To evaluate the risk of developing hypogammaglobulinemia and the associated risk of infections in patients with multiple sclerosis (MS) treated with rituximab through a systematic review and meta-analysis.

Multiple sclerosis (MS) is a chronic autoimmune disease causing degradation of myelin in the central nervous system, leading to neurological symptoms and disability. Rituximab, a monoclonal antibody that targets B cells, is effective in treating MS but carries risks of immunosuppression, such as hypogammaglobulinemia (low immunoglobulin levels) and infections.

A search of PubMed, Embase, and Web of Science was conducted to identify studies assessing the risk of hypogammaglobulinemia and infections in MS patients treated with rituximab. Randomized controlled trials (RCTs), observational longitudinal, and cross-sectional studies were included. Data were extracted and analyzed using R software 4.3.1 for meta-analysis to synthesize the results and assess the association between rituximab use and the risks.

Twenty-one studies met inclusion criteria, with a combined sample of 21,175 patients treated with rituximab. Studies showed a 9% prevalence of hypogammaglobulinemia in 11,301 patients (95% CI [0.06 - 0.11]). Severe infections occurred in 6% of 16,803 patients (95% CI [0.03 - 0.14]). The hazard ratio (HR) for severe infections was 1.0070 (95% CI [0.69 - 1.46]), indicating no significant increase in risk. In outpatients, the HR was 1.24 (95% CI [0.65 - 2.36]), also not statistically significant.

Rituximab use in MS is associated with a significantly increased risk of hypogammaglobulinemia but no conclusively increase the risk of severe infections. Regular monitoring of immunoglobulin levels and clinical evaluations remain important for managing hypogammaglobulinemia. Long-term immunological follow-up is recommended to ensure safety during rituximab therapy.