Experience with rituximab treatment (monoclonal antibodies to B-lymphocyte CD20 receptors) of Wegener's granulematosis patients with renal impairment


Cite item

Full Text

Abstract

Aim. To assess efficacy of rituximab in patients suffering from Wegener's granulematosis (WG) with renal disease.
Material and methods. We analysed clinical laboratory data from 9 WG patients with renal disease treated with rituximab in E.M. Tareev clinic.
Results. The treatment led to a complete remission in 7 (77.8%) patients, a partial remission - in 2 (22.2%) patients. Vasculitis activity regressed including renal damage (a decrease of 24 h proteinurea, enhanced glomerular filtration rate). A prednisolone dose decreased from 38.3 to 10 mg/day (to month 6) and to 7.5 mg/day (to month 12). Non-selective cytostatic drugs were discontinued in all the patients. Recurrences occurred in 3 (33.3%) patients, one with lethal outcome after 6 months of rituximab administration, in two cases one more course of rituximab produced another complete remission. Serious side effects were absent.
Conclusion. Rituximab demonstrated high efficacy in the treatment of WG with renal affection resistant to standard therapy, in multiple side effects of standard immunosuppressive therapy and recurrent course. Rituximab help overcome steroid dependence even at late stages of the disease.

About the authors

Pavel Igorevich Novikov

Email: novikov-pavel@mail.ru

O G Krivosheev

Evgeniya Nikolaevna Semenkova

P I Novikov

I.M. Sechenov First Moscow State Medical University

I.M. Sechenov First Moscow State Medical University

O G Krivosheev

E N Semenkova

I.M. Sechenov First Moscow State Medical University

I.M. Sechenov First Moscow State Medical University

References

  1. Wegener F. Uber eine eigenartige rhinogene granulomatose mit besonderer beteiligung des arteriensystems und der nieren. Beitr. Pathol. 1939; 102: 36-68.
  2. Godman G. C., Churg J. Wegener's granulomatosis; pathology and review of the literature. Arch. Pathol. 1954; 58: 533-553.
  3. Струков А. И., Бадмаева В. В. Отчет о 70 общеинститутских клинико-анатомических конференциях патолого-анатомического отделения I Московского ордена Ленина медицинского института им. И. М. Сеченова за 1948- 1955 гг. Арх. пат. 1957; 19: 77-93.
  4. Reinhold-Keller E., Beuge N., Latza U. et al. An interdisciplinary approach to the care of patients with Wegener's granulomatosis. Long-term outcome in 155 patients. Arthr. and Rheum. 2000; 43: 1021-1032.
  5. Watts R. A., Al-Taiar A., Scott D. G. I., Macgregor A. J. Prevalence and incidence of Wegener's granulomatosis in the UK general practice research database. Arthr. Care Res. 2009; 61: 1412-1416.
  6. Семенкова Е. Н. Системные васкулиты. М.: Медицина; 1988.
  7. Hoffman G. S., Kerr G. S., Leavitt R. Y. et al. Wegener granulomatosis: an analysis of 158 patients. Ann. Intern. Med. 1992; 116: 488-494.
  8. Holle J. U., Gross W. L., Latza U. et al. Improved outcome of 445 Wegener's granulomatosis patients in a German vasculitis center over four decades. Arthr. and Rheum. 2010; Sep 22. [Epub ahead of print].
  9. Petterson E., Sundelin В., Heigl Z. Incidence and outcome of pauci-immune necrotizing and crescentic glomerulonephritis in adult. Clin. Nephrol. 1995; 43: 141-149.
  10. Mukhtyar С., Guillevin L., Cid M. C. et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann. Rheum. Dis. 2009; 68: 310-317.
  11. Mukhtyar C., Flossmann O., Hellmich B. et al. Outcomes from studies of antineutrophil cytoplasm antibody associated vasculitis: a systematic review by the European League Against Rheumatism systemic vasculitis task force. Ann. Rheum. Dis. 2008; 67: 1004-1010.
  12. Клименко С. В., Семенкова Е. Н., Кривошеев О. Г. Применение человеческого иммуноглобулина в комплексном лечении гранулематоза Вегенера. Лечащий врач 2005; 50-52.
  13. Reff M. E., Carner K., Chambers K. S. et al. Depletion of В cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 1994; 83: 435-445.
  14. Arzoo K., Sadeghi S., Liebman H. A. Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20 monoclonal antibody (rituximab). Ann. Rheum. Dis. 2002; 61: 922-924.
  15. Krumbholz M., Specks U., Wick M. et al. BAFF is elevated in the serum of patients with Wegener's granulomatosis. J. Autoimmun. 2005; 25: 298-302.
  16. Voswinkel J., Lamprecht P. Is PR3-ANCA formation initiated in Wegener's granulomatosis lesions? Granulomas as potential lymphoid tissue maintaining autoantibody production. Ann. N. Y. Acad. Sci. 2005; 1051: 12-19.
  17. Falk R. J., Jennette J. C. ANCA are pathogenic: oh yes they are! J. Am. Soc. Nephrol. 2002; 13: 1977-1979.
  18. Heeringa P., Tervaert J. W. Pathophysiology of ANCA-associated vasculitides: are ANCA really pathogenic? Kidney Int. 2004; 65: 1564-1567.
  19. Aouba A., Pagnoux C, Bienvenu B. et al. Analysis of Wegener's granulomatosis responses to rituximab: current evidence and therapeutic prospects. Clin. Rev. Allergy Immunol. 2008; 34: 65-73.
  20. Lovric S., Erdbruegger U. et al. Rituximab as rescue therapy in antineutrophil cytoplasmic antibody-associated vasculitis: a single-centre experience with 15 patients. Nephrol. Dial. Transplant. 2009; 24: 179-185.
  21. Jones R. B., Ferraro A. J., Chaudhry A. N. et al. A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthr. and Rheum. 2009; 60: 2156-2168.
  22. Keogh K. A., Wylam M. E., Stone J. H., Specks U. Induction of remission by В lymphocyte depletion in eleven patients with refractory antineutrophil cytoplasmic antibody-associated vasculitis. Aithr. and Rheum. 2005; 52: 262-268.
  23. Martinez Del Pero M., Chaudhry A., Jones R. B. et al. B-cell depletion with rituximab for refractory head and neck Wegener's granulomatosis: a cohort study. Clin. Otolaryngol. 2009; 34: 328-335.
  24. Specks U., Fervenza F. C., McDonald T. J. et al. Response of Wegener's granulomatosis to anti-CD20 chimeric monoclonal antibody therapy. Arthr. and Rheum. 2001; 44: 2836-2840.
  25. Stasi R., Stipa E., Del Poeta G. et al. Long-term observation of patients with antineutrophil cytoplasmic antibody-associated vasculitis treated with rituximab. Rheumatology 2006; 45: 1432-1436.
  26. Aries P. M., Hellmich В., Voswinkel J. et al. Lack of efficacy of rituximab in Wegener's granulomatosis with refractory granulomatous manifestations. Ann. Rheum. Dis. 2006; 65: 853-858.
  27. Hermle Т., Goestemeyer A.-K., Sweny P., Burns A. Successful therapeutic use of rituximab in refractory Wegener's granulomatosis after renal transplantation. Clin. Nephrol. 2007; 68: 322-326.
  28. 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: 2125-2130.
  29. Wong C. F. Rituximab and antineutrophil cytoplasmic antibody-associated vasculitis. Granulomatous disease more resistant than vasculitis disease? J. Clin. Rheumatol. 2008; 14: 61-64.
  30. Dorner Т., Burmester G. R. New approaches of B-cell-directed therapy: beyond rituximab. Curr. Opin. Rheumatol. 2008; 20: 263-268.
  31. Golbin J. M., Specks U. Targeting В lymphocytes as therapy for ANCA-associated vasculitis. Rheum. Dis. Clin. N. Am. 2007; 33: 741-754.
  32. Hinze C. H., Colbert R. A. B-Cell depletion in Wegener's granulomatosis. Clin. Rev. Allerg. Immunol. 2008; 34: 372-379.
  33. Sneller M. C. Rituximab and Wegener's granulomatosis: Are В cells a target in vasculitis treatment? Arthr. and Rheum. 2005, 52: 1-5.
  34. Мухин Н. А., Семенкова Е. Н., Кривошеев О. Г., Новиков П. И. Применение ритуксимаба при тяжелых АНЦА-ассоциированных системных васкулитах. Клин. нефрология. 2010; 2: 40-45.
  35. Jennette J. C., Falk R. J., Andrassy K. et al. Nomenclature of systemic vasculitides: proposal of an international consensus conference. Arthr. and Rheum. 1994; 37: 187-192.
  36. Leavitt R. Y., Fauci A. S., Bloch D. A. et al. The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis. Arthr. and Rheum. 1990; 33: 1101-1107.
  37. Luqmani R. A., Bacon P. A., Moots R. J. et al. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. Quart. J. Med. 1994; 87: 671-678.
  38. Eriksson P. Nine patients with antineutrophil cytoplasmic antibody-positive vasculitis successfully treated with rituximab. J. Int. Med. 2005; 257: 540-548.
  39. Ferraro A. J., Smith S. W., Neil D., Savage C. O. S. Relapsed Wegener's granulomatosis after rituximab therapy. В cells are present in new pathological lesions despite persistent 'depletion' of peripheral blood. Nephrol. Dial. Transplant. 2008; 23: 3030-3032.
  40. Seo P., Specks U., Keogh K. A. Efficacy of rituximab in limited Wegener's granulomatosis with refractory granulomatous manifestations. J. Rheumatol. 2008; 35: 2017-2023.
  41. Stone J. H., Merkel P. A., Spiera R. et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N. Engl. J. Med. 2010; 363: 221-232.
  42. Jones R. B., Cohen Tervaert J. W., Hauser T. et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N. Engl. J. Med. 2010; 363: 211-220.
  43. Bosch X., Guilabert F., Espinosa G., Mirapeix E. Immunotherapy for antineutrophil cytoplasmic antibody-associated vasculitis: challenging the therapeutic status quo? Trends Immunol. 2008; 29: 280-289.
  44. Lee R. W., D'Cruz D. P. Novel therapies for antineutrophil cytoplasmic antibody-associated vasculitis. Drugs. 2008; 68: 747-770.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2011 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Managing Editor:

  • Tel.: +7 (926) 905-41-26
  • E-mail: e.gorbacheva@ter-arkhiv.ru

 

© 2018-2021 "Consilium Medicum" Publishing house


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies