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

Clin J Am Soc Nephrol. 2014 Sep 5;9(9):1571-6. doi: 10.2215/CJN.00100114. Epub 2014 Jun 26.

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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / drug therapy*
  • Azathioprine / therapeutic use*
  • Cyclophosphamide / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Maintenance Chemotherapy*
  • Male
  • Middle Aged
  • Prospective Studies
  • Time Factors

Substances

  • Immunosuppressive Agents
  • Cyclophosphamide
  • Azathioprine