Immunoglobulin replacement therapy in antineutrophil cytoplasmic antibody-associated vasculitis with rituximab-associated hypogammaglobulinemia: infection outcomes and disease course in a retrospective cohort.

OBJECTIVE: To evaluate whether immunoglobulin replacement therapy (IgR), initiated for infection prophylaxis in patients with ANCA-associated vasculitis (AAV) receiving rituximab, is associated with changes in infection burden, disease activity, and the ability to de-escalate immunosuppression. METHODS: We performed a retrospective single-center study of 16 patients with AAV treated with rituximab who developed secondary hypogammaglobulinemia (IgG <600 mg/dL) and subsequently received IgR between 2014 and 2024. Patients receiving IgR for primary immunodeficiency were excluded. Data collected included demographics, ANCA serotype, relapse history, infection burden, immunosuppressive regimen, and serum IgG levels before and after IgR. Primary outcomes were infections and disease relapse before versus after IgR initiation. Secondary outcomes included changes in serum IgG and rituximab use. RESULTS: Prior to IgR, mean IgG was 287 ± 98 mg/dL, 14/14 patients tested had impaired vaccine responses, and 13/16 (81%) experienced recurrent or severe infections. Seven patients (44%) had at least one disease relapse while on rituximab maintenance. After IgR, mean IgG increased to 1018 ± 234 mg/dL, with normalization in 14/15 (93%). Recurrent or severe infections decreased to 1/16 (6%). Following IgR initiation, no disease relapses were observed during a median follow-up of 29.0 months (IQR 14.5-61.4; range 2.8-127.8), despite rituximab discontinuation in 10 patients and dose-interval extension in the remaining 6 patients. IgR was discontinued in 3 patients without relapse. CONCLUSION: In this cohort of AAV patients with rituximab-associated hypogammaglobulinemia, IgR demonstrated improved immunoglobulin levels and reduced infection burden and was associated with sustained disease remission despite immunosuppression de-escalation. Further studies are needed to determine whether IgR influences disease activity in AAV.