Rituximab-associated hypogammaglobulinemia: Incidence, predictors and outcomes in patients with multi-system autoimmune disease

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.