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Clinical outcomes of treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis based on ANCA type
  1. Sebastian Unizony1,
  2. Miguel Villarreal2,
  3. Eli M Miloslavsky1,
  4. Na Lu1,
  5. Peter A Merkel3,
  6. Robert Spiera4,
  7. Philip Seo5,
  8. Carol A Langford6,
  9. Gary S Hoffman6,
  10. CG M Kallenberg7,
  11. E William St. Clair8,
  12. David Ikle2,
  13. Nadia K Tchao9,
  14. Linna Ding10,
  15. Paul Brunetta11,
  16. Hyon K Choi1,
  17. Paul A Monach12,
  18. Fernando Fervenza13,
  19. John H Stone1,
  20. Ulrich Specks13
  21. for the RAVE-ITN Research Group
  1. 1Massachusetts General Hospital, Boston, Massachusetts, USA
  2. 2Rho, Chapel Hill, North Carolina, USA
  3. 3University of Pennsylvania School of Medicine, Philadelphia, USA
  4. 4Hospital for Special Surgery, New York, New York, USA
  5. 5Johns Hopkins University, Baltimore, Maryland, USA
  6. 6Cleveland Clinic, Cleveland, Ohio, USA
  7. 7University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
  8. 8Duke University Medical Center, Durham, North Carolina, USA
  9. 9Immune Tolerance Network, San Francisco, California, USA
  10. 10National Institute of Allergy & Infectious Disease/Division of Allergy, Immunology, & Transplantation (NIAID/DAIT), Bethesda, Maryland, USA
  11. 11Genentech, South San Francisco, California, USA
  12. 12Boston University School of Medicine, Boston, Massachusetts, USA
  13. 13Mayo Clinic, Rochester, Minnesota, USA
  1. Correspondence to Dr John H Stone, Rheumatology Unit, Yawkey 2C, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; jhstone{at}mgh.harvard.edu

Abstract

Objective To evaluate whether the classification of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) according to ANCA type (anti-proteinase 3 (PR3) or anti-myeloperoxidase (MPO) antibodies) predicts treatment response.

Methods Treatment responses were assessed among patients enrolled in the Rituximab in ANCA-associated Vasculitis trial according to both AAV diagnosis (granulomatosis with polyangiitis (GPA)/microscopic polyangiitis (MPA)) and ANCA type (PR3-AAV/MPO-AAV). Complete remission (CR) was defined as disease activity score of 0 and successful completion of the prednisone taper.

Results PR3-AAV patients treated with rituximab (RTX) achieved CR at 6 months more frequently than did those randomised to cyclophosphamide (CYC)/azathioprine (AZA) (65% vs 48%; p=0.04). The OR for CR at 6 months among PR3-AAV patients treated with RTX as opposed to CYC/AZA was 2.11 (95% CI 1.04 to 4.30) in analyses adjusted for age, sex and new-onset versus relapsing disease at baseline. PR3-AAV patients with relapsing disease achieved CR more often following RTX treatment at 6 months (OR 3.57; 95% CI 1.43 to 8.93), 12 months (OR 4.32; 95% CI 1.53 to 12.15) and 18 months (OR 3.06; 95% CI 1.05 to 8.97). No association between treatment and CR was observed in the MPO-AAV patient subset or in groups divided according to AAV diagnosis.

Conclusions Patients with PR3-AAV respond better to RTX than to CYC/AZA. An ANCA type-based classification may guide immunosuppression in AAV.

Trial registration number NCT00104299; post-results.

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