Background/Purpose: Rituximab (RTX) is the standard of care for both induction and maintenance in ANCA-associated vasculitides (AAVs). While CD19 B-cell monitoring is used to evaluate the duration and magnitude of the biological effect of RTX, its prognostic value in predicting relapse remains controversial. We aimed to determine the significance of incomplete B-cell depletion during maintenance therapy in AAV patients and its subsequent risk of relapse.

Methods: This is a retrospective, single-center cohort study on AAV patients including patients with the following inclusion criteria: i) newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis, ii) induction therapy with either cyclophosphamide (CYC) or RTX, iii) standard maintenance therapy with RTX 500 mg fixed dose every 6 months. Follow-up started from the first maintenance treatment (month 0) until the earliest occurrence of flare, last follow-up, or death. CD19 levels were measured at each RTX infusion and analyzed as a time-dependent variable. We analyzed the risk of relapse separately in 2 phases: during RTX maintenance treatment (from the first RTX infusion until 6 months after the last infusion), and after RTX discontinuation (from 6 months after the last RTX infusion until last follow-up).

Results: 199 patients were included. The median duration of RTX maintenance was 19 (IQR 18-40) months. A total of 21 relapses were observed during maintenance, and 30 after discontinuation of RTX. At month 0, incomplete B-cell depletion, either defined for CD19 >1/mm3 or >5/mm3 were observed in 29% and 18.1% of patients, respectively, and remained stable during maintenance treatment. Variables that were associated with the magnitude of B-cell depletion during RTX maintenance therapy, evaluated by the area under the curve (AUC) of CD19+ B cells, were the age at diagnosis (β = -0.05; 95% CI: -0.11 to 0.00) and serum creatinine level (β = 0.01; 95% CI: 0.00 to 0.02).During maintenance therapy, age was the only variable associated with the risk of relapse (OR 0.97, 95%CI 0.94-1.00, p=0.019), while B cell count, whatever the definition used, was not associated with relapse during maintenance. In multivariate analysis, age remained associated with the risk of relapse (HR 0.97, 95%CI 0.94-1.00, p=0.019).After RTX discontinuation, variables that was associated with the risk of relapse were absolute CD19+ B cell count (HR 1.01, 95%CI 1.00-1.01, p=0.024), CD19+ B cell ≤5/mm3 (HR 0.44, 95%CI 0.21-0.95, p=0.036) at last RTX infusion, and the AUC of CD19+ B cells during maintenance (HR 1.01, 95%CI 1.00-1.03, p=0.040). In multivariate analysis, all these variables related to B-cell depletion remained associated with the subsequent risk of relapse.

Conclusion: Incomplete B-cell depletion during RTX maintenance, which occurs in one third of patients, is not associated with an increased risk of relapse while RTX is continued. In contrast, after discontinuation of RTX, the B-cell count at the last RTX infusion or the AUC of CD19+ B cells during maintenance were associated with subsequent relapse risk, suggesting that achieving complete B-cell depletion may be a goal to reduce the risk of subsequent relapse.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-impact-of-incomplete-b-cell-depletion-in-anca-associated-vasculitis-patients-receiving-maintenance-rituximab-therapy-a-retrospective-study/