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

Abstract Objective Despite the increasing use of rituximab in 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 to better tailor 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 MPA (75%), MPO-ANCA positive (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 eGFR (HR [95% CI]: 1.84 [1.13–2.98] per 30 ml/min/1.73m2 eGFR) and female sex (HR [95% CI]: 2.70 [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.