332. Adding low dose cyclophosphamide to rituximab is associated with sustained remission in ANCA vasculitis patients

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 evaluated this premise by retrospectively analyzing our data derived from a pragmatic, clinical approach in patients with severe AAV.

Methods: Patients diagnosed with AAV who were treated with RTX for remission-induction in the Maastricht University Medical Centre between March 2007 and January 2019, were screened for eligibility. Remission-induction consisted of either RTX (2x 1000mg two times) or RTX-CYC (2x 1000mg RTX and 2x 15mg/kg CYC intravenously). Corticosteroid tapering was identical in both groups. RTX during the maintenance phase was tailored according to CD19+ B cell repopulation (≥5 cells/ µL) and/or a rise in ANCA level, combined with clinical parameters, without signs of a major relapse. The primary outcome variable was major relapse rate after 2 and 5 years. Secondary outcome variables were clinical data including infections, end stage renal disease, malignancy, and mortality and laboratory parameters including renal function, CRP, MPO- or PR3-ANCA and immunoglobulin levels, and B- and T-cell subsets .
 

Results:  Of the 246 patients with active AAV screened for the study, 28 patients received RTX only and 34 patients received RTX-CYC for remission-induction, both with a subsequent tailored RTX maintenance regimen. All patients were followed for at least 2 years with a median follow-up of 48 months (IQR 24-60). Patient characteristics at baseline are depicted in Figure 1. Biopsy proven renal involvement was more prevalent in the RTX-CYC patients (85.3%) compared to patients treated RTX only (60.7%) (P = 0.028). Baseline serum creatinine and delta serum creatinine after two years did not differ significantly with a median of -6.5 µmol/L (IQR -8.5-14.8) in the RTX only group and -0.5 µmol/L (IQR -30.3-29.5) in the RTX-CYC group (P = 0.737). Relapse rates within 2 years were significantly higher in the RTX only group (n=7 (28.0%) when compared to the RTX-CYC group(n=1 (3.2%); 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 were not significantly different. 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 in the first two years after remission-induction, predominantly with renal involvement. Future prospective studies are needed to examine the role of reconstituted B cells and ANCA levels to better define tailor-made treatment decisions. 

Disclosures: None