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Randomized Controlled Trial
. 2014 Sep 5;9(9):1571-6.
doi: 10.2215/CJN.00100114. Epub 2014 Jun 26.

Long-term follow-up of cyclophosphamide compared with azathioprine for initial maintenance therapy in ANCA-associated vasculitis

Michael Walsh  1 , Mikkel Faurschou  2 , Annelies Berden  3 , Oliver Flossmann  4 , Ingeborg Bajema  3 , Peter Hoglund  5 , Rona Smith  6 , Wladimir Szpirt  7 , Kerstin Westman  8 , Charles D Pusey  9 , David R W Jayne  6 ; European Vasculitis Study Group
Collaborators, Affiliations
Randomized Controlled Trial

Long-term follow-up of cyclophosphamide compared with azathioprine for initial maintenance therapy in ANCA-associated vasculitis

Michael Walsh et al. Clin J Am Soc Nephrol. .

Abstract

Background and objectives: Treatment with azathioprine within 3 months of remission induction with cyclophosphamide is a common treatment strategy for patients with ANCA-associated vasculitis. This study comprised patients undergoing long-term follow-up who were randomly allocated to azathioprine after 3-6 months or after 12 months of cyclophosphamide treatment.

Design, setting, participants, & measurements: Patients from 39 European centers between 1995 and 1997 with a new diagnosis of ANCA-associated vasculitis that involved the kidneys or another vital organ were eligible. At the time of diagnosis, participants were randomly allocated to convert to azathioprine after 3-6 months (the azathioprine group) or after 12 months of cyclophosphamide (the cyclophosphamide group). Patients who did not achieve a remission within 6 months were excluded. This study assessed relapses, ESRD, and death during long-term follow-up.

Results: Patients were allocated to the azathioprine group (n=71) and the cyclophosphamide group (n=73). Of these patients, 63 (43.8%) developed a relapse, 35 (24.3%) developed a renal relapse, 13 (9.0%) developed ESRD, and 21 (14.6%) died. Although there were worse outcomes in the azathioprine group, none were statistically significant. The subdistribution hazard ratio [sHR] for relapse was 1.63 (95% confidence interval [95% CI], 0.99 to 2.71), the composite of relapse or death hazard ratio [HR] was 1.59 (95% CI, 1.00 to 2.54), the ESRD sHR was 1.71 (95% CI, 0.56 to 5.19), and the death HR was 0.75 (95% CI, 0.32 to 1.79).

Conclusions: It remains uncertain whether converting to azathioprine after 3-6 months of induction cyclophosphamide therapy is as effective as converting after 12 months. Outcomes are still poor for this group of patients and further research is required to determine the optimal timing of maintenance therapy.

Keywords: GN; epidemiology; outcomes; randomized controlled trials; vasculitis.

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Figures

Figure 1.
Figure 1.
Patient flow. AZA, azathioprine group; CYC, cyclophosphamide group.
Figure 2.
Figure 2.
Cumulative incidence of relapse of ANCA-associated vasculitis by allocated maintenance treatment group. Cumulative incidence is adjusted for the competing risk of death. AZA, azathioprine group; CYC, cyclophosphamide group.
See this image and copyright information in PMC

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