title: Long-term follow-up of cyclophosphamide compared with azathioprine for initial maintenance therapy in ANCA-associated vasculitis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors: Departments of Medicine and Clinical Epidemiology and Biostatistics, Population Health Research Institute, McMaster University and Population Health Research Institute, Hamilton, Ontario, Canada; lastwalsh1975@gmail.com.
authors: Michael
authors: M
authors: Walsh
authors: Departments of Infectious Diseases and Rheumatology and.
authors: Mikkel
authors: M
authors: Faurschou
authors: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands;
authors: Annelies
authors: A
authors: Berden
authors: Renal Unit, Royal Berkshire Hospital, Reading, United Kingdom;
authors: Oliver
authors: O
authors: Flossmann
authors: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands;
authors: Ingeborg
authors: I
authors: Bajema
authors: Competence Centre for Clinical Research, University Hospital Lund, Lund, Sweden;
authors: Peter
authors: P
authors: Hoglund
authors: Renal Unit, Addenbrooke's Hospital, Cambridge, United Kingdom;
authors: Rona
authors: R
authors: Smith
authors: Nephrology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark;
authors: Wladimir
authors: W
authors: Szpirt
authors: Department of Nephrology and Transplantation, Skane University Hospital, Malmö, Sweden; and.
authors: Kerstin
authors: K
authors: Westman
authors: Department of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.
authors: Charles D
authors: CD
authors: Pusey
authors: Renal Unit, Addenbrooke's Hospital, Cambridge, United Kingdom;
authors: David R W
authors: DR
authors: Jayne
mesh_terms: D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000188:drug therapy*; D001379:Azathioprine / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D001379:Azathioprine
keywords: GN; epidemiology; outcomes; randomized controlled trials; vasculitis