Prevalence and associated factors of secondary hypogammaglobulinemia following rituximab therapy in a real-world cohort

Abstract

Rituximab, an anti-CD20 monoclonal antibody, is widely used in the treatment of autoimmune and hematological diseases. However, its use has been associated with secondary hypogammaglobulinemia (SHG), a condition that may increase susceptibility to infections. The prevalence and clinical factors associated with SHG remain variable and are insufficiently characterized in Latin American populations. To estimate the prevalence of SHG in patients treated with rituximab and identify associated clinical and therapeutic factors. A retrospective, cross-sectional, analytical study was conducted in ISSSTE beneficiaries who received rituximab at the National Medical Center “20 de Noviembre” between 2010 and 2016. Electronic medical records were reviewed to obtain immunoglobulin levels and relevant clinical variables. SHG was defined as decreased serum IgG, IgA, and/or IgM levels below age-adjusted reference values. Bivariate analysis and multivariable logistic regression were performed to identify factors associated with SHG. Among 538 patients treated with rituximab, 133 met inclusion criteria. The cohort was predominantly female (74.4%) with a mean age of 53 years. The most frequent diagnoses were rheumatoid arthritis (39.1%), systemic lupus erythematosus (21.8%), and non-Hodgkin lymphoma (13.5%). SHG was identified in 42.9% of patients, with IgG being the most frequently affected isotype. In bivariate analysis, male sex, pre-existing hypogammaglobulinemia, and concomitant use of cytotoxic immunosuppressive agents were associated with SHG. However, no independent predictors were identified in multivariable logistic regression models. SHG was frequently identified in patients treated with rituximab in this real-world cohort. Although independent predictors were not identified in multivariable analysis, baseline immunoglobulin levels and concomitant immunosuppressive therapy have been proposed as potential risk factors in previous studies and warrant careful clinical consideration. These findings support the importance of baseline and longitudinal immunoglobulin monitoring in patients receiving B cell–targeted therapies. Prospective longitudinal studies are needed to better characterize the clinical impact and optimal monitoring strategies for rituximab-associated SHG.