Advertisement

Rheumatology International

, Volume 31, Issue 1, pp 33–37 | Cite as

One year study of efficacy and safety of infliximab in the treatment of patients with ocular and neurological Behçet’s disease refractory to standard immunosuppressive drugs

  • AnnaRita Giardina
  • Angelo Ferrante
  • Francesco Ciccia
  • Maria Vadalà
  • Ennio Giardina
  • Giovanni Triolo
Original Article

Abstract

The aim of the study was to assess the long-term efficacy and safety of Infliximab therapy in the treatment of patients with Behçet’s disease refractory to standard immunosuppressive agents. Twenty-one patients that did not respond to corticosteroids and to at least one immunosuppressant (cyclosporin, methotrexate, azathioprine, cyclophosphamide) for the presence of ocular and/or CNS involvement were enrolled. Eighteen patients completed the study up to 54 weeks. Stable doses of prednisone (<10 mg/day) were permitted, immunosuppressants were discontinued at least 4 weeks prior baseline visit. The patients received three infusions of 5 mg/kg Infliximab (at weeks 0, 2 and 6) and then infusions of 5 mg/kg Infliximab every 8 weeks. At each visit data on clinical symptoms, response to therapy and adverse events were collected. The primary outcome of interest was to assess the clinical efficacy (total or partial recovery) of infliximab. Secondary end points were to evaluate quality of life and to monitor the safety of the drug. Eighteen patients achieved a total remission. Two patients achieved a partial remission and relapsed after 3 months from discontinuation of therapy. Infliximab was well tolerated throughout the study. A case of non-Hodgkin lymphoma was observed within 6 months. Minor side effects were headache, dizziness, tachycardia that regressed spontaneously and did not entail interruption. Anti-nuclear antibodies were not detected during the period of observation.

Keywords

Behçet’s disease TNF alfa Infliximab 

References

  1. 1.
    Kaklamani VG, Variopoulos G, Kaklamanis PG (1998) Behçet’s disease. Semin Arthritis Rheum 27:197–217CrossRefPubMedGoogle Scholar
  2. 2.
    Nussenblatt RB (1997) Uveitis in Behçet’s disease. Int Rev Immunol 14:67–79PubMedGoogle Scholar
  3. 3.
    Nakae K, Masaki F, Hashimoto T, Inaba G, Mochizuki M, Sakane T (1993) Recent epidemiological features of Behçet’s disease in Japan. In: Wechsler B, Godeau P (eds) Behçet’s disease. Excerpta Medica, Amsterdam, pp 145–151Google Scholar
  4. 4.
    Zouboulis CC, Kötter I, Djawari D et al (1997) Epidemiological features of Adamantiades-Behçet’s disease in Germany and in Europe. Yonsei Med J 38:411–422PubMedGoogle Scholar
  5. 5.
    Dilsen N, Konice M, Aral O, Öcal L, Inanc M, Gill A (1993) Risk factors for vital organ involvement in Behçet’s disease. In: Wechsler B, Godeau P (eds) Behçet’s disease. Excerpta Medica, Amsterdam, pp 165–169Google Scholar
  6. 6.
    Mamo JG (1970) The rate of visual loss in Behçet’s disease. Arch Ophthalmol 84:451–452PubMedGoogle Scholar
  7. 7.
    Pipitone N, Olivieri I, Cantini F, Triolo G, Salvarani C (2006) New approaches in the treatment of Adamantiades-Behçet’s diseases. Curr Opin Rheumatol 18:3–9CrossRefPubMedGoogle Scholar
  8. 8.
    Sayinalp N, Ozcebe OI, Ozdenir O, Haznedaroglu IC, Dundar S, Kirazli S (1996) Cytokines in Behçet’s disease. J Rheumatol 23:321–322PubMedGoogle Scholar
  9. 9.
    Frassanito MA, Dammacco R, Cafforio P, Dammacco F (1999) Th1 polarization of the immune response in Behçet’s disease: a putative role of interleukin-12. Arthritis Rheum 42:1967–1974CrossRefPubMedGoogle Scholar
  10. 10.
    Triolo G, Accardo-Palumbo A, Dieli F, Ciccia F, Ferrante A, Giardina E, Licata G (2002) Humoral and cell mediated immune response to cow’s milk proteins in Behcet’s disease. Ann Rheum Dis 61:459–462CrossRefPubMedGoogle Scholar
  11. 11.
    Caspi RR (2002) Th1 and Th2 responses in pathogenesis and regulation of experimental autoimmune uveoretinitis. Int Rev Immunol 21:197–208CrossRefPubMedGoogle Scholar
  12. 12.
    Triolo G, Accardo-Palumbo A, Dieli F, Ciccia F, Ferrante A, Giardina E, Sano CD, Licata G (2003) Vgamma9/Vdelta2 T lymphocytes in Italian patients with Behcet’s disease: evidence for expansion, and tumour necrosis factor receptor II and interleukin-12 receptor beta1 expression in active disease. Arthritis Res Ther 5:R262–R268CrossRefPubMedGoogle Scholar
  13. 13.
    Todaro M, Zerilli M, Triolo G, Iovino F, Patti M et al (2005) NFkB protects Behçet’s disease T cells against CD95 induced apoptosis upregulating anti apoptotic proteins. Arthritis Rheum 52:2179–2191CrossRefPubMedGoogle Scholar
  14. 14.
    Sfikakis PP, Theodossiadis PG, Katsiari CG, Kaklamanis P, Markomichelakis NN (2001) Effect of infliximab on sight-threatening panuveitis in Behcet’s disease. Lancet 28;358(9278):295–296CrossRefGoogle Scholar
  15. 15.
    Triolo G, Vadala M, Accardo-Palumbo A, Ferrante A, Ciccia F, Giardina E, Citarrella P, Lodato G, Licata G (2002) Anti-tumour necrosis factor monoclonal antibody treatment for ocular Behcet’s disease. Ann Rheum Dis 61:560–561CrossRefPubMedGoogle Scholar
  16. 16.
    Al-Rayes H, Al-Swallen R, Al-Balawi M et al (2008) Safety and efficacy of infliximab therapy in active Behçet’s uveitis: an open-label study. Rheumatol Int 29:53–57CrossRefPubMedGoogle Scholar
  17. 17.
    Licata G, Pinto A, Tuttolomondo A, Banco A, Ciccia F, Ferrante A, Triolo G (2003) Anti-tumor necrosis factor alpha monoclonal antibody therapy for recalcitrant cerebral vasculitis in a patient with Behçet’s syndrome. Ann Rheum Dis 62:280–281CrossRefPubMedGoogle Scholar
  18. 18.
    Pipitone N, Olivieri I, Padula A et al (2009) Infliximab for the treatment of neuro-Beheçet’s disease: a case series and review of the literature. Arthritis Rheum 59:285–290CrossRefGoogle Scholar
  19. 19.
    Goossens PH, Verburg RJ, Bredveld FC (2001) Remission of Behçet’s syndrome with tumour necrosis factor α blocking therapy. Ann Rheum Dis 60:637CrossRefPubMedGoogle Scholar
  20. 20.
    Hassard PV, Binder SW, Nelson V, Vasiliauskas EA (2001) Anti-tumor necrosis factor monoclonal antibody therapy for gastrointestinal Behcet’s disease: a case report. Gastroenterology 120:995–999CrossRefPubMedGoogle Scholar
  21. 21.
    Travis SP, Czajkowski M, McGovern DP, Watson RG, Bell AL (2001) Treatment of intestinal Behcet’s syndrome with chimeric tumour necrosis factor alpha antibody. Gut 49:725–728CrossRefPubMedGoogle Scholar
  22. 22.
    International Study Group for Behçet’s Disease (1990) Criteria for diagnosis of Behçet’s disease. Lancet 335:995–999Google Scholar
  23. 23.
    Bahcta BB, Brennan P, James TE, Chamberlain A, Noble BA, Silman AJ (1999) Behçet’s disease: evaluation of a new instrument to measure clinical activity. Rheumatology 38:728–735CrossRefGoogle Scholar
  24. 24.
    Lawton G, Bahcta BB, Chamberlain AA, Tennant A (2004) Behçet’s disease activity index. Rheumatology 43:73–78CrossRefPubMedGoogle Scholar
  25. 25.
    Jabs DA, Nussenblatt RB, Rosenbaum JT (2005) Standardization of uveitis nomenclature (SUN) working group, Standardization of uveitis nomenclature for reporting clinical data Results of the first international workshop. Am J Ophtalmol 140:509–516CrossRefGoogle Scholar
  26. 26.
    Hatemi G, Silman A, Bang D, Bodaghi B et al (2008) EULAR recommendations for the management of Behçet’s disease: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum DisGoogle Scholar
  27. 27.
    Katsura Y, Suzukawa K, Kojima H, Yoshida C, Shimizu S, Mukai H, Hasegawa Y, Imagawa S, Mori N, Nagasawa T (2003) Cytotoxic T-cell lymphoma arising in Behcet disease. Int J Hematol 77:282–285CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • AnnaRita Giardina
    • 1
  • Angelo Ferrante
    • 1
  • Francesco Ciccia
    • 1
  • Maria Vadalà
    • 2
  • Ennio Giardina
    • 1
  • Giovanni Triolo
    • 1
    • 3
  1. 1.Chair and Division of RheumatologyUniversity of PalermoPalermoItaly
  2. 2.Chair and Division of OphthalmologyUniversity of PalermoPalermoItaly
  3. 3.Unità Operativa e Cattedra di ReumatologiaPalermoItaly

Personalised recommendations