Rheumatology Advance Access originally published online on January 6, 2006
Rheumatology 2006 45(6):724-729; doi:10.1093/rheumatology/kei272
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Prediction of relapses in PR3-ANCA-associated vasculitis by assessing responses of ANCA titres to treatment
Divisions of Clinical Immunology and 1 Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, The Netherlands.
Correspondence to: J.-S. Sanders, Department of Clinical Immunology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 GZ Groningen, The Netherlands. E-mail: j.sanders{at}int.umcg.nl
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.
KEY WORDS: ANCA-associated vasculitis, Relapse, Treatment switch, Follow-up, PR3-ANCA
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