Sustained post-rituximab B-cell depletion is common in ANCA-associated vasculitis and is affected by sex and renal function

Author:

Mescia Federica12ORCID,Salviani Chiara2,Tonoli Mattia2,Affatato Stefania2,Moratto Daniele3,Tedesco Martina12,Guerini Alice12,Gemmo Alessia12,Camoni Marta12,Delbarba Elisa2,Zubani Roberto12,Garrafa Emirena45,Chiarini Marco3,Gregorini Gina6,Scolari Francesco12,Alberici Federico12ORCID

Affiliation:

1. Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia , Brescia , Italy

2. Nephrology Unit, Spedali Civili Hospital , ASST Spedali Civili of Brescia, Brescia , Italy

3. Flow Cytometry Laboratory, Department of Laboratory Diagnostics , ASST Spedali Civili di Brescia, Brescia , Italy

4. Department of Clinical and Experimental Sciences, University of Brescia , Brescia , Italy

5. Department of Laboratory Diagnostics , ASST Spedali Civili, Brescia , Italy

6. Independent Researcher , Brescia , Italy

Abstract

ABSTRACT Objective Despite the increasing use of rituximab in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), it remains unclear what the optimal dosing is, especially for maintenance of remission. A deeper understanding of post-rituximab B-cell repopulation patterns may aid better-tailored treatment. Methods This is a monocentric, retrospective study including ANCA-positive AAV patients receiving a single course of rituximab induction. CD19+ B cells were longitudinally monitored with flow cytometry. B-cell repopulation was defined as CD19+ >10 cells/μL. Results Seventy-one patients were included, the majority with microscopic polyangiitis (75%), myeloperoxidase-ANCA positivity (75%) and with renal involvement (79%). During a median follow-up of 54 months since the first rituximab infusion, 44 patients (62%) repopulated B cells, with a median time to repopulation of 39 months (range 7–102). Patients experiencing B-cell depletion lasting longer than the overall median time to repopulation (39 months) exhibited a lower risk of flare and higher risk of serious infection. In multivariate Cox regression, higher estimated glomerular filtration rate (eGFR) [hazard ratio (HR) 1.84, 95% confidence interval (CI) 1.13–2.98 per 30 mL/min/1.73 m2 eGFR] and female sex (HR 2.70, 95% CI 1.37–5.31) were independent predictors of increased rate of B-cell repopulation. Conclusion A subset of AAV patients develop sustained post-rituximab B-cell depletion, which associates with reduced risk of flare and increased risk of serious infection in the long term. Preserved renal function and female sex are associated with faster B-cell repopulation. These observations further highlight the need to personalize immunosuppression to improve clinical outcomes.

Publisher

Oxford University Press (OUP)

Subject

Transplantation,Nephrology

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4. Long-term outcomes and prognostic factors for survival of patients with ANCA-associated vasculitis;Sánchez Álamo,2023

5. KDIGO 2021 clinical practice guideline for the management of glomerular diseases;Rovin;Kidney Int,2021

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