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

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McAdoo, Stephen P 
Medjeral-Thomas, Nicholas 
Gopaluni, Seerapani  ORCID logo  https://orcid.org/0000-0002-1584-6186
Tanna, Anisha 
Mansfield, Nicholas 

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

Adolescent, Adult, Aged, Aged, 80 and over, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Antineoplastic Combined Chemotherapy Protocols, Azathioprine, Case-Control Studies, Cohort Studies, Cyclophosphamide, Disease Progression, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Kidney Diseases, Kidney Failure, Chronic, Male, Middle Aged, Prognosis, Remission Induction, Rituximab, Survival Rate, Young Adult
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Nephrol Dial Transplant
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Oxford University Press (OUP)
Cambridge University Hospitals NHS Foundation Trust (CUH) (3819-1617-16)