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Update on the Treatment of Granulomatosis with Polyangiitis (Wegener’s)

  • Vascular Disease (H Gornik and E Kim, Section Editors)
  • Published:
Current Treatment Options in Cardiovascular Medicine Aims and scope Submit manuscript

Opinion statement

Granulomatosis with polyangiitis (Wegener’s) (GPA), formerly known as Wegener’s granulomatosis, is a systemic vasculitis characterized by involvement of the upper airways, lungs, and kidneys. GPA shares many features with microscopic polyangiitis (MPA), so much so that recent trials have included both vasculitides. This article focuses on GPA only, as complete management includes modalities that are unique to this disease. The current treatment of GPA is stratified based on severity. For those patients who have active but non-severe GPA and do not have contraindications, methotrexate and glucocorticoids can induce and maintain remission. For patients with severe disease, options include glucocorticoids combined with either cyclophosphamide or rituximab. When cyclophosphamide is used, it is given for 3 to 6 months, after which time it is stopped and switched to methotrexate or azathioprine for remission maintenance. In randomized trials, rituximab was found to be as effective as cyclophosphamide to induce remission of severe active GPA. Given the recency of experience with rituximab, there remain a number of questions regarding relapse rate, use of repeat courses, long-term toxicity, and combination with maintenance agents. Until these questions are answered, the choice of whether to use cyclophosphamide or rituximab must be decided between the patient and physician. For patients with relapsing disease who have had prior cyclophosphamide exposure, rituximab is an excellent option. In newly diagnosed patients, the extensive experience with cyclophosphamide and its side effect profile must be weighed against these factors with rituximab. There has been limited experience with rituximab in patients with alveolar hemorrhage requiring mechanical ventilation or rapidly progressive glomerulonephritis requiring dialysis, as these patients were excluded from the largest randomized trial. Until such data become available, cyclophosphamide remains the agent with which there has been the greatest experience for efficacy in these settings.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Walton E. Giant cell granuloma of the respiratory tract (Wegener's Granulomatosis). Brit Med J. 1958;2:265–70.

    Article  PubMed  CAS  Google Scholar 

  2. Hollander D, Manning RT. The use of alkylating agents in the treatment of Wegener's granulomatosis. Ann Intern Med. 1967;67:393–8.

    PubMed  CAS  Google Scholar 

  3. Fauci A, Wolff S. Wegener's granulomatosis: studies in eighteen patients and a review of the literature. Medicine. 1973;52:535–61.

    Article  PubMed  CAS  Google Scholar 

  4. Fauci A, Haynes B, Katz P, Wolff S. Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med. 1983;98:76–85.

    PubMed  CAS  Google Scholar 

  5. Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992;116:488–98.

    PubMed  CAS  Google Scholar 

  6. 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;52:2461–9.

    Article  PubMed  Google Scholar 

  7. Langford CA, Talar-Williams C, Barron KS, et al. A staged approach to the treatment of Wegener's granulomatosis: induction of remission with glucocorticoids and daily cyclophosphamide switching to methotrexate for remission maintenance. Arthritis Rheum. 1999;42:2666–73.

    Article  PubMed  CAS  Google Scholar 

  8. 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  PubMed  CAS  Google Scholar 

  9. 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;304:2381–8.

    Article  PubMed  CAS  Google Scholar 

  10. Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363:221–32. This randomized blinded trial of 197 patients compared rituximab to cyclophosphamide for remission induction of severe GPA and MPA.

    Article  PubMed  CAS  Google Scholar 

  11. Jones RB, Tervaert JW, Hauser T, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010;363:211–20.

    Article  PubMed  CAS  Google Scholar 

  12. Holle JU, Gross WL, Latza U, et al. Improved outcome in 445 patients with Wegener's granulomatosis in a German vasculitis center over four decades. Arthritis Rheum. 2011;63:257–66.

    Article  PubMed  Google Scholar 

  13. de Groot K, Harper L, Jayne DR, et al. Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med. 2009;150:670–80.

    PubMed  Google Scholar 

  14. Talar-Williams C, Hijazi YM, Walther MM, et al. Cyclophosphamide-induced cystitis and bladder cancer in patients with Wegener granulomatosis. Ann Intern Med. 1996;124:477–84.

    PubMed  CAS  Google Scholar 

  15. Le Guenno G, Mahr A, Pagnoux C, et al. Incidence and predictors of urotoxic adverse events in cyclophosphamide-treated patients with systemic necrotizing vasculitides. Arthritis Rheum. 2011;63:1435–45.

    Article  PubMed  Google Scholar 

  16. Monach PA, Arnold LM, Merkel PA. Incidence and prevention of bladder toxicity from cyclophosphamide in the treatment of rheumatic diseases: a data-driven review. Arthritis Rheum. 2010;62:9–21.

    Article  PubMed  CAS  Google Scholar 

  17. Hoffman GS, Leavitt RY, Kerr GS, et al. The treatment of Wegener's granulomatosis with glucocorticoids and methotrexate. Arthritis Rheum. 1992;35:6112–8.

    Google Scholar 

  18. Sneller M, Hoffman G, Talar-Williams C, et al. Analysis of 42 Wegener's granulomatosis patients treated with methotrexate and prednisone. Arthritis Rheum. 1995;38:608–13.

    Article  PubMed  CAS  Google Scholar 

  19. de Groot K, Reinhold-Keller E, Tatsis E, et al. Therapy for the maintenance of remission in sixty-five patients with generalized Wegener's granulomatosis. Methotrexate versus trimethoprim/sulfamethoxazole. Arthritis Rheum. 1996;39:2052–61.

    Article  PubMed  Google Scholar 

  20. Langford CA, Talar-Williams C, Sneller MC. Use of methotrexate and glucocorticoids in the treatment of Wegener's granulomatosis. Long-term renal outcome in patients with glomerulonephritis. Arthritis Rheum. 2000;43:1836–40.

    Article  PubMed  CAS  Google Scholar 

  21. Villa-Forte A, Clark TM, Gomes M, et al. Substitution of methotrexate for cyclophosphamide in Wegener granulomatosis: a 12-year single-practice experience. Medicine (Baltimore). 2007;86:269–77.

    Article  CAS  Google Scholar 

  22. Langford CA, Talar-Williams C, Barron KS, et al. Use of a cyclophosphamide-induction methotrexate-maintenance regimen for the treatment of Wegener's granulomatosis: extended follow-up and rate of relapse. Am J Med. 2003;114:463–9.

    Article  PubMed  CAS  Google Scholar 

  23. Pagnoux C, Mahr A, Hamidou MA, et al. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med. 2008;359:2790–803.

    Article  PubMed  CAS  Google Scholar 

  24. Tukova J, Chladek J, Nemcova D, et al. Methotrexate bioavailability after oral and subcutaneous dministration in children with juvenile idiopathic arthritis. Clin Exp Rheumatol. 2009;27:1047–53.

    PubMed  CAS  Google Scholar 

  25. van Roon EN, van de Laar MA. Methotrexate bioavailability. Clin Exp Rheumatol. 2010;28:S27–32.

    PubMed  Google Scholar 

  26. Langford CA, Talar-Williams C, Sneller MC. Mycophenolate mofetil for remission maintenance in the treatment of Wegener's granulomatosis. Arthritis Rheum. 2004;51:278–83.

    Article  PubMed  CAS  Google Scholar 

  27. Nowack R, Göbel U, Klooker P, et al. Mycophenolate mofetil for maintenance therapy of Wegener's granulomatosis and microscopic polyangiitis: a pilot study in 11 patients with renal involvement. J Am Soc Nephrol. 1999;10:1965–71.

    PubMed  CAS  Google Scholar 

  28. Silva F, Specks U, Kalra S, et al. Mycophenolate mofetil for induction and maintenance of remission in microscopic polyangiitis with mild to moderate renal involvement–a prospective, open-label pilot trial. Clin J Am Soc Nephrol. 2010;5:445–53.

    Article  PubMed  CAS  Google Scholar 

  29. Specks U, Fervenza FC, McDonald TJ, et al. Response of Wegener's granulomatosis to anti-CD20 chimeric monoclonal antibody therapy. Arthritis Rheum. 2001;44:2836–40.

    Article  PubMed  CAS  Google Scholar 

  30. Keogh KA, Wylam ME, Stone JH, et al. Induction of remission by B lymphocyte depletion in eleven patients with refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2005;52:262–8.

    Article  PubMed  Google Scholar 

  31. Keogh KA, Ytterberg SR, Fervenza FC, et al. Rituximab for refractory Wegener's granulomatosis: report of a prospective, open-label pilot trial. Am J Respir Crit Care Med. 2006;173:180–7.

    Article  PubMed  CAS  Google Scholar 

  32. Flossmann O, Berden A, de Groot K, et al. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis. 2011;70:488–94.

    Article  PubMed  Google Scholar 

  33. Jones RB, Ferraro AJ, Chaudhry AN, et al. A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2009;60:2156–68.

    Article  PubMed  CAS  Google Scholar 

  34. Taylor SR, Salama AD, Joshi L, et al. Rituximab is effective in the treatment of refractory ophthalmic Wegener's granulomatosis. Arthritis Rheum. 2009;60:1540–7.

    Article  PubMed  Google Scholar 

  35. Brihaye B, Aouba A, Pagnoux C, et al. Adjunction of rituximab to steroids and immunosuppressants for refractory/relapsing Wegener's granulomatosis: a study on 8 patients. Clin Exp Rheumatol. 2007;25:S23–7.

    PubMed  CAS  Google Scholar 

  36. DeRemee RA, McDonald TJ, Weiland LH. Wegener's granulomatosis: observations on treatment with antimicrobial agents. Mayo Clin Proc. 1985;60:27–32.

    PubMed  CAS  Google Scholar 

  37. Stegeman CA, Cohen Tervaert JW, de Jong PE, et al. Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener's granulomatosis. N Engl J Med. 1996;335:16–20.

    Article  PubMed  CAS  Google Scholar 

  38. Sneller MC, Hoffman GS, Talar-Williams C, et al. An analysis of forty-two Wegener's granulomatosis patients treated with methotrexate and prednisone. Arthritis Rheum. 1995;38:608–13.

    Article  PubMed  CAS  Google Scholar 

  39. Ognibene FP, Shelhamer JH, Hoffman GS, et al. Pneumocystis carinii pneumonia: a major complication of immunosuppressive therapy in patients with Wegener's granulomatosis. Am J Respir Crit Care Med. 1995;151:795–9.

    PubMed  CAS  Google Scholar 

  40. Hernandez-Rodriguez J, Hoffman GS, Koening CL. Surgical interventions and local therapy for Wegener's granulomatosis. Curr Opin Rheumatol. 2010;22:29–36.

    Article  PubMed  Google Scholar 

  41. Langford CA, Sneller MC, Hallahan CW, et al. Clinical features and therapeutic management of subglottic stenosis in patients with Wegener's granulomatosis. Arthritis Rheum. 1996;39:1754–60.

    Article  PubMed  CAS  Google Scholar 

  42. Hoffman GS, Thomas-Golbanov CK, Chan J, et al. Treatment of subglottic stenosis, due to Wegener's granulomatosis, with intralesional corticosteroids and dilation. J Rheumatol. 2003;30:1017–21.

    PubMed  Google Scholar 

  43. Wolter NE, Ooi EH, Witterick IJ. Intralesional corticosteroid injection and dilatation provides effective management of subglottic stenosis in Wegener's granulomatosis. Laryngoscope. 2010;120:2452–5.

    Article  PubMed  Google Scholar 

  44. Walsh M, Catapano F, Szpirt W, et al. Plasma exchange for renal vasculitis and idiopathic rapidly progressive glomerulonephritis: a meta-analysis. Am J Kidney Dis. 2011;57:566–74.

    Article  PubMed  Google Scholar 

  45. Casian A, Jayne D. Plasma exchange in the treatment of Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and renal limited vasculitis. Curr Opin Rheumatol. 2011;23:12–7.

    Article  PubMed  Google Scholar 

  46. Jayne DR, 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;18:2180–8.

    Article  PubMed  CAS  Google Scholar 

  47. Cabral DA, Uribe AG, Benseler S, et al. Classification, presentation, and initial treatment of Wegener's granulomatosis in childhood. Arthritis Rheum. 2009;60:3413–24.

    Article  PubMed  Google Scholar 

  48. Rottem M, Fauci AS, Hallahan CW, et al. Wegener granulomatosis in children and adolescents: clinical presentation and outcome. J Pediatr. 1993;122:26–31.

    Article  PubMed  CAS  Google Scholar 

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Disclosure

C.A. Langford was an investigator in the Rituximab in ANCA-Associated Vasculitis trial (RAVE). Genentech and Bristol-Myers Squibb provided study drug for clinical trials in which Dr. Langford was an investigator.

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  1. Center for Vasculitis Care and Research, Department of Rheumatologic and Immunologic Disease, Cleveland Clinic, 9500 Euclid Avenue, A50, Cleveland, OH, 44195, USA

    Carol A. Langford MD, MHS

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  1. Carol A. Langford MD, MHS
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Correspondence to Carol A. Langford MD, MHS.

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Langford, C.A. Update on the Treatment of Granulomatosis with Polyangiitis (Wegener’s). Curr Treat Options Cardio Med 14, 164–176 (2012). https://doi.org/10.1007/s11936-012-0165-x

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