Rituximab-associated Hypogammaglobulinemia in pediatric patients with autoimmune diseases

Abstract

Background Despite the increased use of rituximab in treating pediatric patients with autoimmune diseases in the last decade, there are limited data on rituximab safety in those subjects who have a developing immune system. The objective of this study is to determine the prevalence of hypogammaglobulinemia in children with autoimmune disease receiving rituximab within the first three years of treatment in the pediatric rheumatology clinic at a tertiary care center. Methods We conducted a retrospective chart review of 63 pediatric subjects who received rituximab for the treatment of their autoimmune disease. Immunoglobulin gamma (IgG) levels, immunosuppressive medication and the need for immunoglobulin replacement therapy were evaluated. Hypogammaglobulinemia was defined as a serum IgG level less than two standard deviations below the mean for age-matched healthy controls. Results Twenty-eight patients (44%) were found to have hypogammaglobulinemia. Hypogammaglobulinemia occurred within the first six months of rituximab treatment in the majority of patients (22 out of 28). The occurrence of hypogammaglobulinemia varied based on the rituximab indication: 46% pediatric Systemic Lupus Erythematosus (SLE), 71% autoimmune CNS disease, 60% ANCA vasculitis, and 12% in the miscellaneous group. Autoimmune CNS disease had more severe hypogammaglobulinemia, more persistent and was associated with more frequent or severe infections. Three patients with autoimmune CNS disease and one with SLE were given IgG replacement therapy to prevent recurrent or severe infections. Conclusions The prevalence of hypogammaglobulinemia in rituximab treated children with autoimmune disease seems to be higher than published data for adults, especially for children with autoimmune CNS disease. The onset of hypogammaglobulinemia is usually within six months of initiation of rituximab therapy. We recommend: 1) obtaining an IgG level prior to starting rituximab; 2) close monitoring for hypogammaglobulinemia after the use of rituximab in pediatric patients and 3) early institution of immunoglobulin replacement therapy if patients develop recurrent infections.

Autoimmune cytopenias following allogeneic hematopoietic stem cell transplant in pediatric patients: Response to therapy and late effects

“…Short-and long-term effects of the most frequently used AIC treatments (steroids and rituximab) and supportive care measures (transfusions) are well established in various populations. 12,[34][35][36][37] Comparing our AIC cohort to controls, we found that iron overload and steroid-induced late effects including AVN and cataracts were more prevalent. This is likely attributed to the higher need of transfusion support leading to iron overload and prolonged courses of steroids to treat these AICs.…”

Juvenile Dermatomyositis: New Clues to Diagnosis and Therapy

“…Another problem is that the use of TNF inhibitors to treat other rheumatic diseases, such as psoriatic arthritis, has precipitated the development of JDM [135], as well as inflammatory myopathies in adults [136,137]. immunoglobulin G (IgG) levels is advisable, especially in the first year of therapy, for there is a 30-50% prevalence of hypogammaglobulinemia; some patients require an immunoglobulin replacement therapy [138]. Rituximab has been used successfully to treat JDM patients who failed first-line therapy [139,140], [141].…”

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