title: Positive classic antineutrophil cytoplasmic antibody (C-ANCA) titer at switch to azathioprine therapy associated with relapse in proteinase 3-related vasculitis.
abstract: OBJECTIVE
  To analyze disease-free survival in patients with antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis (AAV) treated with cyclophosphamide only or switched to azathioprine after 3 months of full remission while taking cyclophosphamide.
  
  
  METHODS
  We analyzed disease-free survival in all consecutive patients diagnosed with AAV between 1990 and 2000 at our center. Patients were treated with cyclophosphamide only (1990-1996) or switched to azathioprine after 3 months of remission while taking cyclophosphamide (1997-2000). All patients received at least 12 months of followup.
  
  
  RESULTS
  Of the total 128 patients, 53 (41%) relapsed. Forty-four of the 128 patients (34%) had been switched to azathioprine therapy. Disease-free survival at 2 and 4 years was 76% and 65% in the cyclophosphamide group compared with 76% and 51% in the azathioprine group. In patients with proteinase 3 (PR3) classic ANCA (C-ANCA)-associated vasculitis who were switched to azathioprine (n = 33), a positive C-ANCA titer at the moment of treatment switch (n = 13) was significantly associated with relapse (RR 2.6, 95% confidence interval 1.1-8.0; P = 0.04). In patients with a negative ANCA titer at the time of switch to azathioprine, disease-free survival at 2 and 4 years was 80% and 62%, which was identical to that for patients treated with cyclophosphamide only. In patients who were ANCA-positive at the time of treatment switch, disease-free survival at 2 and 4 years was only 58% and 17%.
  
  
  CONCLUSIONS
  Switching cyclophosphamide to azathioprine after induction of remission in patients with PR3-ANCA-associated vasculitis who are still ANCA-positive at the time of treatment switch is associated with a high risk of relapse.
authors.affiliation: University Hospital Maastricht, Maastricht, The Netherlands. m.slot@immuno.unimaas.nl
authors.forename: Marjan C
authors.initials: MC
authors.lastname: Slot
authors.forename: Jan Willem Cohen
authors.initials: JW
authors.lastname: Tervaert
authors.forename: Maarten M
authors.initials: MM
authors.lastname: Boomsma
authors.forename: Coen A
authors.initials: CA
authors.lastname: Stegeman
mesh_terms: D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D001379:Azathioprine / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D012697:Serine Endopeptidases / Q000276:immunology*; D014657:Vasculitis / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D012697:Serine Endopeptidases; D053146:Myeloblastin; D001379:Azathioprine