International Ophthalmology

, Volume 26, Issue 3, pp 83–92 | Cite as

Long-term safety and efficacy of infliximab therapy in refractory uveitis due to Behçet’s disease

  • Ahmed M. Abu El-Asrar
  • Emad B. Abboud
  • Hassan Aldibhi
  • Abdulrahman Al-Arfaj
Original Paper


Purpose To evaluate the long-term safety and efficacy of infliximab therapy for refractory uveitis associated with Behçet’s disease (BD).

Methods We prospectively enrolled six patients who failed to respond to conventional immunosuppressive treatment. Infliximab infusions (5 mg/kg) were administered at weeks 0, 2, 6, and then every 8 weeks. The outcome variables were visual acuity, control of inflammation, reduction of macular edema, tapering of immunosuppressive therapy, and adverse effects.

Results The follow-up period ranged from 16 to 36 months (mean ± SD, 23 ± 7.4 months). The number of infliximab infusions ranged from 10 to 23 (14 ± 4.6). By the 2-month follow-up, all patients had achieved remission, the cystoid macular edema had resolved, and visual acuity had improved dramatically. Throughout the follow-up period, three patients remained attack-free. One patient had one relapse, and another patient had two relapses before the scheduled infusions; all three relapses resolved rapidly after the subsequent infusion. One patient developed five relapses, and infusions at 6-week intervals were necessary to achieve sustained remission. At the end of the follow-up period, visual acuity improved in five patients. Concomitant immunosuppressive therapy was substantially reduced. Antinuclear antibodies developed in two patients who received 17 and 23 infusions. No major adverse effects requiring withdrawal of infliximab were observed.

Conclusion Infliximab is efficient and safe for long-term treatment of refractory uveitis associated with BD. Repeated infusions are required to maintain long-term remission.


Anti-tumor necrosis factor-α antibody Behçet’s disease Uveitis 



The authors thank Ms. Connie B. Unisa-Marfil for secretarial work. This work was partially supported by the College of Medicine Research Center, King Saud University, Riyadh, Saudi Arabia.


  1. 1.
    International Study Group for Behçet’s Disease (1990) Criteria for diagnosis of Behçet’s disease. Lancet 335:1078–1080Google Scholar
  2. 2.
    Sakane T, Takeno M (2000) New approaches to Behçet’s disease. Exp Opin Invest Drugs 9:1993–2005CrossRefGoogle Scholar
  3. 3.
    Tugal-Tutkun I, Onal S, Altan-Yaycioglu R, Huseyin Altunbas H, Urgancioglu M (2004) Uveitis in Behçet’s disease: an analysis of 880 patients. Am J Ophthalmol 138:373–380PubMedCrossRefGoogle Scholar
  4. 4.
    Frassanito MA, Dammacco R, Cafforio P, Dammacco F (1999) Th1 polarization of the immune response in Behçet’s disease: a putative pathogenetic role of interleukin-12. Arthritis Rheum 42:1967–1974PubMedCrossRefGoogle Scholar
  5. 5.
    Abu El-Asrar AM, Struyf S, Descamps FJ, Al-Obeidan SA, Proost P, Van Damme J et al. (2004) Chemokines and gelatinases in the aqueous humor of patients with active uveitis. Am J Ophthalmol 138:401–411PubMedCrossRefGoogle Scholar
  6. 6.
    Mage JL, Dilsen N, Sanguedolce V, Gul A, Bangrand P, Roux H et al. (1993) Overproduction of monocyte derived tumor necrosis factor alpha, interleukin (IL) 6, IL-8 and increased neutrophil superoxide generation in Behçet’s disease. a comparative study with familial Mediterranean fever and healthy subjects. J Rheumatol 20:1544–1549Google Scholar
  7. 7.
    Misumi M, Hagiwara E, Takeno M, Takeda Y, Inoue Y, Tsuji T et al. (2003) Cytokine production profile in patients with Behçet’s disease treated with infliximab. Cytokine 24:210–218PubMedCrossRefGoogle Scholar
  8. 8.
    Turan B, Gallati H, Erdi H, Gurler A, Michel BA, Villiger PM (1997) Systemic levels of the T cell regulatory cytokines IL-10 and IL-12 in Behçet’s disease; soluble TNFR-75 as a biological marker of disease activity. J Rheumatol 24:128–132PubMedGoogle Scholar
  9. 9.
    Evereklioglu C, Er H, Turkoz Y, Cekmen M (2002) Serum levels of TNF-alpha, sIL-2R, IL-6, and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behçet’s disease. Mediat Inflamm 11:87–93CrossRefGoogle Scholar
  10. 10.
    Bardak Y, Aridogan BC (2004) The demonstration of serum interleukin 6–8, tumor necrosis factor-alpha, complement, and immunoglobulin levels in Behçet’s disease with ocular involvement. Ocul Immunol Inflamm 12:53–58PubMedCrossRefGoogle Scholar
  11. 11.
    Santos Lacomba M, Marcos Martin C, Gallardo Galera JM, Gomez Vidal MA, Collantes Estevez E, Ramirez Chamond R et al. (2001) Aqueous humor and serum tumor necrosis factor-alpha in clinical uveitis. Ophthalmic Res 33:251–255PubMedCrossRefGoogle Scholar
  12. 12.
    Greiner K, Murphy CC, Willermain F, Duncan L, Plskova J, Hale G et al (2004) Anti-TNF ( therapy modulates the phenotype of peripheral blood CD4+ T cells in patients with posterior segment intraocular inflammation. Invest Ophth Vis Sci 45:170–176CrossRefGoogle Scholar
  13. 13.
    Sfikakis PP, Kaklamanis PH, Elezoglou A, Katsilambros N (2004) Infliximab for recurrent sight-threatening ocular inflammation in Adamantiades-Behçet’s disease. Ann Intern Med 140:404–406PubMedGoogle Scholar
  14. 14.
    Joseph A, Raj D, Dua HS, Powell PT, Lanyon PC, Powell RJ (2003) Infliximab in the treatment of refractory posterior uveitis. Ophthalmology 110:1449–1453PubMedCrossRefGoogle Scholar
  15. 15.
    Tugal-Tutkun I, Mudun A, Urgancioglu M, Kamali S, Kasapoglu E, Inanc M et al. (2005) Efficacy of infliximab in the treatment of uveitis that is resistant to treatment with the combination of azathioprine, cyclosporine, and corticosteroids in Behçet’s disease. Arthritis Rheum 52:2478–2484PubMedCrossRefGoogle Scholar
  16. 16.
    Ohno S, Makamura S, Hori S, Shimakawa M, Kawashima H, Mochizuki M et al. (2004) Efficacy, safety, and pharmacokinetics of multiple administration of infliximab in Behçet’s disease with refractory uveoretinitis. J Rheumatol 31:1362–1368PubMedGoogle Scholar
  17. 17.
    Sfikakis PP (2002) Behçet’s disease: a new target for anti-tumor necrosis factor treatment. Ann Rheum Dis 61:51–53Google Scholar
  18. 18.
    Lindstedt EW, Baarsma GS, Kuijpers RWAM, van Hagen PM (2005) Anti-TNF-α therapy for sight threatening uveitis. Br J Ophthalmol 89:533–536PubMedCrossRefGoogle Scholar
  19. 19.
    Lantbier N, Parc C, Scavennec R, Dbôte R, Brézin AP, Guillevin L (2005) Infliximab in the treatment of posterior uveitis in Behçet’s disease: long term follow-up in four patients. Press Med 34:916–918Google Scholar
  20. 20.
    Wechsler B, Sable-Fourtassou R, Bodaghi B, Huong DL, Cassoux N, Badelon I et al. (2004) Infliximab in refractory uveitis due to Behçet’s disease. Clin Exp Rheumatol 22[Suppl 4]:S14–S16PubMedGoogle Scholar
  21. 21.
    Benitez-del-Castillo JM, Martinez-de-la-Casa JM, Pato-Cour E, Mendez-Fernandez R, Lopez-Abad C, Matilla M, Garcia-Sanchez J (2005) Long-term treatment of refractory posterior uveitis with anti-TNF alpha (infliximab). Eye 19:831–833CrossRefGoogle Scholar
  22. 22.
    Suhler EB, Smith JR, Werheim MS, Lauer AK, Kurz DE, Richard TD et al. (2005) A prospective trial of infliximab therapy for refractory uveitis: preliminary safety and efficacy outcomes. Arch Ophthalmol 123:903–912PubMedCrossRefGoogle Scholar
  23. 23.
    Forrester JV, Ben Ezra D, Nussenblatt RB, Tabbara KF, Timonen P (1994) Grading of intermediate, posterior uveitis. In: Tabbara KF, Nussenblatt RB (eds) Posterior uveitis: diagnosis and management. Butterworth-Heinemann, Boston, pp 5–18Google Scholar
  24. 24.
    Markomichelakis NN, Theodossiadis PG, Pantelia E, Papaefthimiou S, Theodossiadis GP, Sfikakis PP (2004) Infliximab for chronic cystoid macular edema associated with uveitis. Am J Ophthalmol 138:648–650PubMedCrossRefGoogle Scholar
  25. 25.
    Louis M, Rauch J, Armstrong M, Fitzcharles MA (2003) Induction of autoantibodies during prolonged treatment with infliximab. J Rheumatol 30:2557–2562PubMedGoogle Scholar
  26. 26.
    Allanore Y, Sellam J, Batteux F, Job Deslandre C, Weill B, Kahan A (2004) Induction of autoantibodies in refractory rheumatoid arthritis treated by infliximab. Clin Exp Rheumatol 22:756–758PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Ahmed M. Abu El-Asrar
    • 1
    • 2
  • Emad B. Abboud
    • 3
  • Hassan Aldibhi
    • 3
  • Abdulrahman Al-Arfaj
    • 4
  1. 1.Department of Ophthalmology, College of MedicineKing Saud UniversityRiyadhSaudi Arabia
  2. 2.Department of OphthalmologyKing Abdulaziz University HospitalRiyadhSaudi Arabia
  3. 3.King Khaled Eye Specialist HospitalRiyadhSaudi Arabia
  4. 4.Department of Medicine (Rheumatology Division), College of MedicineKing Saud UniversityRiyadhSaudi Arabia

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