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The anti-CD20 B cell depleting monoclonal antibody rituximab is being used increasingly for autoimmune diseases, including patients with refractory disease with extensive prior exposure to immunosuppressive treatments. Rituximab, in this context, may be associated with increased risk of adverse effects, in particular hypogammaglobulinemia which predisposes to recurrent infections necessitating Immunoglobulin G replacement. Outcome data following Immunoglobulin G replacement after rituximab in patients with autoimmune disease are limited. We conducted a retrospective study in a tertiary referral lupus and vasculitis clinic of 288 patients who received rituximab. Clinical details of patients prescribed IgG replacement therapy following rituximab treatment were reviewed. We identified 12 patients with autoimmune disease, 10/12 with systemic vasculitis, received IgG replacement for the treatment of recurrent infections in the context of persistent moderate or severe hypogammaglobulinemia following rituximab. We observed a range of ages (16-67 years), rituximab dosages (2-15.8 g), previous immunosuppression (median 3.5 non-glucocorticoid agents) and duration of disease (2-228 months). Six continued to receive rituximab alongside IgG replacement therapy to maintain disease control. IgG replacement appeared to decrease the incidence and severity of infections, and recovery of IgG concentrations allowed cessation of IgG replacement in two patients after 4 and 7.5 years of treatment. IgG monitoring is useful for patients receiving rituximab. IgG replacement for sustained hypogammaglobulinemia with recurrent infections appeared to be useful in this series. The IgG replacement course is prolonged in most patients, but IgG recovery is reported., (Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.)

Rituximab is a B cell depleting monoclonal antibody used to treat lymphoma and autoimmune disease. Hypogammaglobulinemia has occurred after rituximab for lymphoma and rheumatoid arthritis but data are scarce for other autoimmune indications. This study describes the incidence and severity of hypogammaglobulinemia in patients receiving rituximab for small vessel vasculitis and other multi-system autoimmune diseases. Predictors for and clinical outcomes of hypogammaglobulinemia were explored. We conducted a retrospective study in a tertiary referral specialist clinic. The severity of hypogammaglobulinemia was categorized by the nadir serum IgG concentration measured during clinical care. We identified 288 patients who received rituximab; 243 were eligible for inclusion with median follow up of 42 months. 26% were IgG hypogammaglobulinemic at the time that rituximab was initiated and 56% had IgG hypogammaglobulinemia during follow-up (5-6.9 g/L in 30%, 3-4.9 g/L in 22% and <3 g/L in 4%); IgM ≤0.3 g/L in 58%. The nadir IgG was non-sustained in 50% of cases with moderate/severe hypogammaglobulinemia. A weak association was noted between prior cyclophosphamide exposure and nadir IgG concentration, but not cumulative rituximab dose. IgG concentrations prior to and at the time of rituximab correlated with the nadir IgG post rituximab. IgG replacement was initiated because of recurrent infection in 12 (4.2%) patients and a lower IgG increased the odds ratio of receiving IgG replacement. Rituximab is associated with an increased risk of hypogammaglobulinemia but recovery of IgG level can occur. IgG monitoring may be useful for patients receiving rituximab., (Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.)