The effect of rituximab therapy and the risk of hypogammaglobulinamea on immunoglobulin levels in patients with rheumatoid arthritis

Background. Rituximab (RTX) is a biological monoclonal antibody targeting the CD20 antigen on B cells, effectively decreasing disease activity and progression in patients with rheumatoid arthritis (RA). RTX treatment can lead to a decline in plasma cells that produce immunoglobulin, potentially resulting in hypogammaglobulinemia (HGG). This study aims to assess the effect of RTX on immunoglobulin levels and determine the prevalence of HGG in RA patients after receiving different doses and cycles of RTX. Additionally, immunoglobulin levels were compared between patients treated with RTX and those treated with traditional disease-modifying antirheumatic drugs (DMARDs). We also sought to identify patient, disease, and therapy factors associated with HGG to evaluate the importance of monitoring immunoglobulin levels. Method. A single-center observational cross-sectional study was conducted at Baghdad Teaching Hospital between November 2023 and May 2024. Patients with RA were recruited and divided into two groups. The first group consisted of 45 RA patients receiving RTX, and the second group included 45 patients receiving DMARDs. All patients met the American College of Rheumatology (ACR) 1987 or ACR/European League Against Rheumatism (EULAR) 2010 classification criteria for RA. Patients were excluded if they had received RTX for conditions other than RA or if they had been treated with RTX for less than six months. Quantitative IgG and IgA levels were measured via enzyme-linked immunosorbent assay (ELISA) to evaluate the effect of RTX on immunoglobulin levels and compare it with the effect of DMARDs. HGG was defined as an immunoglobulin level below two standard deviations from the mean of age-matched healthy controls. Results. Ninety patients were enrolled in the study, 45 of whom were treated with RTX. The mean number of RTX cycles was 3.67, ranging from 2 to 10 cycles. A significant decrease in immunoglobulin levels was observed post-RTX therapy, with 84.4% of patients exhibiting low IgG levels (<5 μg/ml), leading to HGG. The IgG levels in RTX-treated patients ranged from 4.3 to 22.0 μg/ml, with a mean of 7.28 ± 3.95 μg/ml. In contrast, patients treated with DMARDs maintained normal immunoglobulin levels similar to healthy individuals, with IgG levels ranging from 19.7 to 43.7 μg/ml. RTX also affected IgA levels, but to a lesser extent than IgG. Conclusion. Lower immunoglobulin levels following RTX therapy frequently result in HGG, emphasizing the importance of immunologic surveillance before and after treatment. DMARD therapy did not affect immunoglobulin levels, and concurrent use of DMARDs with RTX offered no protection against HGG. Additionally, HGG was not associated with an increased incidence of infections.