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Abstract: TH-PO508

Kinetics of B Cell Repopulation After Rituximab in ANCA-Associated Vasculitis: Clinical Significance and Predictive Factors

Session Information

Category: Glomerular Diseases

  • 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials

Authors

  • Mescia, Federica, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy
  • Salviani, Chiara, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy
  • Affatato, Stefania, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy
  • Tonoli, Mattia, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy
  • Guerini, Alice, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy
  • Tedesco, Martina, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy
  • Moratto, Daniele, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy
  • Gregorini, Gina Alessandra, Independent researcher, Brescia, Italy
  • Chiarini, Marco, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy
  • Scolari, Francesco, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy
  • Alberici, Federico, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy
Background

Despite the increasing use of Rituximab (RTX) in ANCA-Associated Vasculitis (AAV), it remains unclear what the optimal dosing is, especially for maintenance. A deeper understanding of post-RTX BC repopulation is needed to better tailor treatment.

Methods

This is a single center, 10-year retrospective study including newly diagnosed, ANCA-positive patients with GPA/MPA receiving RTX induction with no fixed-schedule maintenance. CD19+BC were monitored with flow cytometry. Data were censored after repeat RTX.
Repopulation was defined as CD19+BC>10 cells/μl.

Results

The cohort included 71 AAV patients, with a majority of females (62%), MPA syndrome (75%) and MPO-ANCA positivity (75%). Most had renal involvement (79%), with median eGFR 23 ml/min/1.73m2 (IQR 9-48).
During median follow-up of 55 months, 44 patients (62%) repopulated BCs. Median time to repopulation was 39 months (range 7-102).
Comparing patients with/without repopulation at 12/24/36/48 months, there was a trend for lower flare risk and higher infection risk with ongoing BC depletion, reaching statistical significance only at 48 months (log-rank test).
In exploratory univariate Cox regression, risk of BC repopulation was positively associated with eGFR and female gender, with a trend for negative association with older age, MPA presentation (vs. GPA), and steroid pulses. Among these variables, only eGFR (HR 1.22 per 10 ml/min/1.73m2, 95%CI 1.04-1.43, p=0.016) and gender (HR 2.73 for female, 95%CI 1.39-5.38, p=0.004) were independent predictors of time to BC repopulation in the multivariate model (Figure 1).

Conclusion

A subset of AAV patients develop sustained post-RTX BC depletion, which associates with long-term reduced flare risk and increased infection risk. Renal impairment and male gender are key predictors of delayed BC repopulation. These observations further highlight the need for tailored immunosuppression.

Fig. 1: Expected time to BC repopulation curves across different eGFR groups and gender, according to multivariate Cox model