of the most vulnerable patients.