Combined Rituximab-Cyclophosphamide for AAV

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A combined regimen of rituximab and cyclophosphamide improves long-term outcomes in patients with renal anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), reports a study in Nephrology Dialysis Transplantation.

The study included 66 patients with AAV and biopsy-confirmed renal involvement. All were treated with a regimen of oral corticosteroids and rituximab plus low-dose pulsed intravenous cyclophosphamide. Maintenance therapy consisted of azathioprine and tapered steroid.

Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS), along with monitoring of estimated glomerular filtration rate (eGFR). Median follow-up was 56 months. Outcomes were compared with those of 198 propensity-matched patients drawn from previous European Vasculitis Study Group trials.

At baseline, median BVAS score was 19 and eGFR 25 mL/min. By 6 months, patients had received median cumulative doses of 2 g of rituximab, 3 g of cyclophosphamide, and 4.2 g of corticosteroids. At that time, 94% had achieved disease remission, defined as a BVAS score of 0.

At 5 years, the patient survival rate was 84% and renal survival 95%. Eighty-four percent of patients became ANCA-negative. Fifty-seven percent of patients remained B cell-depleted (less than 10 cells/µL) through 2 years; this group had a 15% rate of major relapse at 5 years. Serious infections occurred at a rate of 1.24 per 10 patient-years. Compared to controls from previous trials, the combined rituximab-cyclophosphamide regimen was associated with lower rates of death, hazard ratio (HR) 0.29; progression to end-stage renal disease, HR 0.20; and relapse, HR 0.49.

Current guidelines for organ-threatening ANCA-associated AAV recommend the use of rituximab or cyclophosphamide. The authors call for controlled trials to evaluate the utility of combination drug regimens for treatment of AAV [McAdoo SP, et al. Long-term follow-up of a combined rituximab and cyclophosphamide regimen in renal anti-neutrophil cytoplasm antibody-associated vasculitis. Kidney Int 2019; 34:63–73].