Background/Purpose: Rituximab is an anti-CD20 monoclonal antibody increasingly used in immunologic and malignant conditions to deplete B cells. Suppression of humoral immunity after rituximab exposure may last for months or years and may increase the risk of bacterial and viral infections. The aims of this study were to characterize changes in immunoglobulin G (IgG) concentrations after rituximab exposure and determine the relation between low IgG concentrations and serious infections requiring hospitalization in children with rheumatic diseases.

Methods: This retrospective cohort study included patients in the Division of Rheumatology at our institution receiving at least one dose of rituximab therapy from 2002-2012 at our institution. Medication exposure, IgG levels, and infections requiring hospitalizations were recorded.

Results: We identified 101 patients (74% female) who received 174 rituximab courses. The median age was 15.2 years (range: 2.5-19.7 years) at initiation of rituximab therapy. More than one rituximab course was given in 41 patients with a maximum of 8 courses. The most common indications for rituximab were systemic lupus erythematosus and related conditions (n=60), inflammatory myopathies (n=17), and granulomatosis with polyangiitis (n=9). Of the 53 with baseline IgG measurements not receiving concurrent IVIG, IgG decreased by a median of 252 mg/dL (p<0.001) over a median of 0.63 years. IgG continued to be lower than baseline by a median of 190 mg/dL (p<0.001) at the last documented follow up, which was after a median of 1.5 years. Of the 51 with baseline IgG greater than 600 mg/dL, new-onset hypogammaglobulinemia was noted in five (range 307-560 mg/dL). Two patients had baseline and post-exposure IgG levels less than 600 mg/dL. In the 247.2 person years of follow up, there was a total of 31 hospitalizations for infection in 18 patients (12.5 infections per 100 person-years; 95% CI 8.1 to 16.9). The median time to first infection was 1.1 years (range: 0.1-4.2). Exposure to cyclophosphamide or more than one course of rituximab was not associated with a greater infection risk. However, IgG levels less than 400 mg/dL were associated with greater odds of infection (OR 5.7, 95% CI 1.1-28.8). Two of three patients who died of infectious complications had IgG levels less than 400 mg/dL.

Conclusion: IgG levels decreased after exposure to rituximab, but significantly low IgG levels at follow up were uncommon, particularly if levels were normal at baseline. However, infections requiring hospitalization were common in this study population. Infection rates at our institution were similar to published infection rates in clinical trials. Significant hypogammaglobulinemia was associated with a greater risk of infection and was present in two of the three children who died of infectious complications. Future research is required to define predictors of infection in rituximab recipients and strategies to reduce infection risk are urgently needed.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immunologic-monitoring-and-infectious-complications-in-pediatric-rheumatology-patients-treated-with-rituximab/