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Extended report
Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis
  1. Mark A Little1,
  2. Peter Nightingale2,
  3. C A Verburgh3,
  4. Thomas Hauser4,
  5. Kirsten De Groot5,
  6. Caroline Savage1,
  7. David Jayne6,
  8. Lorraine Harper1
  9. on behalf of the European Vasculitis Study (EUVAS) Group
  1. 1Renal Institute of Birmingham, School of Infection, Immunity and Inflammation, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, UK
  2. 2Wolfson Centre, Queen Elizabeth Hospital, Birmingham, UK
  3. 3Kennemer Gasthuis Boerhaavelaan, 22 Haarlem, 2035 RC, The Netherlands
  4. 4Immunologie-Zentrum Zürich, Zurich, Switzerland
  5. 5Medical Department, Klinikum Offenbach, Offenbach, Germany
  6. 6Nephrology and Transplantation, Addenbrooke's Hospital, Cambridge, UK
  1. Correspondence to Dr Lorraine Harper, Renal Institute of Birmingham, School of Infection, Immunity and Inflammation, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK; l.harper{at}


Objective To contrast the effect of the burden of vasculitis activity with the burden of adverse events on 1-year mortality of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).

Methods This study assessed the outcome and adverse events in patients prospectively recruited to four European AAV clinical trials. Data on 524 patients with newly diagnosed AAV were included. The burden of adverse events was quantified using a severity score for leucopenia, infection and other adverse events, with an additional weighting for follow-up duration. A ‘combined burden of events’ (CBOE) score was generated for each patient by summing the individual scores. Vasculitis severity was quantified using the Birmingham vasculitis activity score and glomerular filtration rate (GFR).

Results 1-year mortality probability was 11.1%; 59% and 14% of deaths were caused by therapy-associated adverse events and active vasculitis, respectively. Using Cox regression analysis, infection score (p<0.001), adverse event score (p<0.001), leucopenia score (p<0.001) and GFR (p=0.002) were independently associated with mortality. The risk of 1-year mortality remained low (5%) with CBOE scores less than 7, but increased dramatically with scores above this. Hazard ratio for death with a CBOE greater than 7 was 14.4 (95% CI 8.4 to 24.8). Age and GFR were independent predictors of CBOE score.

Conclusions The greatest threat to patients with AAV in the first year of therapy is from adverse events rather than active vasculitis. The accumulation of adverse events, monitored using this scoring method, should prompt increased awareness that the patient is at high risk of death.

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  • Funding Funding for this study was provided by the Higher Education Funding Council of England (HEFCE), the European Union (European Community Systemic Vasculitis Trial project, contract nos BMH1-CT93-1078 and CIPD-CT94-0307, and the Associated Vasculitis European Randomised Trial project, contract nos BMH4-CT97–2328 and IC20-CT97-0019), European Union League Against Rheumatism project grant 2004–7 EULAR Standardisation of Disease Assessment in Systemic Vasculitis, and the Renal Association, UK.

  • Ethics approval Each of the four trials had full ethics approval.

  • Provenance and peer review Not commissioned; externally peer reviewed.