Kidney Week

Abstract: TH-PO508

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

Session Information

• Glomerular Diseases: Clinical, Outcomes, Trials - I
  November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

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

Federica Mescia,

• Salviani, Chiara, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy

Chiara Salviani,

• Affatato, Stefania, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy

Stefania Affatato,

• Tonoli, Mattia, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy

Mattia Tonoli,

• Guerini, Alice, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy

Alice Guerini,

• Tedesco, Martina, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy

Martina Tedesco,

• Moratto, Daniele, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy

Daniele Moratto,

• Gregorini, Gina Alessandra, Independent researcher, Brescia, Italy

Gina Alessandra Gregorini,

• Chiarini, Marco, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy

Marco Chiarini,

• Scolari, Francesco, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy

Francesco Scolari,

• Alberici, Federico, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy

Federico Alberici,

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