title: Prediction of relapses in PR3-ANCA-associated vasculitis by assessing responses of ANCA titres to treatment.
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.
  
  
  CONCLUSIONS
  Positive c-ANCA (immunofluorescence) and PR3-ANCA (ELISA) titres during early follow-up identify patients at increased risk of relapse.
authors.affiliation: Division of Clinical Immunology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 GZ Groningen, The Netherlands. j.sanders@int.umcg.nl
authors.forename: J-S F
authors.initials: JS
authors.lastname: Sanders
authors.forename: M G
authors.initials: MG
authors.lastname: Huitma
authors.forename: C G M
authors.initials: CG
authors.lastname: Kallenberg
authors.forename: C A
authors.initials: CA
authors.lastname: Stegeman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D004812:Epidemiologic Methods; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin; D012008:Recurrence; D012697:Serine Endopeptidases / Q000276:immunology*; D014657:Vasculitis / Q000188:drug therapy / Q000276:immunology*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; D007166:Immunosuppressive Agents; D012697:Serine Endopeptidases; D053146:Myeloblastin