Treatment of ANCA-Associated Vasculitides

  • Loïc GuillevinEmail author
  • Loïc Raffray
  • Yann Nguyen
  • Benjamin Chaigne
  • Benjamin Terrier
Part of the Rare Diseases of the Immune System book series (RDIS)


A subgroup of systemic necrotizing vasculitides, antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAVs), are known to have circulating ANCA in >30–90% of the affected patients. Granulomatosis with polyangiitis (GPA, formerly Wegener’s granulomatosis), eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg–Strauss syndrome), and microscopic polyangiitis (MPA) are AAVs [1]. Renal-limited vasculitis, another AAV, is a bit of a question mark, as it is a disease that initially affects the kidney but could then evolve to become MPA or GPA. All AAVs affect small-sized vessels, and ANCA are thought to play a role in their pathogeneses. Due to our improved understanding of AAV pathophysiological mechanisms and identification of their cellular and molecular targets, AAV treatments are now more specific than they had been in the past.


Vasculitis ANCA Corticosteroids Immunosuppressants Plasma exchange Rituximab Mepolizumab 


  1. 1.
    Jennette JC, Falk RJ, Bacon PA, et al. 2012 Revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Arthritis Rheum. 2013;65(1):1–11.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Guillevin L, Pagnoux C, Seror R, et al. The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Medicine (Baltimore). 2011;90(1):19–27.CrossRefGoogle Scholar
  3. 3.
    Serra A, Cameron JS, Turner DR, et al. Vasculitis affecting the kidney: presentation, histopathology and long-term outcome. Q J Med. 1984;53(210):181–207.Google Scholar
  4. 4.
    Savage CO, Winearls CG, Evans DJ, Rees AJ, Lockwood CM. Microscopic polyarteritis: presentation, pathology and prognosis. Q J Med. 1985;56(220):467–83.Google Scholar
  5. 5.
    D’Agati V, Chander P, Nash M, Mancilla-Jimenez R. Idiopathic microscopic polyarteritis nodosa: ultrastructural observations on the renal vascular and glomerular lesions. Am J Kidney Dis. 1986;7(1):95–110.CrossRefGoogle Scholar
  6. 6.
    Adu D, Howie AJ, Scott DG, Bacon PA, McGonigle RJ, Micheal J. Polyarteritis and the kidney. Q J Med. 1987;62(239):221–37.Google Scholar
  7. 7.
    Guillevin L, Durand-Gasselin B, Cevallos R, et al. Microscopic polyangiitis: clinical and laboratory findings in eighty-five patients. Arthritis Rheum. 1999;42(3):421–30.CrossRefGoogle Scholar
  8. 8.
    Ribi C, Cohen P, Pagnoux C, et al. Treatment of polyarteritis nodosa and microscopic polyangiitis without poor-prognosis factors: a prospective randomized study of one hundred twenty-four patients. Arthritis Rheum. 2010;62(4):1186–97.CrossRefGoogle Scholar
  9. 9.
    Puéchal X, Pagnoux C, Baron G, et al. Adding azathioprine to remission-induction glucocorticoids for eosinophilic granulomatosis with polyangiitis (Churg–Strauss), microscopic polyangiitis, or polyarteritis nodosa without poor prognosis factors: a randomized, controlled trial. Arthritis Rheumatol. 2017;69(11):2175–86.CrossRefGoogle Scholar
  10. 10.
    Samson M, Puéchal X, Devilliers H, et al. Long-term follow-up of a randomized trial on 118 patients with polyarteritis nodosa or microscopic polyangiitis without poor-prognosis factors. Autoimmun Rev. 2014;13(2):197–205.CrossRefGoogle Scholar
  11. 11.
    Groh M, Pagnoux C, Baldini C, et al. Eosinophilic granulomatosis with polyangiitis (Churg–Strauss) (EGPA) Consensus Task Force recommendations for evaluation and management. Eur J Intern Med. 2015;26(7):545–53.CrossRefGoogle Scholar
  12. 12.
    Yates M, Watts RA, Bajema IM, et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis. 2016;75(9):1583–94.CrossRefGoogle Scholar
  13. 13.
    Guillevin L, Guittard T, Bletry O, Godeau P, Rosenthal P. Systemic necrotizing angiitis with asthma: causes and precipitating factors in 43 cases. Lung. 1987;165(1):165–72.CrossRefGoogle Scholar
  14. 14.
    Kostianovsky A, Charles P, Alves J-F, et al. Immunogenicity and safety of seasonal and 2009 pandemic A/H1N1 influenza vaccines for patients with autoimmune diseases: a prospective, monocentre trial on 199 patients. Clin Exp Rheumatol. 2012;30(Suppl 70):S83–9.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Adler S, Krivine A, Weix J, et al. Protective effect of A/H1N1 vaccination in immune-mediated disease—a prospectively controlled vaccination study. Rheumatology (Oxford). 2012;51(4):695–700.CrossRefGoogle Scholar
  16. 16.
    Westra J, van Assen S, Wilting KR, et al. Rituximab impairs immunoglobulin (Ig)M and IgG (subclass) responses after influenza vaccination in rheumatoid arthritis patients. Clin Exp Immunol. 2014;178(1):40–7.CrossRefGoogle Scholar
  17. 17.
    Moulis G, Lapeyre-Mestre M, Mahévas M, Montastruc J-L, Sailler L. Need for an improved vaccination rate in primary immune thrombocytopenia patients exposed to rituximab or splenectomy. A nationwide population-based study in France. Am J Hematol. 2015;90(4):301–5.CrossRefGoogle Scholar
  18. 18.
    Pagnoux C, Quéméneur T, Ninet J, et al. Treatment of systemic necrotizing vasculitides in patients aged sixty-five years or older: results of a multicenter, open-label, randomized controlled trial of corticosteroid and cyclophosphamide–based induction therapy. Arthritis Rheumatol. 2015;67(4):1117–27.CrossRefGoogle Scholar
  19. 19.
    Fauci AS, Katz P, Haynes BF, Wolff SM. Cyclophosphamide therapy of severe systemic necrotizing vasculitis. N Engl J Med. 1979;301(5):235–8.CrossRefGoogle Scholar
  20. 20.
    Guillevin L, Cordier JF, 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(12):2187–98.CrossRefGoogle Scholar
  21. 21.
    de Groot K, Harper L, Jayne DRW, et al. Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med. 2009;150(10):670–80.CrossRefGoogle Scholar
  22. 22.
    Harper L, Morgan MD, Walsh M, et al. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up. Ann Rheum Dis. 2012;71(6):955–60.CrossRefGoogle Scholar
  23. 23.
    Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221–32.CrossRefGoogle Scholar
  24. 24.
    Jones RB, Cohen Tervaert JW, Hauser T, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010;363(3):211–20.CrossRefGoogle Scholar
  25. 25.
    Heijl C, Harper L, Flossmann O, et al. Incidence of malignancy in patients treated for antineutrophil cytoplasm antibody-associated vasculitis: follow-up data from European Vasculitis Study Group clinical trials. Ann Rheum Dis. 2011;70(8):1415–21.CrossRefGoogle Scholar
  26. 26.
    Le Guenno G, Mahr A, Pagnoux C, Dhote R, Guillevin L, for the French Vasculitis Study Group. Incidence and predictors of urotoxic adverse events in cyclophosphamide-treated patients with systemic necrotizing vasculitides. Arthritis Rheum. 2011;63(5):1435–45.CrossRefGoogle Scholar
  27. 27.
    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(8):2461–9.CrossRefGoogle Scholar
  28. 28.
    Jones RB, Hiemstra TF, Ballarin J, et al. Mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA-associated vasculitis: a randomised, non-inferiority trial. Ann Rheum Dis. 2019;78(3):399–405.CrossRefGoogle Scholar
  29. 29.
    Jayne DR, Davies MJ, Fox CJ, Black CM, Lockwood CM. Treatment of systemic vasculitis with pooled intravenous immunoglobulin. Lancet. 1991;337(8750):1137–9.CrossRefGoogle Scholar
  30. 30.
    Richter C, Schnabel A, Csernok E, de Groot K, Reinhold-Keller E, Gross WL. Treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis with high-dose intravenous immunoglobulin. Clin Exp Immunol. 1995;101(1):2–7.CrossRefGoogle Scholar
  31. 31.
    Jayne DR, Lockwood CM. Intravenous immunoglobulin as sole therapy for systemic vasculitis. Br J Rheumatol. 1996;35(11):1150–3.CrossRefGoogle Scholar
  32. 32.
    Jayne DR, Chapel H, Adu D, et al. Intravenous immunoglobulin for ANCA-associated systemic vasculitis with persistent disease activity. QJM. 2000;93(7):433–9.CrossRefGoogle Scholar
  33. 33.
    Pusey CD, Rees AJ, Evans DJ, Peters DK, Lockwood CM. Plasma exchange in focal necrotizing glomerulonephritis without anti-GBM antibodies. Kidney Int. 1991;40(4):757–63.CrossRefGoogle Scholar
  34. 34.
    Glöckner WM, Sieberth HG, Wichmann HE, et al. Plasma exchange and immunosuppression in rapidly progressive glomerulonephritis: a controlled, multi-center study. Clin Nephrol. 1988;29(1):1–8.PubMedGoogle Scholar
  35. 35.
    Guillevin L, Cevallos R, Durand-Gasselin B, Lhote F, Jarrousse B, Callard P. Treatment of glomerulonephritis in microscopic polyangiitis and Churg–Strauss syndrome. Indications of plasma exchanges, Meta-analysis of 2 randomized studies on 140 patients, 32 with glomerulonephritis. Ann Med Interne (Paris). 1997;148(3):198–204.Google Scholar
  36. 36.
    Jayne DRW, Gaskin G, Rasmussen N, et al. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. 2007;18(7):2180–8.CrossRefGoogle Scholar
  37. 37.
    Stone JH, Uhlfelder ML, Hellmann DB, Crook S, Bedocs N-M, Hoffman GS. Etanercept combined with conventional treatment in Wegener’s granulomatosis: a six-month open-label trial to evaluate safety. Arthritis Rheum. 2001;44(5):1149–54.CrossRefGoogle Scholar
  38. 38.
    Josselin L, Mahr A, Cohen P, et al. Infliximab efficacy and safety against refractory systemic necrotising vasculitides: long-term follow-up of 15 patients. Ann Rheum Dis. 2008;67(9):1343–6.CrossRefGoogle Scholar
  39. 39.
    Wegener’s Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener’s granulomatosis. N Engl J Med. 2005;352(4):351–61.CrossRefGoogle Scholar
  40. 40.
    Voswinkel J, Mueller A, Kraemer JA, et al. B lymphocyte maturation in Wegener’s granulomatosis: a comparative analysis of VH genes from endonasal lesions. Ann Rheum Dis. 2006;65(7):859–64.CrossRefGoogle Scholar
  41. 41.
    Charles P, Néel A, Tieulié N, et al. Rituximab for induction and maintenance treatment of ANCA-associated vasculitides: a multicentre retrospective study on 80 patients. Rheumatology (Oxford). 2014;53(3):532–9.CrossRefGoogle Scholar
  42. 42.
    Langford CA, Monach PA, Specks U, et al. An open-label trial of abatacept (CTLA4-Ig) in non-severe relapsing granulomatosis with polyangiitis (Wegener’s). Ann Rheum Dis. 2014;73(7):1376–9.CrossRefGoogle Scholar
  43. 43.
    Tatsis E, Schnabel A, Gross WL. Interferon-alpha treatment of four patients with the Churg–Strauss syndrome. Ann Intern Med. 1998;129(5):370–4.CrossRefGoogle Scholar
  44. 44.
    Metzler C, Csernok E, Gross WL, Hellmich B. Interferon-alpha for maintenance of remission in Churg–Strauss syndrome: a long-term observational study. Clin Exp Rheumatol. 2010;28(Suppl 57):24–30.PubMedGoogle Scholar
  45. 45.
    Seeliger B, Förster M, Happe J, et al. Interferon-α for induction and maintenance of remission in eosinophilic granulomatosis with polyangiitis: a single-center retrospective observational cohort study. J Rheumatol. 2017;44(6):806–14.CrossRefGoogle Scholar
  46. 46.
    Soresi S, Togias A. Mechanisms of action of anti-immunoglobulin E therapy. Allergy Asthma Proc. 2006;27(Suppl 1):S15–23.PubMedGoogle Scholar
  47. 47.
    Jachiet M, Samson M, Cottin V, et al. Anti-IgE monoclonal antibody (omalizumab) in refractory and relapsing eosinophilic granulomatosis with polyangiitis (Churg–Strauss): data on seventeen patients. Arthritis Rheumatol. 2016;68(9):2274–82.CrossRefGoogle Scholar
  48. 48.
    Detoraki A, Capua LD, Varricchi G, Genovese A, Marone G, Spadaro G. Omalizumab in patients with eosinophilic granulomatosis with polyangiitis: a 36-month follow-up study. J Asthma. 2016;53(2):201–6.CrossRefGoogle Scholar
  49. 49.
    Giavina-Bianchi P, Giavina-Bianchi M, Agondi R, Kalil J. Administration of anti-IgE to a Churg–Strauss syndrome patient. Int Arch Allergy Immunol. 2007;144(2):155–8.CrossRefGoogle Scholar
  50. 50.
    Pabst S, Tiyerili V, Grohé C. Apparent response to anti-IgE therapy in two patients with refractory "forme fruste" of Churg–Strauss syndrome. Thorax. 2008;63(8):747–8.CrossRefGoogle Scholar
  51. 51.
    Lau EMT, Cooper W, Bye PT, Yan K. Difficult asthma and Churg–Strauss-like syndrome: a cautionary tale. Respirology. 2011;16(1):180–1.CrossRefGoogle Scholar
  52. 52.
    Iglesias E, Camacho Lovillo M, Delgado Pecellín I, et al. Successful management of Churg–Strauss syndrome using omalizumab as adjuvant immunomodulatory therapy: first documented pediatric case. Pediatr Pulmonol. 2014;49(3):E78–81.CrossRefGoogle Scholar
  53. 53.
    Graziani A, Quercia O, Girelli F, et al. Omalizumab treatment in patient with severe asthma and eosinophilic granulomatosis with polyangiitis. A case report. Eur Ann Allergy Clin Immunol. 2014;46(6):226–8.PubMedGoogle Scholar
  54. 54.
    Aguirre-Valencia D, Posso-Osorio I, Bravo J-C, Bonilla-Abadía F, Tobón GJ, Cañas CA. Sequential rituximab and omalizumab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome). Clin Rheumatol. 2017;36(9):2159–62.CrossRefGoogle Scholar
  55. 55.
    Nazir S, Tachamo N, Fareedy SB, Khan MS, Lohani S. Omalizumab-associated eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome). Ann Allergy Asthma Immunol. 2017;118(3):372–4.CrossRefGoogle Scholar
  56. 56.
    Bekçibaşı M, Barutçu S, Çelen MK, Dayan S, Hoşoğlu S. Churg–Strauss syndrome occurring during omalizumab treatment. Eur J Rheumatol. 2015;2(3):129–30.CrossRefGoogle Scholar
  57. 57.
    Szwarc D, Veillon F, Moser T, Averous G, De Blay F, Riehm S. Churg–Strauss syndrome under omalizumab treatment: a rare visceral manifestation. J Radiol. 2009;90(11 Pt 1):1737–9.CrossRefGoogle Scholar
  58. 58.
    Wechsler ME, Wong DA, Miller MK, Lawrence-Miyasaki L. Churg–Strauss syndrome in patients treated with omalizumab. Chest. 2009;136(2):507–18.CrossRefGoogle Scholar
  59. 59.
    Mepolizumab: 240563, anti-IL-5 monoclonal antibody—GlaxoSmithKline, anti-interleukin-5 monoclonal antibody—GlaxoSmithKline, SB 240563. Drugs R D. 2008;9(2):125–30.Google Scholar
  60. 60.
    Leckie MJ, ten Brinke A, Khan J, et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet. 2000;356(9248):2144–8.CrossRefGoogle Scholar
  61. 61.
    Keating GM. Mepolizumab: first global approval. Drugs. 2015;75(18):2163–9.CrossRefGoogle Scholar
  62. 62.
    Kahn J-E, Grandpeix-Guyodo C, Marroun I, et al. Sustained response to mepolizumab in refractory Churg–Strauss syndrome. J Allergy Clin Immunol. 2010;125(1):267–70.CrossRefGoogle Scholar
  63. 63.
    Kim S, Marigowda G, Oren E, Israel E, Wechsler ME. Mepolizumab as a steroid-sparing treatment option in patients with Churg–Strauss syndrome. J Allergy Clin Immunol. 2010;125(6):1336–43.CrossRefGoogle Scholar
  64. 64.
    Moosig F, Gross WL, Herrmann K, Bremer JP, Hellmich B. Targeting interleukin-5 in refractory and relapsing Churg–Strauss syndrome. Ann Intern Med. 2011;155(5):341–3.CrossRefGoogle Scholar
  65. 65.
    Herrmann K, Gross WL, Moosig F. Extended follow-up after stopping mepolizumab in relapsing/refractory Churg–Strauss syndrome. Clin Exp Rheumatol. 2012;30(Suppl 70):S62–5.PubMedGoogle Scholar
  66. 66.
    Wechsler ME, Akuthota P, Jayne D, et al. Mepolizumab or placebo for eosinophilic granulomatosis with polyangiitis. N Engl J Med. 2017;376(20):1921–32.CrossRefGoogle Scholar
  67. 67.
    Umezawa N, Kohsaka H, Nanki T, et al. Successful treatment of eosinophilic granulomatosis with polyangiitis (EGPA; formerly Churg–Strauss syndrome) with rituximab in a case refractory to glucocorticoids, cyclophosphamide, and IVIG. Mod Rheumatol. 2014;24(4):685–7.CrossRefGoogle Scholar
  68. 68.
    Pepper RJ, Fabre MA, Pavesio C, et al. Rituximab is effective in the treatment of refractory Churg–Strauss syndrome and is associated with diminished T-cell interleukin-5 production. Rheumatology (Oxford). 2008;47(7):1104–5.CrossRefGoogle Scholar
  69. 69.
    Thiel J, Hässler F, Salzer U, Voll RE, Venhoff N. Rituximab in the treatment of refractory or relapsing eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome). Arthritis Res Ther. 2013;15(5):R133.CrossRefGoogle Scholar
  70. 70.
    Mohammad AJ, Hot A, Arndt F, et al. Rituximab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg–Strauss). Ann Rheum Dis. 2016;75(2):396–401.CrossRefGoogle Scholar
  71. 71.
    Fanouriakis A, Kougkas N, Vassilopoulos D, Fragouli E, Repa A, Sidiropoulos P. Rituximab for eosinophilic granulomatosis with polyangiitis with severe vasculitic neuropathy: case report and review of current clinical evidence. Semin Arthritis Rheum. 2015;45(1):60–6.CrossRefGoogle Scholar
  72. 72.
    Specks U, Merkel PA, Seo P, et al. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med. 2013;369(5):417–27.CrossRefGoogle Scholar
  73. 73.
    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(1):36–44.CrossRefGoogle Scholar
  74. 74.
    Pagnoux C, Mahr A, Hamidou MA, et al. Azathioprine or methotrexate maintenance for ANCA-Associated vasculitis. N Engl J Med. 2008;359(26):2790–803.CrossRefGoogle Scholar
  75. 75.
    Hiemstra TF, Walsh M, Mahr A, et al. Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial. JAMA. 2010;304(21):2381–8.CrossRefGoogle Scholar
  76. 76.
    Guillevin L, Pagnoux C, Karras A, et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med. 2014;371(19):1771–80.CrossRefGoogle Scholar
  77. 77.
    Rituximab versus azathioprine to maintain remission of ANCA-associated vasculitides (MAINRITSAN): follow-up at 60 months. ACR meeting. Abstracts. or pubmed. PMID: 29724729.CrossRefGoogle Scholar
  78. 78.
    Karras A, Pagnoux C, Haubitz M, et al. Randomised controlled trial of prolonged treatment in the remission phase of ANCA-associated vasculitis. Ann Rheum Dis. 2017;76(10):1662–8.CrossRefGoogle Scholar
  79. 79.
    Charles P, Terrier B, Cohen P, et al. Comparison of systematic vs individually tailored rituximab regimen to maintain ANCA-associated–vasculitis remission: results of a prospective, randomized–controlled, phase 3 trial [Internet]. ACR Meeting. Abstracts.
  80. 80.
    Leib ES, Restivo C, Paulus HE. Immunosuppressive and corticosteroid therapy of polyarteritis nodosa. Am J Med. 1979;67(6):941–7.CrossRefGoogle Scholar
  81. 81.
    Luqmani RA, Bacon PA, Moots RJ, et al. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM. 1994;87(11):671–8.PubMedGoogle Scholar
  82. 82.
    Guillevin L, Lhote F, Gayraud M, et al. Prognostic factors in polyarteritis nodosa and Churg–Strauss syndrome. A prospective study in 342 patients. Medicine (Baltimore). 1996;75(1):17–28.CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Loïc Guillevin
    • 1
    Email author
  • Loïc Raffray
    • 2
  • Yann Nguyen
    • 1
  • Benjamin Chaigne
    • 1
  • Benjamin Terrier
    • 1
  1. 1.Department of Internal Medicine, Referral Center for Rare Systemic and Autoimmune Diseases, Hôpital CochinUniversité Paris DescartesParisFrance
  2. 2.Department of Internal MedicineFélix-Guyon University Hospital of La RéunionSaint Denis, Réunion IslandFrance

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