Positive classic antineutrophil cytoplasmic antibody (C-ANCA) titer at switch to azathioprine therapy associated with relapse in proteinase 3-related vasculitis

Arthritis Rheum. 2004 Apr 15;51(2):269-73. doi: 10.1002/art.20234.


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%.

Conclusion: 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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antibodies, Antineutrophil Cytoplasmic / blood*
  • Azathioprine / administration & dosage*
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Male
  • Middle Aged
  • Myeloblastin
  • Prospective Studies
  • Recurrence
  • Remission Induction
  • Serine Endopeptidases / immunology*
  • Vasculitis / drug therapy*
  • Vasculitis / immunology*
  • Vasculitis / mortality


  • Antibodies, Antineutrophil Cytoplasmic
  • Immunosuppressive Agents
  • Cyclophosphamide
  • Serine Endopeptidases
  • Myeloblastin
  • Azathioprine