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Long-term follow-up of a combined rituximab and cyclophosphamide regimen in renal anti-neutrophil cytoplasm antibody-associated vasculitis

McAdoo, SP; Medjeral-Thomas, N; Gopaluni, S; Tanna, A; Mansfield, N; Galliford, J; Griffith, M; ... Pusey, CD; + view all (2019) Long-term follow-up of a combined rituximab and cyclophosphamide regimen in renal anti-neutrophil cytoplasm antibody-associated vasculitis. Nephrology Dialysis Transplantation , 34 (1) pp. 63-73. 10.1093/ndt/gfx378. Green open access

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Abstract

Background: Current 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. / Methods: We 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. / Results: At 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. / Conclusions: This 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.

Type: Article
Title: Long-term follow-up of a combined rituximab and cyclophosphamide regimen in renal anti-neutrophil cytoplasm antibody-associated vasculitis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/ndt/gfx378
Publisher version: https://doi.org/10.1093/ndt/gfx378
Language: English
Additional information: Copyright © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: ANCA-associated vasculitis, cyclophosphamide, granulomatosis with polyangiitis, microscopic polyangiitis, rituximab
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10039713
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