Guidelines of treatment of patients with ANCA-associated vasculitis


DOI: https://dx.doi.org/10.18565/therapy.2021.6.72-80

Bulanov N.M., Tao E.A., Novikov P.I., Smirnova I.G., Moiseev S.V.

1) I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University); 2) M.V. Lomonosov Moscow State University
Abstract. ANCA-associated vasculites (AAV) refer to systemic autoimmune diseases that are characterized by necrotizing, low-immune inflammation of the walls of predominantly small vessels and the circulation of antibodies to the cytoplasm of neutrophils aimed against myeloperoxidase or proteinase-3. The most common target organs that determine the severity of the disease and the patient’s prognosis are lungs and kidneys. Published in recent years research works allow us to revise the traditional ideas about the optimal AAV treatment approaches. Among the main tendencies one can mark a decrease in the volume and duration of induction therapy with glucocorticosteroids and cytostatics, as well as the possibility of adjusting therapy schemes based on the severity of the course of the disease and the serological profile of the patient. The article presents the modern principles of AAV therapy based on the clinical guidelines of the European Society of Rheumatology and the European Association of Nephrology.
Keywords: ANCA-associated vasculitis, plasma exchange, azathioprine, glucocorticosteroids, mycophenolate mofetil, rituximab, cyclophosphamide
Read entire article

Literature


  1. Jennette J.C., Falk R.J., Bacon P.A. et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013; 65(1): 1–11. doi: 10.1002/art.37715.

  2. Lyons P.A., Rayner T., Trivedi S. et al. Genetically distinct subsets within ANCA-associated vasculitis. N Engl J Med. 2012; 367(3): 214–23. doi: 10.1056/NEJMoa1108735.

  3. Xie G., Roshandel D., Sherva R. et al. Association of granulomatosis with polyangiitis (Wegener’s) with HLA-DPB1*04 and SEMA6A gene variants: Evidence from genome-wide analysis. Arthritis Rheum. 2013; 65(9): 2457–68. doi: 10.1002/art.38036.

  4. Tadema H., Abdulahad W., Lepse N. et al. Bacterial DNA motifs trigger ANCA production in ANCA-associated vasculitis in remission. Rheumatology (Oxford). 2011; 50(4): 689–96. doi: 10.1093/rheumatology/keq375.

  5. Gomez-Puerta J.A., Gedmintas L., Costenbader K.H. The association between silica exposure and development of ANCA-associated vasculitis: Systematic review and meta-analysis. Autoimmun Rev. 2013; 12(12): 1129–35. doi: 10.1016/j.autrev.2013.06.016.

  6. Rozina T., Fastovets S., Lee O. et al. D-penicillamine-induced autoimmune disorders. Dig Liver Dis. 2019; 51(12): 1741–42. doi: 10.1016/j.dld.2019.08.025.

  7. Watts R.A., Mahr A., Mohammad A.J. et al. Classification, epidemiology and clinical subgrouping of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Nephrol Dial Transplant. 2015; 30 Suppl 1: i14–22. doi: 10.1093/ndt/gfv022.

  8. de Lind van Wijngaarden R.A.F., Robert A., Hauer H. et al. Clinical and histologic determinants of renal outcome in ANCA-associated vasculitis: A prospective analysis of 100 patients with severe renal involvement. J Am Soc Nephrol. 2006; 17(8): 2264–74. doi: 10.1681/ASN.2005080870.

  9. Томилина Н.А., Бирюкова Л.С., Фролова Н.Ф. с соавт. Клинико-морфологическая характеристика и прогноз разных гистоморфологических вариантов быстропрогрессирующего гломерулонефрита, ассоциированного с АНЦА-васкулитом. Нефрология и диализ. 2017; 4: 466–477. [Tomilina N.A., Biryukova L.S., Frolova N.D. et al. Clinical and morphological characteristics and prognosis of different histomorphological variants of rapidly progressing glomerulonephritis associated with ANCA-vasculitis. Nefrologiya i dializ = Nephrology and Dialysis. 2017; 4: 466–477 (In Russ.)].

  10. Буланов Н.М., Моисеев С.В., Новиков П.И. с соавт. Поражение почек при различных вариантах АНЦА-ассоциированных васкулитов. Клиническая фармакология и терапия. 2016; 5: 23–29. [Bulanov N.M., Moiseev S.V., Novikov P.I. et al. Kidney damage in different variants of ANCA-associated vasculitis. Klinicheskaya farmakologiya i terapiya = Clinical Pharmacology and Therapy. 2016; 5: 23–29 (In Russ.)].

  11. Yates M., Watts R.A., Bajema I.M. et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis. 2016; 75(9): 1583–94. doi: 10.1136/annrheumdis-2016-209133.

  12. Novack S.N., Pearson C.M. Cyclophosphamide therapy in Wegener’s granulomatosis. N Engl J Med. 1971; 284(17): 938–42. doi: 10.1056/NEJM197104292841703.

  13. Faurschou M., Sorensen I., Mellemkjaer L. et al. Malignancies in Wegener’s granulomatosis: Incidence and relation to cyclophosphamide therapy in a cohort of 293 patients. J Rheumatol. 2008; 35(1): 100–05.

  14. Hoffman G.S., Kerr G.S., Leavitt R.Y. et al. Wegener granulomatosis: An analysis of 158 patients. Ann Intern Med. 1992; 116(6): 488–98. doi: 10.7326/0003-4819-116-6-488.

  15. de Groot K., Harper L., Jayne D. et al. Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis. Ann Intern Med. 2009; 150(10): 670–80. doi: 10.7326/0003-4819-150-10-200905190-00004.

  16. Harper L., Morgan M., 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. doi: 10.1136/annrheumdis-2011-200477.

  17. Stone J.H., Merkel P., Spiera R. et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010; 363(3): 221–32. doi: 10.1056/NEJMoa0909905.

  18. Jones R.B., Tervaert J.W., Hauser T. et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010; 363(3): 211–20. doi: 10.1056/NEJMoa0909169.

  19. Klemmer P.J., Chalermskulrat W., Reif M.S. et al. Plasmapheresis therapy for diffuse alveolar hemorrhage in patients with small-vessel vasculitis. Am J Kidney Dis. 2003; 42(6): 1149–53. doi: 10.1053/j.ajkd.2003.08.015.

  20. Szpirt W.M., Heaf J.G., Petersen J. Plasma exchange for induction and cyclosporine A for maintenance of remission in Wegener’s granulomatosis--a clinical randomized controlled trial. Nephrol Dial Transplant. 2011; 26(1): 206–13. doi: 10.1093/ndt/gfq360.

  21. Jayne D.R.W., 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): 2180–88. doi: 10.1681/ASN.2007010090.

  22. 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(2): 397–402. doi: 10.1038/ki.2013.131.

  23. Walsh M., Merkel P., Peh C. et al. Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis. N Engl J Med. 2020; 382(7): 622–31. doi: 10.1056/NEJMoa1803537.

  24. De Groot K., Rasmussen N., Bacon P. 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): 2461–69. doi: 10.1002/art.21142.

  25. Faurschou M., Westman K., Rasmussen N. et al. Brief report: Long-term outcome of a randomized clinical trial comparing methotrexate to cyclophosphamide for remission induction in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2012; 64(10): 3472–77. doi: 10.1002/art.34547.

  26. Tuin J., Stassen P., Bogdan D. et al. Mycophenolate mofetil versus cyclophosphamide for the induction of remission in nonlife-threatening relapses of antineutrophil cytoplasmic antibody-associated vasculitis. Clin J Am Soc Nephrol. 2019; 14(7): 1021–28. doi: 10.2215/CJN.11801018.

  27. Jones R.B., Hiemstra T., 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. doi: 10.1136/annrheumdis-2018-214245.

  28. Unizony S., Villarreal M., Miloslavsky E. et al. Clinical outcomes of treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis based on ANCA type. Ann. Rheum. Dis. 2016; 75(6): 1166–69. doi: 10.1136/annrheumdis-2015-208073.

  29. Miloslavsky E.M., Specks U., Merkel P. et al. Outcomes of nonsevere relapses in antineutrophil cytoplasmic antibody-associated vasculitis treated with glucocorticoids. Arthritis Rheumatol. 2015; 67(6): 1629–36. doi: 10.1002/art.39104.

  30. Hellmich B., Flossmann O., Gross W. 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(5): 605–17. doi: 10.1136/ard.2006.062711.

  31. Miloslavsky E.M., Specks U., Merkel P. et al. Clinical outcomes of remission induction therapy for severe antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2013; 65(9): 2441–49. doi: 10.1002/art.38044.

  32. Pullerits R., Ljevak M., Vikgren J. et al. Off-trial evaluation of the B cell-targeting treatment in the refractory cases of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis: Long-term follow-up from a single centre. Scand J Immunol. 2012; 76(4): 411–20. doi: 10.1111/j.1365-3083.2012.02747.x.

  33. Seror R., Pagnoux C., Ruivard M. et al. Treatment strategies and outcome of induction-refractory Wegener’s granulomatosis or microscopic polyangiitis: analysis of 32 patients with first-line induction-refractory disease in the WEGENT trial. Ann Rheum Dis. 2010; 69(12): 2125–30. doi: 10.1136/ard.2010.131953.

  34. Talar-Williams C., Hijazi Y., Walther M. et al. Cyclophosphamide-induced cystitis and bladder cancer in patients with Wegener granulomatosis. Ann Intern Med. 1996; 124(5): 477. doi: 10.7326/0003-4819-124-5-199603010-00003.

  35. Knight A., Askling J., Granath F. et al. Urinary bladder cancer in Wegener’s granulomatosis: risks and relation to cyclophosphamide. Ann Rheum Dis. 2004 ;63(10): 1307–11. doi: 10.1136/ard.2003.019125.

  36. 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. doi: 10.1056/NEJMoa020286.

  37. Anstey A., Lennard L., Mayou S. et al. Pancytopenia related to azathioprine – an enzyme deficiency caused by a common genetic polymorphism: A review. J R Soc Med. 1992; 85(12): 752–56.

  38. 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. doi: 10.1056/NEJMoa1404231.

  39. Smith R., Jayne D., Merkel P. A randomized, controlled trial of rituximab versus azathioprine after induction of remission with rituximab for patients with ANCA-associated vasculitis and relapsing disease – ACR meeting abstracts. Arthritis Rheumatol. 2019; 71(supl 10).

  40. Charles P., Terrier B., Perrodeau E. 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(8): 1143–49. doi: 10.1136/annrheumdis-2017-212878.

  41. Hiemstra T.F., Walsh M., Mahr A. et al. Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis. JAMA. 2010; 304(21): 2381. doi: 10.1001/jama.2010.1658.

  42. Langford C.A., Talar-Williams C., Barron K. 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(6): 463–69. doi: 10.1016/s0002-9343(03)00077-9.

  43. Puechal X., Pagnoux C., Rerrodeau E. et al. Long-term outcomes among participants in the WEGENT trial of remission-maintenance therapy for granulomatosis with polyangiitis (Wegener’s) or microscopic polyangiitis. Arthritis Rheumatol. 2016; 68(3): 690–701. doi: 10.1002/art.39450.

  44. Springer J., Nutter B., Langford C. et al. Granulomatosis with polyangiitis (Wegener’s): Impact of maintenance therapy duration. Medicine (Baltimore). 2014; 93(2): 82–90. doi: 10.1097/MD.0000000000000020.

  45. 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): 1662–68. doi: 10.1136/annrheumdis-2017-211123.

  46. Charles P., Perrodeau E., Samson M. et al. Long-term rituximab use to maintain remission of antineutrophil cytoplasmic antibody-associated vasculitis. Ann Intern Med. 2020; 173(3): 179–87. doi: 10.7326/M19-3827.

  47. Walsh M., Merkel P., Mahr A. et al. Effects of duration of glucocorticoid therapy on relapse rate in antineutrophil cytoplasmic antibody-associated vasculitis: A meta-analysis. Arthritis Care Res (Hoboken). 2010; 62(8): 1166–73. doi: 10.1002/acr.20176.

  48. Pagnoux C., Quemeneur 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. doi: 10.1002/art.39011.

  49. Mahr A., Girard T., Agher R. et al. Analysis of factors predictive of survival based on 49 patients with systemic Wegener’s granulomatosis and prospective follow-up. Rheumatology (Oxford). 2001; 40(5): 492–98. doi: 10.1093/rheumatology/40.5.492.

  50. Jeffs L.S., Peh C., Jase M. et al. Randomized trial investigating the safety and efficacy of influenza vaccination in patients with antineutrophil cytoplasmic antibody-associated vasculitis. Nephrology (Carlton). 2015; 20(5): 343–51. doi: 10.1111/nep.12416.

  51. Stassen P.M., Sanders J., Kallenberg C. et al. Influenza vaccination does not result in an increase in relapses in patients with ANCA-associated vasculitis. Nephrol Dial Transplant. 2007; 23(2): 654–58. doi: 10.1093/ndt/gfm640.

  52. Rondaan C., Furer V., Heijstek M. et al. Efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases: a systematic literature review for the 2019 update of EULAR recommendations. RMD Open. 2019; 5(2): e001035. doi: 10.1136/rmdopen-2019-001035.

  53. Lee J.J., Pope J.E. A meta-analysis of the risk of venous thromboembolism in inflammatory rheumatic diseases. Arthritis Res Ther. 2014; 16(5): 435. doi: 10.1186/s13075-014-0435-y.

  54. Yamada Y., Harada M., Hara Y. et al. Efficacy of plasma exchange for antineutrophil cytoplasmic antibody-associated systemic vasculitis: a systematic review and meta-analysis. Arthritis Res Ther. 2021; 23(1): 28. doi: 10.1186/s13075-021-02415-z.

  55. Smith R., Jones R., Specks U. et al. Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis. Ann Rheum Dis. 2020; 79(9): 1243–49. doi: 10.1136/annrheumdis-2019-216863.


About the Autors

Nikolai M. Bulanov, PhD, associate professor of the Department of internal, occupational diseases and rheumatology, I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University). Address: 119021, Moscow, 11/5 Rossolimo Str. Tel.: +7 (499) 248-53-33. E-mail: nmbulanov@gmail.com. ORCID: 0000-0002-3989-2590
Ekaterina A. Tao, PhD, assistant of the Department of internal, occupational diseases and rheumatology, I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University). Address: 119021, Moscow, 11/5 Rossolimo Str. Tel.: +7 (499) 248-53-33. E-mail: karovaikinaea@gmail.com. ORCID: 0000-0002-0621-7054
Pavel I. Novikov, PhD, head of the Department of rheumatology of the clinic of nephrology, rheumatology and occupational pathology named after E.A.Tareev of the university clinical hospital No. 3, I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University). Address: 119021, Moscow, 11/5 Rossolimo Str. Tel.: +7 (499) 248-53-33. E-mail: novikov-pavel@mail.ru. ORCID: 0000-0003-0148-5655
Irina G. Smirnova, postgraduate student of the Department of internal, occupational diseases and rheumatology, I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University). Address: 119021, Moscow, 11/5 Rossolimo Str. Tel.: +7 (499) 248-53-33. E-mail: mailbox.smirnova@gmail.com. ORCID: 0000-0001-9930-0879
Sergey V. Moiseev, MD, professor, head of the Department of internal, occupational diseases and rheumatology, I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University), professor of the Department of internal diseases of the faculty of fundamental medicine, M.V. Lomonosov Moscow State University. Address: 119021, Moscow, 11/5 Rossolimo Str. Tel.: +7 (499) 248-53-33. E-mail: avt420034@gmail.com. ORCID: 0000-0002-7232-4640


Similar Articles

Back to Content

Бионика Медиа