1083: Treatment of ANCA-associated Vasculitis with Extreme Impairment of Renal Function: A Case-Control Study Comparing an Intensive B Cell Depletion Regimen with the Standard of Care Using Oral Cyclophosphamide
UNIVERSITA' DEGLI STUDI DI TORINO TURIN, Milan, Italy
Dario Roccatello1, Savino Sciascia2, Stefano Murgia1, Giacomo Quattrocchio1, Michela Ferro1, Emanuele De Simone1, Carla Naretto1, Antonella Barreca1, Daniela Rossi1, Vittorio Modena1 and Roberta Fenoglio1, 1University of Turin, Turin, Italy, 2University of Turin, Torino, Italy
Background/Purpose: Rituximab (RTX), an anti-CD20 monoclonal antibody, has shown to be an effective induction treatment for small-vessel vasculitis associated with antineutrophil cytoplasm antibodies (AAV) in both newly diagnosed and relapsing patients. However, the role of RTX in the management of the most severe cases of AAV remains to be fully elucidated.
The aim of the work was to assess both safety and efficacy of an intensified B-cell depletion therapy (IBCDT) protocol, including RTX, cyclophosphamide (CYC), and methylprednisolone pulses without additional maintenance immunosuppressive therapy compared to conventional therapy regimen based on oral CYC and steroids and prolonged maintenance therapy with azathioprine (AZA) in patients with AAV and severe renal injury.
Methods: A cohort of 15 AAV patients with the most severe features of AVV renal involvement (as < 15 ml/min GFR and histological findings of paucimmune necrotizing glomerulonephritis with more than 50% crescents of non-sclerotic glomeruli at the renal biopsy) was treated IBCDT and compared to compared to a control group of 10 patients with AAV treated with a conventional therapy regimen based on oral CYC and steroids and prolonged maintenance therapy with azathioprine (AZA).
Results: Complete clinical remission (BVAS 0) was observed at 6 months in 14 of 15 patients (93%). All cases treated with IBCDT who achieved a complete clinical remission experienced a depletion of peripheral blood B cells at the end of therapy. Of the 10 dialysis dependent patients at onset, 6 subjects (60%) experienced a functional recovery allowing the suspension of dialysis treatment. When compared to the control group, no statistically significant difference was observed in patients treated with IBCDT in terms of overall survival, 6-month therapeutic response rate, and 6-, and 12-month functional renal recovery. The cumulative total dose of CYC in the case group was on average 1 g/patient while in the control group on average 8.5 g / patient (p = 0.00008).
Conclusion: The results of this study showed that IBCDT appeared to be safe and has the same efficacy profile when compared to conventional therapy with CYC plus AZA in the management of the most severe patients with AAV. Additionally, this avoids the need of prolonged maintenance therapy for long, and limits the exposure to CYC with consequent reduced toxicity and drug-related side effect rates.
Disclosures: D. Roccatello, None; S. Sciascia, None; S. Murgia, None; G. Quattrocchio, None; M. Ferro, None; E. De Simone, None; C. Naretto, None; A. Barreca, None; D. Rossi, None; V. Modena, None; R. Fenoglio, None.
