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Abstract: FR-PO646

Maintenance of ANCA Vasculitis Remission by Intermittent Rituximab Dosing Based on B Cell Reconstitution vs. Serologic ANCA Flare

Session Information

Category: Glomerular Diseases

  • 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials

Authors

  • Zonozi, Reza, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Cortazar, Frank B., Vasculitis and Glomerular Disease Center, Albany, New York, United States
  • Nithagon, Pravarut, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Huizenga, Noah, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Jeyabalan, Anushya, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Niles, John, Massachusetts General Hospital, Boston, Massachusetts, United States
Background

Fixed-schedule rituximab dosing over 2 years is effective at maintaining remission for patients with ANCA vasculitis. However, rituximab is associated with adverse events. The ideal dosing strategy for long-term maintenance of remission remains unknown.

Methods

This is an open-label, single center, randomized and two-arm controlled trial. Inclusion criteria were AAV, in remission on fixed-rituximab for at least 2 years, and off other immunosuppression including steroids. Exclusion criteria were IgG level < 300 mg/dL and another disease with life expectancy < 36 months. BVAS, B cells and ANCA titers are monitored every 3 months. In the B cell arm, rituximab 1000 mg is reinfused once peripheral B cells are > 10 B cells/mm3. In the ANCA arm, rituximab 1000 mg is reinfused x 2 for significant ANCA titer increase. Randomization was stratified by ANCA serotype. The primary outcome measured was clinical relapse, defined by BVAS-WG ≥ 2. Secondary outcomes of interest included SAEs.

Results

57 subjects were randomized to the ANCA arm, and 58 patients to the B cell arm. The median follow-up time was 4.1 years (IQR, 2.5 - 5.0). At 3 years 4.1% (95% CI, 1.0 - 15.6) of patients in the B cell arm experienced a clinical relapse, compared to 20.5% (95% CI, 11.9 - 34.1) of patients in the ANCA arm (log-rank p = 0.045). 22 SAEs occurred in the ANCA arm, compared to 21 in the B cell arm (NS). Discontinuation rate of rituximab due to any SAE/AE(s) was 13.6% (95% CI, 6.7 – 26.4%) in the B cell arm, and 0% in the ANCA arm, at 3 years after entry (log-rank p = 0.02).

Conclusion

In patients with AAV in remission after 2 years of continuous rituximab, tailoring rituximab to B cell return is associated with lower rates of clinical relapse, but higher rates of drug discontinuation due to an adverse event, compared to tailoring rituximab to ANCA rise.

Figure 1. Kaplan-Meir curve to time to clinical relapse.