Neutralisation of interferon gamma - a new trend in therapy of rheumatoid arthritis


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Abstract

Aim. To evaluate objectively therapeutic potentialities of a novel method of biological therapy - blocking interferon gamma (IF-γ) - by means of a comparative analysis of using antibodies to IF-g (anti-IF-γ) and tumor necrosis factor alpha (anti-TNF-α) in resistant rheumatoid arthritis (RA). Material and methods. A double blind trial included 55 patients with resistant RA. They received 5 intramuscular injections of anti-IF-y (n = 20), anti-TNF-a (n = 20) and placebo (15 patients). The results were assessed on the treatment day 7 and 28. Results. 16 patients withdrew because of the treatment uneffectiveness (2 from the group on anti-IF-g, 3 - on anti-TNF-α, 11 - on placebo). To the treatment day 28 the patients given anticytokines achieved significant improvement of all clinical indices while placebo group had no improvement. The highest response was observed in the group on anti-IF-γ (ACR 70). As shown by ultrasound investigation, a significant reduction of the synovial membrane thickness took place also in administration of anti-IF-γ Most frequent side effect of the anticytokine therapy was mild dermatitis at injection site on treatment day 8-11. Conclusion. Therapeutic efficacy of anti-IF-γ was comparable with efficacy of anti-TNF-α and even was superior in some aspects. The block of IF-γ holds much promise in the treatment of RA.

About the authors

V A Nasonova

ГУ Институт ревматологии РАМН, Москва

G V Lukina

ГУ Институт ревматологии РАМН, Москва

Ia A Sigidin

ГУ Институт ревматологии РАМН, Москва

References

  1. Skurkovich S. V., Klimova К. G., Eremkina E. I. et al. Immunosuppressive effect of an anti-interferon serum. Nature 1974; 247: 551-552.
  2. Feldmann M., Brennan F. M., Maini R. N. Role of cytokines in rheumatoid arthritis. Ann. Rev. Immunol. 1996; 14: 397-440.
  3. Lipsky P., Heijde van der D., St Clair E. et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. N. Engl. J. Med. 2000; 343: 1594-1602.
  4. Moreland L. W., Schiff M. H., Baumgartner S. W. et al. Etanercept therapy in rheumatoid arthritis. Ann. Intern. Med. 1999; 130: 478-486.
  5. Weinblatt M. E., Keystone E. C., Furst D. E. et al. Long term efficacy and safety of adalimumab plus methotrexate in patients with rheumatoid arthritis: ARMADA 4 year extended study. Ann. Rheum. Dis. 2006; 65 (6): 753-759.
  6. Michaud K., Wolfe F. Reduced mortality among RA patients treated with anti-TNF therapy and methotrexate. Ann. Rheum. Dis. 2005; 64 (suppl. III): 87.
  7. Genant H. K. Interleukin-1 receptor antagonist treatment of rheumatoid arthritis patients. Semin. Arthr. Rheum. 2001; 30 (suppl. 2): 26-32.
  8. Kremer J., Westhovens R., Moreland L. et al. Efficacy and safety of the selective co-stimulation modulator abatacept with methotrexate in treating rheumatoid arthritis. Arthr. and Rheum. 2004; 50 (12): 4095.
  9. Cohen S. В., Emery P., Greenwald M. W. et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy. Arthr. and Rheum. 2006; 54 (9): 2793-2806.
  10. Billiau A. Interferon-Β in autoimmunity. Cytokine Growth Factor Rev. 1996; 7(1): 25-34.
  11. Lotz M. Cytokines and their receptors. In: Koopman W. J., ed. Arthritis and allied conditions. 13-th ed. Baltimore: Williams & Wilkins; 1996. 439-478.
  12. Nakamura M., Manser Т., Pearson G. et al. Effect of IFN-gamma on the immune response in vivo and in gene expression in vitro. Nature 1984; 307: 381-382.
  13. Dancis V., Frank G., Rathgen D. et al. Effect of GM-CSF, IL-2, IFN-gamma, TNF-alfa and IL-6 on the production of immunoreactive IL-1 and TNF-alfa by human monocytes. Clin. Exp. Immunol. 1991; 85: 143-147.
  14. Dayer J. M. Cytokines, soluble cytokine receptors and cytokine receptor antagonists. EULAR Bull. 1992; 21: 7-14.
  15. Duff G. W. Cytokines and acute phase proteins in rheumatoid arthritis. Scand. J. Rheumatol. 1994; 23 (suppl. 100): 9-19.
  16. Pike M. C. Structure and function of monocytes and macrophages. In: Koopman W. J., ed. Arthritis and allied conditions. 13-th ed. Baltimore: Williams & Wilkins; 1996. 339-354.
  17. Prud'homme G. J., Lawson B. R., Theophylopoulos A. N. Anticytokine gene therapy of autoimmune diseases. Expert Opin. Biol. Ther. 2001; 1: 359-373.
  18. Machold K. P., Smolen J. S. Interferon-gamma induced exacerbation of systemic lupus erythematosus. J. Rheumatol. 1990; 17: 831-832.
  19. Dolhain R. J., ter Haar N. Т., Hoefakker S. et al. Increased expression of interferon (IFN)-gamma together with IFN-gamma receptor in the rheumatoid synovial membrane compared with synovium of patients with osteoarthritis. Br. J. Rheumatol. 1996; 35 (1): 24-32.
  20. Steiner G. IL-1, IL-6, TNF-alfa and IFN-gamma: serum and synovial fluid concentration in rheumatoid arthritis. EULAR Cong. Rep. 1992; 1: 19-20.
  21. Лукина Г. В., Сигидин Я. А., Скуркович С. В. и др. Новые направления в антицитокиновой терапии ревматоидного артрита (первый опыт использования антиинтерферонов). Клин. ревматол. 1997; 3: 9-16.
  22. Лукина Г. В., Сигидин Я. А., Скуркович С. В. и др. Двойное слепое исследование сравнительной эффективности антител к интерферону у и фактору некроза опухоли α при ревматоидном артрите. Тер. арх. 2001; 5: 12-15.
  23. Arnett F. С., Edworthy S. М., Bloch D. A. et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthr. and Rheum. 1988; 31 (3): 315-324.
  24. Skurkovich S. V., Loukina G. V., Sigidin Y. A. et al. Successful first-time use of antibodies to interferon-gamma alone and combined with antibodies to tumor necrosis factor-alfa to treat rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, Behcet's syndrome). Inter. J. Immunother. 1998; 14 (1): 23-32.
  25. Felson D. Т., Anderson J. J., Boers M. et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. Arthr. and Rheum. 1993; 36 (6): 729-740.
  26. Elliot M. J., Maini R. N., Feldmann M. et al. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumour necrosis factor α. Arthr. and Rheum. 1993; 36 (12): 1681-1690.
  27. Maini R., Breedveld F., Kalden J. et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor α monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthr. and Rheum. 1998; 41 (9): 1552-1563.
  28. Sigidin Y. A., Loukina G. K., Skurkovich B. et al. Randomized, double-blind trial of anli-interferon-γ antibodies in rheumatoid arthritis. Scand. J. Rheumatol. 2001; 30 (4): 203-207.
  29. Skurkovich S. V., Boiko A., Beliaeva I. et al. Randomized study of antibodies to IFN-γ and TNF-α in secondary progressive multiple sclerosis. Multiple Scleros. 2001; 7: 277-284.
  30. Panitch H. S., Folus J. S., Johnson K. P. Recombinant Β-interferon inhibits γ-interferon production in multiple sclerosis. Ann. Neurol. 1987; 22: 139.
  31. Skurkovich S., Kasparov A., Narbut N. et al. Treatment of corneal transplant rejection in humans with anti-interferon-γ antibodies. Am. J. Ophthalmol. 2002; 133: 136-137.
  32. Skurkovich S., Korotky N., Sharova N. et al. Anti-interferon-γ to treat alopecia areata, psoriasis vulgaris, vitiligo, pemphigus vulgaris, and epidermolysis bullosa. In: The 5th Asia pacific congress of allergology and clinical immunology. Bologna: Monduzzi; 2002. 121-125.
  33. Ettefagh L., Nedorost S., Mirmirani P. Alopecia areata in a patient using infliximab. Arch. Dermatol. 2004; 140: 1012.
  34. Hommes D. W., Mikhajlova T. L., Stoinov S. et al. Fontolizumab, a humanised anti-interferon γ antibody, demonstrates safety and clinical activity in patients with moderate to severe Crohn's disease. Gut 2006; 56: 1131-1137.
  35. Crow M. K. Interferon-α: A new target for therapy in systemic lupus erythematosus? Arthr. and Rheum. 2003; 48 (9): 2396-2401.

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