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Kidney Week

Abstract: PO1625

Adding Low-Dose CYC to RTX Combined with a Tailored RTX Maintenance Regimen Seems to Favor Stable Remission in Severe ANCA Vasculitis

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Ysermans, Renee, Maastricht University Medical Center, Department of Internal Medicine, Maastricht, Netherlands
  • Busch, Matthias H., Maastricht University Medical Center, Department of Internal Medicine, Maastricht, Netherlands
  • Aendekerk, Joop, Maastricht University Medical Center, Department of Internal Medicine, Maastricht, Netherlands
  • van Paassen, Pieter, Maastricht University Medical Center, Department of Internal Medicine, Maastricht, Netherlands
Background

Rituximab (RTX) and cyclophosphamide (CYC) are effective remission-induction therapies in ANCA-associated vasculitis (AAV). High dose CYC is however considered toxic, whereas RTX monotherapy may increase the risk of relapse, depending on the choice of maintenance therapy and baseline disease severity. Particularly with renal involvement, stable remission will favor prognosis. In this respect, adding low dose CYC to RTX could be superior to RTX alone. We checked this premise by retrospectively analyzing our data derived from a pragmatic, clinical approach in patients with severe AAV.

Methods

Between 2007 and January 2019, 246 patients with severe active AAV, needing remission-induction therapy, were screened and 62 patients were included. Remission-induction consisted of either RTX (1000mg two times) or RTX-CYC (1000mg RTX and 15mg/kg CYC intravenously, two times). Corticosteroid tapering was identical in both groups. RTX during the maintenance phase was tailored according to either CD19+ B cell repopulation (≥5 cells/ µl) and/or a rise in ANCA level, combined with clinical symptoms, without signs of a major relapse. Primary outcome variables were major relapse rate and adverse events at 2 and 5 years, compared with the log-rank test.

Results

28 patients received RTX only and 34 patients received RTX-CYC. Disease presentation, severity of disease (BVAS), and laboratory parameters (serum creatinine, CRP, and total IgG) at baseline were similar. Renal involvement was more prevalent in the RTX-CYC patients (85.3%) as compared to RTX only (60.7%) (P = 0.028). Relapse rates within 2 years were significantly higher in the RTX only group (n=7 in RTX only, n=1 in RTX-CYC, P = 0.015), whereas the number of patients receiving RTX maintenance and the number of infusions did not differ. After 5 years, however, relapse rates did not differ (n=9 in RTX only, n=7 in RTX-CYC). The rate of infections, hypogammaglobulinemia, end stage renal disease, malignancies, and mortality did not differ after 2 and 5 years.

Conclusion

Adding low dose CYC to RTX is safe and may favor the prevention of major relapses in patients with severe AAV, predominantly with renal involvement. Future prospective studies are needed to examine the role of reconstituted B cells and ANCA features to better define tailor-made treatment decisions.