Abstract
ABSTRACTBackgroundCurrent guidelines advise that rituximab or cyclophosphamide should be used for the treatment of organ-threatening disease in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), although few studies have examined the efficacy and safety of these agents in combination.MethodsWe conducted a single-centre cohort study of 66 patients treated with a combination of oral corticosteroids, rituximab and low-dose pulsed intravenous cyclophosphamide followed by a maintenance regimen of azathioprine and tapered steroid for the treatment of biopsy-proven renal involvement in AAV. Patients were followed for a median of 56 months. Case–control analysis with 198 propensity-matched cases from European Vasculitis Study Group (EUVAS) trials compared long-term differences in relapse-free, renal and patient survival.ResultsAt entry, the median Birmingham Vasculitis Activity Score (BVAS) was 19 and estimated glomerular filtration rate was 25 mL/min. Cumulative doses of rituximab, cyclophosphamide and corticosteroids were 2, 3 and 4.2 g, respectively, at 6 months. A total of 94% of patients achieved disease remission by 6 months (BVAS < 0) and patient and renal survival were 84 and 95%, respectively, at 5 years. A total of 84% achieved ANCA-negative status and 57% remained B cell deplete at 2 years, which was associated with low rates of major relapse (15% at 5 years). The serious infection rate during long-term follow-up was 1.24 per 10 patient-years. Treatment with this regimen was associated with a reduced risk of death {hazard ratio [HR] 0.29 [95% confidence interval (CI) 0.125–0.675], P = 0.004}, progression to end-stage renal disease (ESRD) [HR 0.20 (95% CI 0.06–0.65), P = 0.007] and relapse [HR 0.49 (95% CI 0.25–0.97), P = 0.04] compared with propensity-matched patients enrolled in EUVAS trials.ConclusionsThis regimen is potentially superior to current standards of care, and controlled studies are warranted to establish the utility of combination drug approaches in the treatment of AAV.
Highlights
The past decade has seen B-cell depletion therapy using rituximab become an established treatment strategy in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), both for remission induction and remission maintenance
We report our extended experience using this regimen in a larger cohort with long-term follow-up and compare outcomes with patients treated with cyclophosphamide-based regimens in European Vasculitis Study Group (EUVAS) trials
Inclusion criteria were active AAV with renal involvement, as defined by the presence of circulating ANCA detected by indirect immunofluorescence (IIF) or antigenspecific assay and either (i) biopsy-proven pauci-immune glomerulonephritis or (ii) active urinary sediment and abnormal renal function in patients with evidence of glomerulonephritis on former biopsy
Summary
The past decade has seen B-cell depletion therapy using rituximab become an established treatment strategy in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), both for remission induction and remission maintenance. In 2010, two landmark randomized controlled trials, the Rituximab for ANCA-associated Vasculitis (RAVE) and Randomised Trial of Rituximab versus Cyclophosphamide for ANCA-associated Renal Vasculitis (RITUXVAS) studies [4, 5], suggested that it was non-inferior to treatment with cyclophosphamide for induction treatment in AAV. It was subsequently approved for this indication in 2011. Current guidelines advise that rituximab or cyclophosphamide should be used for the treatment of organthreatening disease in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), few studies have examined the efficacy and safety of these agents in combination. Treatment with this regimen was associated with a reduced risk of death {hazard ratio [HR] 0.29 [95% confidence interval (CI) 0.125–0.675],
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