Long-term follow-up of a combined rituximab and cyclophosphamide regimen in renal anti-neutrophil cytoplasm antibody-associated vasculitis.
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Authors
McAdoo, Stephen P
Medjeral-Thomas, Nicholas
Tanna, Anisha
Mansfield, Nicholas
Galliford, Jack
Griffith, Megan
Levy, Jeremy
Cairns, Thomas D
Salama, Alan D
Pusey, Charles D
Publication Date
2019-01-31Journal Title
Nephrol Dial Transplant
ISSN
0931-0509
Publisher
Oxford University Press (OUP)
Volume
34
Issue
1
Pages
63-73
Language
eng
Type
Article
Metadata
Show full item recordCitation
McAdoo, S. P., Medjeral-Thomas, N., Gopaluni, S., Tanna, A., Mansfield, N., Galliford, J., Griffith, M., et al. (2019). Long-term follow-up of a combined rituximab and cyclophosphamide regimen in renal anti-neutrophil cytoplasm antibody-associated vasculitis.. Nephrol Dial Transplant, 34 (1), 63-73. https://doi.org/10.1093/ndt/gfx378
Abstract
Background. 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), 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 ¼ 0.004}, progression to end-stage renal disease (ESRD) [HR
0.20 (95% CI 0.06–0.65), P ¼ 0.007] and relapse [HR 0.49 (95%
CI 0.25–0.97), P ¼ 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 ut
Sponsorship
Cambridge University Hospitals NHS Foundation Trust (CUH) (3819-1617-16)
Identifiers
External DOI: https://doi.org/10.1093/ndt/gfx378
This record's URL: https://www.repository.cam.ac.uk/handle/1810/279890
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
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