Abstract
ObjectiveTo evaluate the characteristics of patients with autoimmune disease with hypogammaglobulinemia following rituximab (RTX) and describe their long-term outcomes, including those who commenced immunoglobulin replacement therapy.MethodsPatients received RTX for autoimmune disease between 2003 and 2012 with immunoglobulin G (IgG) <7g/L were included in this retrospective series. Hypogammaglobulinemia was classified by nadir IgG subgroups of 5 to <7g/L (mild), 3 to <5g/L (moderate) and <3g/L (severe). Characteristics of patients were compared across subgroups and examined for factors associated with greater likelihood of long term hypogammaglobulinemia or immunoglobulin replacement.Results142 patients were included; 101 (71%) had anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis (AAV), 18 (13%) systemic lupus erythematosus (SLE) and 23 (16%) other conditions. Mean follow-up was 97.2 months from first RTX. Hypogammaglobulinemia continued to be identified during long-term follow-up. Median time to IgG <5g/L was 22.5 months. Greater likelihood of moderate hypogammaglobulinemia (IgG <5g/L) and/or use of immunoglobulin replacement therapy at 60 months was observed in patients with prior cyclophosphamide exposure (odds ratio (OR) 3.60 [95% confidence interval (CI) 1.03 – 12.53], glucocorticoid use at 12 months [OR 7.48 (95% CI 1.28 – 43.55], lower nadir IgG within 12 months of RTX commencement [OR 0.68 (95% CI 0.51 – 0.90)] and female sex [OR 8.57 (95% CI 2.07 – 35.43)]. Immunoglobulin replacement was commenced in 29/142 (20%) and associated with reduction in infection rates, but not severe infection rates.ConclusionHypogammaglobulinemia continues to occur in long-term follow-up post-RTX. In patients with recurrent infections, immunoglobulin replacement reduced rates of non-severe infections.
Highlights
B cell depletion plays a key role in the management of many autoimmune diseases
Characteristics of patients were compared across subgroups and examined for factors associated with greater likelihood of long term hypogammaglobulinemia or immunoglobulin replacement
Greater likelihood of moderate hypogammaglobulinemia (IgG
Summary
B cell depletion plays a key role in the management of many autoimmune diseases. Rituximab (RTX) is licensed for use in rheumatoid arthritis (RA) and AAV, and clinical trials have evaluated RTX in other autoimmune conditions including SLE. Despite limited evidence of hypogammaglobulinemia in patients receiving RTX in these studies, it has been consistently identified in observational studies of patients with autoimmune disease [1,2,3,4,5,6,7]. Lower baseline immunoglobulin G (IgG) levels, including levels within population norms, have been associated with subsequent hypogammaglobulinemia [2, 4, 6, 7]. An association between cumulative RTX exposure and hypogammaglobulinemia has not been demonstrated [2,3,4, 7]. Extrapolated from the treatment of patients with common variable immunodeficiency (CVID), prophylactic antibiotics and immunoglobulin replacement therapy are considered where there is a combination of hypogammaglobulinemia, poor vaccination responses, and recurrent and/or severe infection
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