Prediction of relapses in PR3-ANCA-associated vasculitis by assessing responses of ANCA titres to treatment

Rheumatology (Oxford). 2006 Jun;45(6):724-9. doi: 10.1093/rheumatology/kei272. Epub 2006 Jan 6.

Abstract

Objective: We performed a retrospective evaluation of whether c-ANCA titres (indirect immunofluorescence) and anti-proteinase 3 (PR3)-ANCA levels (ELISA) at diagnosis and following immunosuppressive treatment are predictive of relapse of ANCA-associated vasculitis.

Methods: Patients diagnosed with PR3-ANCA-associated vasculitis between 1991 and 2002, with at least 2 yr of follow-up, and treated with cyclophosphamide and corticosteroids only (1991-1996) or switched to azathioprine after induction of remission with cyclophosphamide and corticosteroids (1997-2002) were included. ANCA were assessed by immunofluorescence and direct PR3-specific ELISA at diagnosis and 3, 6, 12, 18 and 24 months after diagnosis. Actuarial relapse-free survival was analysed with the log rank test.

Results: We studied 87 patients positive for PR3-ANCA: 46 were on cyclophosphamide maintenance therapy and 41 switched to azathioprine. Overall actuarial relapse-free survival was 72% at 2 yr and 34% at 5 yr. Relapse-free survival did not differ between patients on cyclophosphamide maintenance and patients switched to azathioprine maintenance (P = 0.34). Patients who became and stayed negative for c-ANCA (immunofluorescence) or PR3-ANCA (ELISA) until 24 months after diagnosis had a lower risk of relapse (P = 0.01 and P = 0.02, respectively). Positive c-ANCA (immunofluorescence) titres at 3 [relative risk (RR) 2.0; 95% confidence interval (CI) 1.2-3.8], 12 (RR 1.9; 95% CI 1.1-3.3), 18 (RR 2.9; 95% CI 1.3-4.6) and 24 months (RR 2.6; 95% CI 1.2-5.0) were significantly associated with relapse within 5 yr after diagnosis. PR3-ANCA levels >10 U/ml at 18 (RR 2.7, 95% CI 1.1-4.3) and 24 months (RR 4.6; 95% CI 1.2-6.3) were predictive of relapse within 5 yr. In the azathioprine group, a positive c-ANCA titre at the time of switching to azathioprine (RR 2.2; 95% CI 1.0-5.4) was associated with relapse.

Conclusion: Positive c-ANCA (immunofluorescence) and PR3-ANCA (ELISA) titres during early follow-up identify patients at increased risk of relapse.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Antineutrophil Cytoplasmic / blood*
  • Biomarkers / blood
  • Enzyme-Linked Immunosorbent Assay
  • Epidemiologic Methods
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Myeloblastin
  • Recurrence
  • Serine Endopeptidases / immunology*
  • Vasculitis / drug therapy
  • Vasculitis / immunology*

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • Biomarkers
  • Immunosuppressive Agents
  • Serine Endopeptidases
  • Myeloblastin