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Risk factors for treatment failures in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis

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Abstract

In the past several years, significant progress has occurred in the therapeutic management of antineutrophil cytoplasmic antibody-associated vasculitis. This has resulted in improved survival rates for all members of this group of inflammatory vascular disorders. However, the rate of treatment failure or resistance and relapse has remained relatively constant despite therapeutic advances. This article reviews risk factors associated with these failures, with hopes that better understanding may lead to improved therapeutic responses and less therapyrelated toxicity.

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References and Recommended Reading

  1. Phillip R, Luqmani R: Mortality in systemic vasculitis: a systematic review. Clin Exp Rheumatol 2008, 26(Suppl 51):S94–S104.

    CAS  PubMed  Google Scholar 

  2. Walton E: Giant-cell granuloma of the respiratory tract (Wegener’s granulomatosis). BMJ 1958, 2:265–270.

    Article  CAS  PubMed  Google Scholar 

  3. Fauci A, Wolff S: Wegener’s granulomatosis: studies in eighteen patients and a review of the literature. Medicine 1973, 52:53–61.

    Article  Google Scholar 

  4. Hoffman G, Kerr G, Leavitt R, et al.: Wegener’s granulomatosis: an analysis of 158 patients. Ann Intern Med 1992, 116:488–498.

    CAS  PubMed  Google Scholar 

  5. Guillevin L, Cordier J-F, Lhote F, et al.: A prospective, multicenter, randomized trial comparing steroids and pulse cyclophosphamide versus steroids and oral cyclophosphamide in the treatment of generalized Wegener’s granulomatosis. Arthritis Rheum 1997, 40:2187–2198.

    Article  CAS  PubMed  Google Scholar 

  6. de Groot K, Harper L, Jayne DR: Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med 2009, 150:670–680.

    PubMed  Google Scholar 

  7. Kallenberg CGM: Pathogenesis of PR3-ANCA associated vasculitis. J Autoimmun 2008, 30:29–36.

    Article  CAS  PubMed  Google Scholar 

  8. Fortin PM, Tejani AM, Bassett K, Musini VM: Intravenous immunoglobulin as adjuvant therapy for Wegener’s granulomatosis. Cochrane Database Syst Rev 2009, 8:CD007057.

    Google Scholar 

  9. Jones RB, Ferraro AJ, Jayne DR, et al.: A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2009, 60:2156–2168.

    Article  CAS  PubMed  Google Scholar 

  10. Pagnoux C, Nachman P, Chin H, et al.: Predictors of treatment resistance and relapse in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis: comparison of two independent cohorts. Arthritis Rheum 2008, 58:2908–2918.

    Article  PubMed  Google Scholar 

  11. Hauer HA, Bajema IM, van Houwelingen HC, et al.; European Vasculitis Study Group (EUVAS): Renal histology in ANCA-associated vasculitis: differences between diagnostic and serologic subgroups. Kidney Int 2002, 61:80–89.

    Article  PubMed  Google Scholar 

  12. Tamura N, Matsudaira R, Hirashima M, et al.: Two cases of refractory Wegener’s granulomatosis successfully treated with rituximab. Intern Med 2007, 46:409–414.

    Article  PubMed  Google Scholar 

  13. Reinhold-Keller E, Fink CO, Herlyn K, et al.: High rate of renal relapse in 71 patients with Wegener’s granulomatosis under maintenance of remission with low-dose methotrexate. Arthritis Rheum 2002, 47:326–332.

    Article  CAS  PubMed  Google Scholar 

  14. Birck R, Warnatz K, Lorenz HM, et al.: Deoxyspergualin in patients with refractory ANCA-associated systemic vasculitis: a six-month open-label trial to evaluate safety and efficacy. J Am Soc Nephrol 2003, 14:440–447.

    Article  CAS  PubMed  Google Scholar 

  15. Girard T, Mahr A, Noel AL, et al.: Are antineutrophil cytoplasmic antibodies a marker predictive of relapse in Wegener’s granulomatosis? A prospective study. Rheumatology (Oxford) 2001, 40:147–151.

    Article  CAS  Google Scholar 

  16. Hellmich B, Flossmann O, Gross WL, et al.: EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis. Ann Rheum Dis 2007, 66:605–617.

    Article  CAS  PubMed  Google Scholar 

  17. Koldingsnes W, Nossent H: Predictors of survival and organ damage in Wegener’s granulomatosis. Rheumatology (Oxford) 2002, 41:572–581.

    Article  CAS  Google Scholar 

  18. Neumann I, Kain R, Regele H, et al.: Histological and clinical predictors of early and late renal outcome in ANCA-associated vasculitis. Nephrol Dial Transplant 2005, 20:96–104.

    Article  PubMed  Google Scholar 

  19. Koldingsnes W, Nossent JC: Baseline features and initial treatment as predictors of remission and relapse in Wegener’s granulomatosis. J Rheumatol 2003, 30:80–88.

    PubMed  Google Scholar 

  20. Finkielman JD, Merkel PA, Schroeder D, et al.: Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis, Ann Intern Med 2007; 147:611–619.

    PubMed  Google Scholar 

  21. Wegener’s Granulomatosis Etanercept Trial (WGET) Research Group: Etanercept plus standard therapy for Wegener’s granulomatosis. N Engl J Med 2005, 352:351–361.

    Article  Google Scholar 

  22. De Groot K, Rasmussen N, Bacon PA, et al.: Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2005, 52:2461–2469.

    Article  PubMed  Google Scholar 

  23. Jayne D, Rasmussen N, Andrassy K, et al.: A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 2003, 349:36–44.

    Article  CAS  PubMed  Google Scholar 

  24. Smith KG, Jones RB, Burns SM, Jayne DR: Long-term comparison of rituximab treatment for refractory systemic lupus erythematosus and vasculitis: remission, relapse, and re-treatment. Arthritis Rheum 2006, 54:2970–2982.

    Article  CAS  PubMed  Google Scholar 

  25. Stasi R, Stipa E, Del Poeta G, et al.: Long-term observations of patients with anti-neutrophil cytoplasmic antibodyassociated vasculitis treated with rituximab. Rheumatology (Oxford) 2006, 45:1432–1436.

    Article  CAS  Google Scholar 

  26. Keogh KA Wylam ME, Stone JH, Specks U: Induction of remission by B lymphocyte depletion in eleven patients with refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2005, 52:262–268.

    Article  PubMed  Google Scholar 

  27. Ferraro AJ, Day CJ, Drayson MT, Savage CO: Effective therapeutic use of rituximab in refractory Wegener’s granulomatosis. Nephrol Dial Transplant 2005, 20:622–625.

    Article  PubMed  Google Scholar 

  28. Tamura N, Matsudaira R, Hirashima M, et al.: Two cases of refractory Wegener’s granulomatosis successfully treated with rituximab. Intern Med 2007, 46:409–414.

    Article  PubMed  Google Scholar 

  29. Albert D, Dunham J, Khan S, et al.: Variability in the biological response to anti-CD20 B cell depletion in systemic lupus erythematosus. Ann Rheum Dis 2008, 67:1724–1731.

    Article  CAS  PubMed  Google Scholar 

  30. Sanders JS, Stassen PM, van Rossum AP, et al.: Risk factors for relapse in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis: tools for treatment decisions? Clin Exp Rheumatol 2004, 22(6 Suppl 36):S94–S101.

    CAS  PubMed  Google Scholar 

  31. Nachman PH, Hogan SL, Jennette JC, Falk RJ: Treatment response and relapse in antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. J Am Soc Nephrol 1996, 7:33-39.

    Google Scholar 

  32. Reynolds WF, Stegeman CA, Cohen Tervaert JW: -463 G/A myeloperoxidase promoter polymorphism is associated with clinical manifestation and the course of disease in MPO-ANCA-associated vasculitis. Clin Immunol 2002, 103:154–160.

    Article  CAS  PubMed  Google Scholar 

  33. Stegeman CA: Anti-neutrophil cytoplasmic antibody (ANCA) levels directed against proteinase-3 and myeloperoxidase are helpful in predicting disease relapse in ANCA-associated small-vessel vasculitis. Nephrol Dial Transplant 2002, 17:2077–2080.

    Article  CAS  PubMed  Google Scholar 

  34. Hogan SL, Falk RJ, Chin H, et al.: Predictors of relapse and treatment resistance in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis. Ann Intern Med 2005, 143:621–631.

    PubMed  Google Scholar 

  35. Mukhtyar C, Luqmani R: Disease-specific quality indicators, guidelines, and outcome measures in vasculitis. Clin Exp Rheumatol 2007, 25(6 Suppl 47):120–129.

    CAS  PubMed  Google Scholar 

  36. Sanders JS, Huitma MG, Kallenberg CG, Stegeman CA: Prediction of relapses in PR3-ANCA-associated vasculitis by assessing responses of ANCA titres to treatment. Rheumatology (Oxford) 2006, 45:724–729.

    Article  CAS  Google Scholar 

  37. Pettersson E, Heigl Z: Antineutrophil cytoplasmic antibody (cANCA and pANCA) titers in relation to disease activity in patients with necrotizing vasculitis: a longitudinal study. Clin Nephrol 1992, 37:219–228.

    CAS  PubMed  Google Scholar 

  38. Slot MC, Cohen Tervaert JW, Boomsma MM, Stegeman CA: Positive classic antineutrophil cytoplasmic antibody (C-ANCA) titer at switch to azathioprine therapy associated with relapse in proteinase 3-related vasculitis. Arthritis Rheum 2004, 51:269–273.

    Article  CAS  PubMed  Google Scholar 

  39. Nakabayashi K, Arimura Y, Yoshihara K, et al.: Classification of clinical subtypes, patient survival, kidney prognosis, and relapse in patients with MPO-ANCA-associated vasculitis: a single-center experience. Mod Rheumatol 2009, 19:420–426.

    Article  PubMed  Google Scholar 

  40. Zycinska K, Wardyn KA, Zielonka TM, et al.: Chronic crusting, nasal carriage of Staphylococcus aureus and relapse rate in pulmonary Wegener’s granulomatosis. J Physiol Pharmacol 2008, 59(Suppl 6):825–831.

    PubMed  Google Scholar 

  41. Christensson M, Pettersson E, Sundqvist KG, Christensson B: T cell activation in patients with ANCA-associated vasculitis: inefficient immune suppression by therapy. Clin Nephrol 2000, 54:435–442.

    CAS  PubMed  Google Scholar 

  42. Ohlson S, Wieslander J, Segelmark M: Low IL-10 levels during remission is associated with a risk of subsequent relapse. Kidney Blood Press Res 2003, 26:277.

    Google Scholar 

  43. Hruskova Z, Rihova Z, Mareckova H, et al.: Intracellular cytokine production in ANCA-associated vasculitis: low levels of interleukin-10 in remission are associated with a higher relapse rate in the long-term follow-up. Arch Med Res 2009, 40:276–284.

    Article  CAS  PubMed  Google Scholar 

  44. Dijstelbloem HM, Scheepers RH, Oost WW, et al.: FC gamma receptor polymorphisms in Wegener’s granulomatosis: risk factors for disease relapse. Arthritis Rheum 1999, 42:1823–1827.

    Article  CAS  PubMed  Google Scholar 

  45. Taylor SR, Salama AD, Joshi L, et al.: Rituximab is effective in the treatment of refractory ophthalmic Wegener’s granulomatosis. Arthritis Rheum 2009, 60:1540–1547.

    Article  PubMed  Google Scholar 

  46. Roccatello D, Baldovino S, Alpa M, et al.: Effects of anti-CD20 monoclonal antibody as a rescue treatment for ANCA-associated idiopathic systemic vasculitis with or without overt renal involvement. Clin Exp Rheumatol 2008, 26(3 Suppl 49):S67–S71.

    CAS  PubMed  Google Scholar 

  47. Stenová E, Mišttec S, Povinec P: FDG-PET/CT in large-vessel vasculitis: its diagnostic and follow-up role. Rheumatol Int 2009 Jul 9 (Epub ahead of print).

  48. Ohlsson S, Bakoush O, Tencer J, et al.: Monocyte chemoattractant protein 1 is a prognostic marker in ANCA-associated small vessel vasculitis. Mediators Inflamm 2009 Jul 5 (Epub ahead of print).

  49. Woywodt A, Goldberg C, Kirsch T, et al.: Circulating endothelial cells in relapse and limited granulomatous disease due to ANCA associated vasculitis. Ann Rheum Dis 2006, 65:164–168.

    Article  CAS  PubMed  Google Scholar 

  50. Hiemstra TF, Jayne D: Newer therapies for vasculitis. Best Pract Res Clin Rheumatol 2009, 23:379–389.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, Section of Rheumatology, Louisiana State University Health Sciences Center at New Orleans, 1542 Tulane Avenue, New Orleans, LA, 70112, USA

    Luis R. Espinoza

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  1. Vijay R. Karia
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  2. Luis R. Espinoza
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Correspondence to Luis R. Espinoza.

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Karia, V.R., Espinoza, L.R. Risk factors for treatment failures in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis. Curr Rheumatol Rep 11, 416–421 (2009). https://doi.org/10.1007/s11926-009-0061-x

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