a reduced-dose glucocorticoid tapering regimen rather than the standard-dosing taper (Grade 1B). Dosing of glucocorticoids is discussed above. (See 'Glucocorticoid dosing and taper' above.) Role of plasma exchange The authors/editors of this topic do not fully agree on the role of plasma exchange among patients with GPA or MPA. All authors agree with the use of plasma exchange in most patients with GPA or MPA who are concomitantly positive for anti-glomerular basement membrane (anti-GBM) autoantibody. Other authors would also offer plasma exchange in patients who present with pulmonary hemorrhage and/or severe active kidney disease with kidney biopsy findings showing active inflammation without significant glomerulosclerosis. (See 'Role of plasma exchange' above.) Maintenance therapy In most patients who achieve remission after induction immunosuppressive therapy, we suggest treatment with rituximab for maintenance of remission (Grade 2C). Azathioprine, methotrexate, and mycophenolate are reasonable alternatives and may be preferred based on other patient-specific factors. Maintenance therapy in patients with newly diagnosed GPA or MPA is usually given for 12 to 24 months after stable remission has been induced. (See 'When to start maintenance therapy' above and 'Choice of maintenance therapy' above and 'Dosing of maintenance therapy' above and 'Duration of maintenance therapy' above.) Non-organ- and non-life-threatening disease Patients with non-organ- or non-life- threatening disease have no evidence of "active glomerulonephritis" (ie, serum creatinine that is stable compared with baseline and no red cell casts or proteinuria) and no organ- threatening or life-threatening manifestations. For patients with non-organ- and non-life- threatening GPA not involving the kidney, we suggest initial therapy with glucocorticoids combined with weekly oral methotrexate rather than glucocorticoids combined with cyclophosphamide, rituximab, or azathioprine (Grade 2C). Rituximab is a reasonable alternative as initial therapy, even in non-organ- and non-life-threatening disease. Azathioprine may be used as an alternative to methotrexate for pregnant patients or https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 33/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate patients for whom methotrexate should be avoided due to moderate to severe kidney function impairment. (See 'Non-organ- and non-life-threatening disease' above.) Monitoring All patients receiving immunosuppressive therapy for GPA or MPA should be closely monitored. Patients with organ- or life-threatening disease are typically admitted to the hospital for treatment with close monitoring of their clinical status and laboratory testing on a daily basis. When the patient's condition is stable enough for discharge from the hospital, we typically schedule follow-up visits every two to four weeks for the first three months. Subsequently, the duration between follow-up visits can then be extended to every two to three months. The goal of these visits is to evaluate the patient's response to therapy and the toxicity of the regimen. (See 'Monitoring the response to therapy' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Stone JH, Hoffman GS, Merkel PA, et al. A disease-specific activity index for Wegener's granulomatosis: modification of the Birmingham Vasculitis Activity Score. International Network for the Study of the Systemic Vasculitides (INSSYS). Arthritis Rheum 2001; 44:912. 2. Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 1992; 116:488. 3. 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. 4. Mahr AD, Neogi T, Lavalley MP, et al. Assessment of the item selection and weighting in the Birmingham vasculitis activity score for Wegener's granulomatosis. Arthritis Rheum 2008; 59:884. 5. WGET Research Group. Design of the Wegener's Granulomatosis Etanercept Trial (WGET). Control Clin Trials 2002; 23:450. 6. Monti S, Quinn KA, Christensen R, et al. Use and reporting of outcome measures in randomized trials for anti-neutrophil cytoplasmic antibody-associated vasculitis: a systematic literature review. Semin Arthritis Rheum 2020; 50:1314. 7. Rhee RL, Davis JC, Ding L, et al. The Utility of Urinalysis in Determining the Risk of Renal Relapse in ANCA-Associated Vasculitis. Clin J Am Soc Nephrol 2018; 13:251. 8. Delvino P, Sardanelli F, Monti S, et al. Remission and Low Disease Activity in Granulomatosis With Polyangiitis and Microscopic Polyangiitis: Prevalence and Impact on Damage Accrual. https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 34/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate Arthritis Care Res (Hoboken) 2023; 75:1158. 9. Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody- Associated Vasculitis. Arthritis Care Res (Hoboken) 2021; 73:1088. 10. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int 2021; 100:S1. 11. Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody- Associated Vasculitis. Arthritis Rheumatol 2021; 73:1366. 12. Rovin BH, Adler SG, Barratt J, et al. Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases. Kidney Int 2021; 100:753. 13. WALTON EW. Giant-cell granuloma of the respiratory tract (Wegener's granulomatosis). Br Med J 1958; 2:265. 14. Hogan SL, Nachman PH, Wilkman AS, et al. Prognostic markers in patients with antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. J Am Soc Nephrol 1996; 7:23. 15. 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. 16. Adu D, Pall A, Luqmani RA, et al. Controlled trial of pulse versus continuous prednisolone and cyclophosphamide in the treatment of systemic vasculitis. QJM 1997; 90:401. 17. Wegener's Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med 2005; 352:351. 18. 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. 19. Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA- associated vasculitis. N Engl J Med 2010; 363:221. 20. Specks U, Merkel PA, Seo P, et al. Efficacy of remission-induction regimens for ANCA- associated vasculitis. N Engl J Med 2013; 369:417. 21. Jones RB, Tervaert JW, Hauser T, et al. Rituximab versus cyclophosphamide in ANCA- associated renal vasculitis. N Engl J Med 2010; 363:211. https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 35/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate 22. Jones RB, Furuta S, Tervaert JW, et al. Rituximab versus cyclophosphamide in ANCA- associated renal vasculitis: 2-year results of a randomised trial. Ann Rheum Dis 2015; 74:1178. 23. Geetha D, Specks U, Stone JH, et al. Rituximab versus cyclophosphamide for ANCA- associated vasculitis with renal involvement. J Am Soc Nephrol 2015; 26:976. 24. Thietart S, Karras A, Augusto JF, et al. Evaluation of Rituximab for Induction and Maintenance Therapy in Patients 75 Years and Older With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. JAMA Netw Open 2022; 5:e2220925. 25. Unizony S, Villarreal M, Miloslavsky EM, et al. Clinical outcomes of treatment of anti- neutrophil cytoplasmic antibody (ANCA)-associated vasculitis based on ANCA type. Ann Rheum Dis 2016; 75:1166. 26. Amudala NA, Boukhlal S, Sheridan B, et al. Obinutuzumab as treatment for ANCA-associated vasculitis. Rheumatology (Oxford) 2022; 61:3814. 27. 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; 40:2187. 28. Haubitz M, Schellong S, G bel U, et al. Intravenous pulse administration of cyclophosphamide versus daily oral treatment in patients with antineutrophil cytoplasmic antibody-associated vasculitis and renal involvement: a prospective, randomized study. Arthritis Rheum 1998; 41:1835. 29. de Groot K, Adu D, Savage CO, EUVAS (European vasculitis study group). The value of pulse cyclophosphamide in ANCA-associated vasculitis: meta-analysis and critical review. Nephrol Dial Transplant 2001; 16:2018. 30. 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; 71:955. 31. Walsh M, Merkel PA, Peh CA, et al. Plasma Exchange and Glucocorticoids in Severe ANCA- Associated Vasculitis. N Engl J Med 2020; 382:622. 32. Miloslavsky EM, Niles JL, Wallace ZS, et al. Reducing glucocorticoid duration in ANCA- associated vasculitis: A pilot trial. Semin Arthritis Rheum 2018; 48:288. 33. Furuta S, Nakagomi D, Kobayashi Y, et al. Effect of Reduced-Dose vs High-Dose Glucocorticoids Added to Rituximab on Remission Induction in ANCA-Associated Vasculitis: A Randomized Clinical Trial. JAMA 2021; 325:2178. https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 36/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate 34. Nezam D, Porcher R, Grolleau F, et al. Kidney Histopathology Can Predict Kidney Function in ANCA-Associated Vasculitides with Acute Kidney Injury Treated with Plasma Exchanges. J Am Soc Nephrol 2022; 33:628. 35. 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. 36. Pusey CD, Rees AJ, Evans DJ, et al. Plasma exchange in focal necrotizing glomerulonephritis without anti-GBM antibodies. Kidney Int 1991; 40:757. 37. Walsh M, Casian A, Flossmann O, et al. Long-term follow-up of patients with severe ANCA- associated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment is unclear. Kidney Int 2013; 84:397. 38. 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. 39. Walsh M, Collister D, Zeng L, et al. The effects of plasma exchange in patients with ANCA- associated vasculitis: an updated systematic review and meta-analysis. BMJ 2022; 376:e064604. 40. Casal Moura M, Irazabal MV, Eirin A, et al. Efficacy of Rituximab and Plasma Exchange in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Severe Kidney Disease. J Am Soc Nephrol 2020; 31:2688. 41. Gallagher H, Kwan JT, Jayne DR. Pulmonary renal syndrome: a 4-year, single-center experience. Am J Kidney Dis 2002; 39:42. 42. Klemmer PJ, Chalermskulrat W, Reif MS, et al. Plasmapheresis therapy for diffuse alveolar hemorrhage in patients with small-vessel vasculitis. Am J Kidney Dis 2003; 42:1149. 43. Hruskova Z, Casian AL, Konopasek P, et al. Long-term outcome of severe alveolar haemorrhage in ANCA-associated vasculitis: a retrospective cohort study. Scand J Rheumatol 2013; 42:211. 44. Cartin-Ceba R, Diaz-Caballero L, Al-Qadi MO, et al. Diffuse Alveolar Hemorrhage Secondary to Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Predictors of Respiratory Failure and Clinical Outcomes. Arthritis Rheumatol 2016; 68:1467. 45. de Luna G, Chauveau D, Aniort J, et al. Plasma exchanges for the treatment of severe systemic necrotizing vasculitides in clinical daily practice: Data from the French Vasculitis Study Group. J Autoimmun 2015; 65:49. 46. Pepper RJ, McAdoo SP, Moran SM, et al. A novel glucocorticoid-free maintenance regimen for anti-neutrophil cytoplasm antibody-associated vasculitis. Rheumatology (Oxford) 2019; https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 37/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate 58:373. 47. Pendergraft WF 3rd, Cortazar FB, Wenger J, et al. Long-term maintenance therapy using rituximab-induced continuous B-cell depletion in patients with ANCA vasculitis. Clin J Am Soc Nephrol 2014; 9:736. 48. McGregor JG, Hogan SL, Kotzen ES, et al. Rituximab as an immunosuppressant in antineutrophil cytoplasmic antibody-associated vasculitis. Nephrol Dial Transplant 2015; 30 Suppl 1:i123. 49. Cortazar FB, Muhsin SA, Pendergraft WF 3rd, et al. Combination Therapy With Rituximab and Cyclophosphamide for Remission Induction in ANCA Vasculitis. Kidney Int Rep 2018; 3:394. 50. Gulati K, Edwards H, Prendecki M, et al. Combination treatment with rituximab, low-dose cyclophosphamide and plasma exchange for severe antineutrophil cytoplasmic antibody- associated vasculitis. Kidney Int 2021; 100:1316. 51. Jayne DRW, Bruchfeld AN, Harper L, et al. Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis. J Am Soc Nephrol 2017; 28:2756. 52. Merkel PA, Niles J, Jimenez R, et al. Adjunctive Treatment With Avacopan, an Oral C5a Receptor Inhibitor, in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. ACR Open Rheumatol 2020; 2:662. 53. Jayne DRW, Merkel PA, Schall TJ, et al. Avacopan for the Treatment of ANCA-Associated Vasculitis. N Engl J Med 2021; 384:599. 54. Pagnoux C, Mahr A, Hamidou MA, et al. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med 2008; 359:2790. 55. Guillevin L, Pagnoux C, Karras A, et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med 2014; 371:1771. 56. 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. 57. Nowack R, G bel 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. 58. Langford CA, Talar-Williams C, Sneller MC. Mycophenolate mofetil for remission maintenance in the treatment of Wegener's granulomatosis. Arthritis Rheum 2004; 51:278. 59. Koukoulaki M, Jayne DR. Mycophenolate mofetil in anti-neutrophil cytoplasm antibodies- associated systemic vasculitis. Nephron Clin Pract 2006; 102:c100. https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 38/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate 60. Ibernon M, Poveda R, Vidaller A, et al. Mycophenolate mofetil in anti-MPO renal vasculitis: an alternative therapy in case of cyclophosphamide or azathioprine toxicity. Clin Nephrol 2008; 69:395. 61. Iatrou C, Zerbala S, Revela I, et al. Mycophenolate mofetil as maintenance therapy in patients with vasculitis and renal involvement. Clin Nephrol 2009; 72:31. 62. Stassen PM, Tervaert JW, Stegeman CA. Induction of remission in active anti-neutrophil cytoplasmic antibody-associated vasculitis with mycophenolate mofetil in patients who cannot be treated with cyclophosphamide. Ann Rheum Dis 2007; 66:798. 63. Smith RM, Jones RB, Guerry MJ, et al. Rituximab for remission maintenance in relapsing antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2012; 64:3760. 64. Cartin-Ceba R, Golbin JM, Keogh KA, et al. Rituximab for remission induction and maintenance in refractory granulomatosis with polyangiitis (Wegener's): ten-year experience at a single center. Arthritis Rheum 2012; 64:3770. 65. Alberici F, Smith RM, Jones RB, et al. Long-term follow-up of patients who received repeat- dose rituximab as maintenance therapy for ANCA-associated vasculitis. Rheumatology (Oxford) 2015; 54:1153. 66. Charles P, Terrier B, Perrodeau , et al. Comparison of individually tailored versus fixed- schedule rituximab regimen to maintain ANCA-associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2). Ann Rheum Dis 2018; 77:1143. 67. Pagnoux C, Guillevin L, French Vasculitis Study Group, MAINRITSAN investigators. Rituximab or azathioprine maintenance in ANCA-associated vasculitis. N Engl J Med 2015; 372:386. 68. Langford CA, Talar-Williams C, Barron KS, Sneller MC. 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. 69. Charles P, Perrodeau , Samson M, et al. Long-Term Rituximab Use to Maintain Remission of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Randomized Trial. Ann Intern Med 2020; 173:179. 70. Sanders JS, de Joode AA, DeSevaux RG, et al. Extended versus standard azathioprine maintenance therapy in newly diagnosed proteinase-3 anti-neutrophil cytoplasmic antibody-associated vasculitis patients who remain cytoplasmic anti-neutrophil cytoplasmic antibody-positive after induction of remission: a randomized clinical trial. Nephrol Dial Transplant 2016; 31:1453. 71. Hogan SL, Nachman PH, Poulton CJ, et al. Understanding Long-term Remission Off Therapy in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Kidney Int Rep 2019; 4:551. https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 39/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate 72. Gapud EJ, Manno R, Seo P, et al. Long-term Clinical Course of Antineutrophil Cytoplasmic Antibody-associated Vasculitis Patients off Maintenance Therapy. Cureus 2018; 10:e2372. 73. 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. 74. 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. 75. Specks U. Methotrexate for Wegener's granulomatosis: what is the evidence? Arthritis Rheum 2005; 52:2237. 76. 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. 77. 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. 78. Mukhtyar C, Guillevin L, Cid MC, et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis 2009; 68:310. 79. Kemna MJ, Damoiseaux J, Austen J, et al. ANCA as a predictor of relapse: useful in patients with renal involvement but not in patients with nonrenal disease. J Am Soc Nephrol 2015; 26:537. 80. G ero lu A, Berden AE, Fiocco M, et al. ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse. PLoS One 2016; 11:e0165402. 81. Fussner LA, Hummel AM, Schroeder DR, et al. Factors Determining the Clinical Utility of Serial Measurements of Antineutrophil Cytoplasmic Antibodies Targeting Proteinase 3. Arthritis Rheumatol 2016; 68:1700. 82. van Dam LS, Dirikgil E, Bredewold EW, et al. PR3-ANCAs predict relapses in ANCA-associated vasculitis patients after rituximab. Nephrol Dial Transplant 2021; 36:1408. 83. 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. 84. McGregor JG, Negrete-Lopez R, Poulton CJ, et al. Adverse events and infectious burden, microbes and temporal outline from immunosuppressive therapy in antineutrophil https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 40/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate cytoplasmic antibody-associated vasculitis with native renal function. Nephrol Dial Transplant 2015; 30 Suppl 1:i171. 85. Niles J. Rituximab in induction therapy for anti-neutrophil cytoplasmic antibody (ANCA) vasculitis. Clin Exp Immunol 2011; 164 Suppl 1:27. 86. 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. 87. 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. 88. Gluth MB, Shinners PA, Kasperbauer JL. Subglottic stenosis associated with Wegener's granulomatosis. Laryngoscope 2003; 113:1304. 89. Congdon D, Sherris DA, Specks U, McDonald T. Long-term follow-up of repair of external nasal deformities in patients with Wegener's granulomatosis. Laryngoscope 2002; 112:731. 90. Langford CA, Kerr GS. Pregnancy in vasculitis. Curr Opin Rheumatol 2002; 14:36. 91. Habib A, MacKay K, Abrons HL. Wegener's granulomatosis complicating pregnancy: presentation of two patients and review of the literature. Clin Nephrol 1996; 46:332. 92. Hruskova Z, Tesar V. Management of Elderly Patients with Rapidly Progressive Glomerulonephritis. Blood Purif 2018; 45:213. 93. Weiner M, Goh SM, Mohammad AJ, et al. Outcome and treatment of elderly patients with ANCA-associated vasculitis. Clin J Am Soc Nephrol 2015; 10:1128. 94. Lionaki S, Hogan SL, Jennette CE, et al. The clinical course of ANCA small-vessel vasculitis on chronic dialysis. Kidney Int 2009; 76:644. 95. Kauffmann M, Bobot M, Robert T, et al. Disease Activity and Adverse Events in Patients with ANCA-Associated Vasculitides Undergoing Long-Term Dialysis. Clin J Am Soc Nephrol 2021; 16:1665. 96. Lee T, Gasim A, Derebail VK, et al. Predictors of treatment outcomes in ANCA-associated vasculitis with severe kidney failure. Clin J Am Soc Nephrol 2014; 9:905. 97. Nachman PH, Segelmark M, Westman K, et al. Recurrent ANCA-associated small vessel vasculitis after transplantation: A pooled analysis. Kidney Int 1999; 56:1544. 98. Gera M, Griffin MD, Specks U, et al. Recurrence of ANCA-associated vasculitis following renal transplantation in the modern era of immunosupression. Kidney Int 2007; 71:1296. 99. Geetha D, Eirin A, True K, et al. Renal transplantation in antineutrophil cytoplasmic antibody- associated vasculitis: a multicenter experience. Transplantation 2011; 91:1370. https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 41/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate 100. Wallace ZS, Wallwork R, Zhang Y, et al. Improved survival with renal transplantation for end- stage renal disease due to granulomatosis with polyangiitis: data from the United States Renal Data System. Ann Rheum Dis 2018; 77:1333. 101. Hruskova Z, Stel VS, Jayne D, et al. Characteristics and Outcomes of Granulomatosis With Polyangiitis (Wegener) and Microscopic Polyangiitis Requiring Renal Replacement Therapy: Results From the European Renal Association-European Dialysis and Transplant Association Registry. Am J Kidney Dis 2015; 66:613. 102. Tang W, Bose B, McDonald SP, et al. The outcomes of patients with ESRD and ANCA- associated vasculitis in Australia and New Zealand. Clin J Am Soc Nephrol 2013; 8:773. 103. Moran S, Little MA. Renal transplantation in antineutrophil cytoplasmic antibody-associated vasculitis. Curr Opin Rheumatol 2014; 26:37. 104. Santoriello D, Bomback AS, Kudose S, et al. Anti-neutrophil cytoplasmic antibody associated glomerulonephritis complicating treatment with hydralazine. Kidney Int 2021; 100:440. 105. 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; 73:1376. 106. Jayne D, Blockmans D, Luqmani R, et al. Efficacy and Safety of Belimumab and Azathioprine for Maintenance of Remission in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Randomized Controlled Study. Arthritis Rheumatol 2019; 71:952. 107. McClure M, Gopaluni S, Jayne D, Jones R. Publisher Correction: B cell therapy in ANCA- associated vasculitis: current and emerging treatment options. Nat Rev Rheumatol 2018; 14:741. 108. Rhee RL, Hogan SL, Poulton CJ, et al. Trends in Long-Term Outcomes Among Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Renal Disease. Arthritis Rheumatol 2016; 68:1711. 109. Wallace ZS, Lu N, Miloslavsky E, et al. Nationwide Trends in Hospitalizations and In-Hospital Mortality in Granulomatosis With Polyangiitis (Wegener's). Arthritis Care Res (Hoboken) 2017; 69:915. 110. Tan JA, Dehghan N, Chen W, et al. Mortality in ANCA-associated vasculitis: ameta-analysis of observational studies. Ann Rheum Dis 2017; 76:1566. 111. Tan JA, Choi HK, Xie H, et al. All-Cause and Cause-Specific Mortality in Patients With Granulomatosis With Polyangiitis: A Population-Based Study. Arthritis Care Res (Hoboken) 2019; 71:155. https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 42/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate 112. Robson J, Doll H, Suppiah R, et al. Damage in the anca-associated vasculitides: long-term data from the European vasculitis study group (EUVAS) therapeutic trials. Ann Rheum Dis 2015; 74:177. 113. Lai QY, Ma TT, Li ZY, et al. Predictors for mortality in patients with antineutrophil cytoplasmic autoantibody-associated vasculitis: a study of 398 Chinese patients. J Rheumatol 2014; 41:1849. 114. King C, Harper L, Little M. The complications of vasculitis and its treatment. Best Pract Res Clin Rheumatol 2018; 32:125. 115. Slot MC, Tervaert JW, Franssen CF, Stegeman CA. Renal survival and prognostic factors in patients with PR3-ANCA associated vasculitis with renal involvement. Kidney Int 2003; 63:670. 116. de Joode AA, Sanders JS, Stegeman CA. Renal survival in proteinase 3 and myeloperoxidase ANCA-associated systemic vasculitis. Clin J Am Soc Nephrol 2013; 8:1709. 117. Bomback AS, Appel GB, Radhakrishnan J, et al. ANCA-associated glomerulonephritis in the very elderly. Kidney Int 2011; 79:757. 118. Thet Z, Lam AK, Ranganathan D, et al. Cancer risks along the disease trajectory in antineutrophil cytoplasmic antibody associated vasculitis. Clin Rheumatol 2020; 39:2501. 119. Rahmattulla C, Berden AE, Wakker SC, et al. Incidence of Malignancies in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Diagnosed Between 1991 and 2013. Arthritis Rheumatol 2015; 67:3270. 120. Shang W, Ning Y, Xu X, et al. Incidence of Cancer in ANCA-Associated Vasculitis: A Meta- Analysis of Observational Studies. PLoS One 2015; 10:e0126016. 121. Wester Trejo MAC, Bajema IM, van Daalen EE. Antineutrophil cytoplasmic antibody- associated vasculitis and malignancy. Curr Opin Rheumatol 2018; 30:44. 122. 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; 70:1415. 123. Mohammad AJ, Segelmark M, Smith R, et al. Severe Infection in Antineutrophil Cytoplasmic Antibody-associated Vasculitis. J Rheumatol 2017; 44:1468. 124. Charlier C, Henegar C, Launay O, et al. Risk factors for major infections in Wegener granulomatosis: analysis of 113 patients. Ann Rheum Dis 2009; 68:658. 125. Goupil R, Brachemi S, Nadeau-Fredette AC, et al. Lymphopenia and treatment-related infectious complications in ANCA-associated vasculitis. Clin J Am Soc Nephrol 2013; 8:416. https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 43/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate 126. Garcia-Vives E, Segarra-Medrano A, Martinez-Valle F, et al. Prevalence and Risk Factors for Major Infections in Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis: Influence on the Disease Outcome. J Rheumatol 2020; 47:407. 127. Little MA, Nightingale P, Verburgh CA, et al. Early mortality in systemic vasculitis: relative contribution of adverse events and active vasculitis. Ann Rheum Dis 2010; 69:1036. 128. van Assen S, Agmon-Levin N, Elkayam O, et al. EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis 2011; 70:414. 129. 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. 130. Weidner S, Geuss S, Hafezi-Rachti S, et al. ANCA-associated vasculitis with renal involvement: an outcome analysis. Nephrol Dial Transplant 2004; 19:1403. 131. Aasar d K, Iversen BM, Hammerstr m J, et al. Wegener's granulomatosis: clinical course in 108 patients with renal involvement. Nephrol Dial Transplant 2000; 15:611. 132. Aasar d K, Bostad L, Hammerstr m J, et al. Renal histopathology and clinical course in 94 patients with Wegener's granulomatosis. Nephrol Dial Transplant 2001; 16:953. 133. Hauer HA, Bajema IM, Van Houwelingen HC, et al. Determinants of outcome in ANCA- associated glomerulonephritis: a prospective clinico-histopathological analysis of 96 patients. Kidney Int 2002; 62:1732. 134. 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. 135. Berden AE, Jones RB, Erasmus DD, et al. Tubular lesions predict renal outcome in antineutrophil cytoplasmic antibody-associated glomerulonephritis after rituximab therapy. J Am Soc Nephrol 2012; 23:313. 136. Mekhail TM, Hoffman GS. Longterm outcome of Wegener's granulomatosis in patients with renal disease requiring dialysis. J Rheumatol 2000; 27:1237. 137. Glassock RJ. Intensive plasma exchange in crescentic glomerulonephritis: help or no help? Am J Kidney Dis 1992; 20:270. 138. Cole E, Cattran D, Magil A, et al. A prospective randomized trial of plasma exchange as additive therapy in idiopathic crescentic glomerulonephritis. The Canadian Apheresis Study Group. Am J Kidney Dis 1992; 20:261. 139. Geffriaud-Ricouard C, No l LH, Chauveau D, et al. Clinical spectrum associated with ANCA of defined antigen specificities in 98 selected patients. Clin Nephrol 1993; 39:125. https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 44/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate 140. Berti A, Matteson EL, Crowson CS, et al. Risk of Cardiovascular Disease and Venous Thromboembolism Among Patients With Incident ANCA-Associated Vasculitis: A 20-Year Population-Based Cohort Study. Mayo Clin Proc 2018; 93:597. 141. Houben E, Penne EL, Voskuyl AE, et al. Cardiovascular events in anti-neutrophil cytoplasmic antibody-associated vasculitis: a meta-analysis of observational studies. Rheumatology (Oxford) 2018; 57:555. 142. Nygaard L, Polcwiartek C, Nelveg-Kristensen KE, et al. Long-term cardiovascular outcomes and temporal trends in patients diagnosed with ANCA-associated vasculitis: a Danish nationwide registry study. Rheumatology (Oxford) 2023; 62:735. 143. Liapi M, Jayne D, Merkel PA, et al. Venous thromboembolism in ANCA-associated vasculitis: a population-based cohort study. Rheumatology (Oxford) 2021; 60:4616. 144. Kronbichler A, Leierer J, Shin JI, et al. Association of Pulmonary Hemorrhage, Positive Proteinase 3, and Urinary Red Blood Cell Casts With Venous Thromboembolism in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Rheumatol 2019; 71:1888. 145. Englund M, Merkel PA, Tomasson G, et al. Comorbidities in Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis versus the General Population. J Rheumatol 2016; 43:1553. 146. Merkel PA, Lo GH, Holbrook JT, et al. Brief communication: high incidence of venous thrombotic events among patients with Wegener granulomatosis: the Wegener's Clinical Occurrence of Thrombosis (WeCLOT) Study. Ann Intern Med 2005; 142:620. 147. Moiseev S, Bulanov N, Crnogorac M, et al. Traditional and Disease-Specific Risk Factors for Cardiovascular Events in ANCA-Associated Vasculitis: A Multinational Retrospective Study. J Rheumatol 2023. Topic 3105 Version 59.0 https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 45/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate GRAPHICS Phase-contrast micrograph showing dysmorphic RBCs in urine sediment Phase-contrast microscopy showing dysmorphic red blood cells (RBCs) and acanthocytes in the urinary sediment of a patient with glomerular hematuria. Acanthocytes (arrows) can be recognized as ring forms with vesicle-shaped protrusions. Courtesy of Juan Carlos Q Velez, MD. Graphic 130438 Version 1.0 https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 46/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate Scanning electron micrograph showing dysmorphic red cells in urine sediment Scanning microscopy showing dysmorphic red cells in a patient with glomerular bleeding. Acanthocytes can be recognized as ring forms with vesicle-shaped protrusions (arrows). Courtesy of Hans K hler, MD. Graphic 62064 Version 3.0 https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 47/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate Initial induction and maintenance therapy in patients with a diagnosis of GPA or MPA This treatment algorithm applies to patients who are not pregnant. Induction therapy in pregnant patients requires modification due to the potential risk of fetal harm associated with some agents. Refer to UpToDate content on initial immunosuppressive therapy in pregnant patients with GPA or MPA. GPA: granulomatosis with polyangiitis; MPA: microscopic polyangiitis; GBM: glomerular basement membrane; ANCA: antineutrophil cytoplasmic autoantibodies; eGFR: estimated glomerular filtration rate. Refer to UpToDate content on the use of rituximab or cyclophosphamide as induction therapy for patients with GPA or MPA who have organ- or life-threatening disease. The role of plasma exchange, in addition to glucocorticoids and either cyclophosphamide or rituximab, among patients with GPA or MPA is controversial. Refer to UpToDate content on plasma exchange in patients with GPA or MPA. https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 48/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate Contraindications to methotrexate include, but are not limited to, heavy alcohol use, chronic liver 2 disease, eGFR <60 mL/min/1.73 m , or evidence of renal vasculitis. Refer to UpToDate content on management of non-organ- and non-life-threatening GPA or MPA. Rituximab is preferred for most patients who achieve remission after induction therapy. Azathioprine, methotrexate, and mycophenolate are reasonable alternatives to rituximab and may be preferred based on other patient-specific factors, such as a prior history of toxicity from a certain drug and/or a comorbid condition that increases the risk of toxicity with a specific agent. Refer to UpToDate content on the choice of maintenance therapy in patients with GPA or MPA. Graphic 111371 Version 3.0 https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy/print 49/55 7/7/23, 11:17 AM Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy - UpToDate Adjusting oral cyclophosphamide dose for adult patients with kidney function impairment Cyclophosphamide (CYC) oral dose Creatinine clearance* (mL/minute) (mg/kg/day) >100 2 50 to 99 1.5 25 to 49 1.2 15 to 24 1 <15 or dialysis 0.8 Initial 2 mg/kg per day dose and adjustments for kidney function impairment are for daily oral administration of "low-dose" cyclophosphamide therapy in rheumatic diseases. For approach, other dose adjustments that may be needed, and duration of therapy, refer to UpToDate topics on the use of cyclophosphamide in rheumatic diseases. CYC: cyclophosphamde; Clcr: creatinine clearance. Can be estimated by using the Cockroft-Gault equation. Clcr = [140-age] * weight (kg)/serum Cr in mg/dL * 72. Multiply result by 0.85 for women. Separate calculators for creatinine clearance using conventional and SI units are available in UpToDate. Usual maximum daily dose is 200 mg. For patients who are overweight or obese, an estimate of ideal or lean body weight is used for estimating Clcr and determining daily CYC weight-based dose. Calculators are available in UpToDate. CYC is variably dialyzable (approximately 20 to 50 percent). Dose may require further adjustment depending upon type of dialysis. For intermittent hemodialysis, give dose after session on dialysis days.