Rituximab Associated Hypogammaglobulinemia in Autoimmune Disease

Objective To 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. Methods Patients 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. Results 142 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. Conclusion Hypogammaglobulinemia continues to occur in long-term follow-up post-RTX. In patients with recurrent infections, immunoglobulin replacement reduced rates of non-severe infections.