OBJECTIVES: Rituximab has become the cornerstone of induction treatment in ANCA-associated vasculitis (AAV). B-cell depletion may increase the risk of hypogammaglobulinemia, potentially leading to severe infections. This study aims to assess factors associated with hypogammaglobulinemia in AAV patients treated with rituximab. METHODS: This retrospective cohort study included AAV patients treated with rituximab induction in 14 European centres. Severe adverse events (SAEs) were defined as episodes requiring hospitalization or intravenous antibiotics, malignancies, or death. Linear and logistic regression were used to identify predictors of IgG levels and of the risk of hypogammaglobulinemia, defined as IgG ≤7 g/l at 6 months. RESULTS: The study included 227 patients. IgG levels at 6 months were lower than baseline (P < 0.001). Patients requiring intravenous antibiotics during the first 6 months had lower IgG levels at 6 months (P = 0.004). Age [β (95% CI): -0.23 (-0.38, -0.08) per 10 years, P = 0.003], oral glucocorticoid dose at induction [β (95% CI): -0.37 (-0.51, -0.24) per sqrt-transformed mg prednisone, P < 0.001] and concomitant use of intravenous glucocorticoid pulses [β (95% CI): -0.88 (-1.73, -0.02), P = 0.044] were associated with IgG levels at 6 months. Hypogammaglobulinemia was identified in 97 (42.7%) patients. In multivariable logistic regression, factors associated with the risk of hypogammaglobulinemia were age [OR (95% CI): 1.46 (1.15, 1.86) per 10 years, P = 0.002] and oral glucocorticoid dose at induction [OR (95% CI): 1.52 (1.23, 1.89) per 10 mg prednisone, P < 0.001]. CONCLUSIONS: In AAV patients treated with rituximab, hypogammaglobulinemia at 6 months after induction is common, and lower IgG levels are associated with serious infections. The risk of hypogammaglobulinemia in these patients increases with age and higher glucocorticoid doses.

Clinical Sciences in Lund Lund University Lund Sweden

Department of Autoimmune Diseases Hospital Clinic de Barcelona University of Barcelona Institut d'Investigacions Biomèdiques August Pi i Sunyer Barcelona Spain

Department of Biomedical Experimental and Clinical Sciences Mario Serio University of Firenze Firenze Italy; Nephrology and Dialysis Unit Department of Pediatrics Meyer Children's Hospital Firenze Italy

Department of Health Medicine and Caring Sciences Linköping University Linköping Sweden

Department of Medicine and Surgery Università degli Studi di Milano Bicocca and ASST Monza Milano Italy

Department of Medicine Division of Rheumatology Karolinska Institutet Solna and Rheumatology Karolinska University Hospital Stockholm Sweden

Department of Medicine University of Cambridge Cambridge UK

Department of Nephrology 1st Faculty of Medicine General University Hospital Charles University Prague Czech Republic

Department of Nephrology University of Birmingham Birmingham UK

Department of Rheumatology Lupus and Vasculitis Clinic Copenhagen University Hospital Rigshospitalet Denmark

Division of Nephrology and Dialysis and Department of Medical and Surgical Specialties Radiological Sciences and Public Health ASST Spedali Civili and University of Brescia Brescia Italy

Division of Renal Medicine CLINTEC Karolinska Institutet Stockholm Sweden

Nephrology and Dialysis Unit Department of Biomedical and Clinical Sciences Università di Milano and ASST Fatebenefratelli Sacco Milano Italy

Renal Division ASST Santi Paolo e Carlo Università degli Studi di Milano Milano Italy

Rheumazentrum Schleswig Holstein Mitte Neumünster Germany

References provided by Crossref.org

Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial