Abstract
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.
Similar content being viewed by others
References
International Study Group for Behçet’s Disease (1990) Criteria for diagnosis of Behçet’s disease. Lancet 335:1078–1080
Sakane T, Takeno M (2000) New approaches to Behçet’s disease. Exp Opin Invest Drugs 9:1993–2005
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 138:373–380
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 42:1967–1974
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 138:401–411
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 20:1544–1549
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 24:210–218
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 24:128–132
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 11:87–93
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 12:53–58
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 33:251–255
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 45:170–176
Sfikakis PP, Kaklamanis PH, Elezoglou A, Katsilambros N (2004) Infliximab for recurrent sight-threatening ocular inflammation in Adamantiades-Behçet’s disease. Ann Intern Med 140:404–406
Joseph A, Raj D, Dua HS, Powell PT, Lanyon PC, Powell RJ (2003) Infliximab in the treatment of refractory posterior uveitis. Ophthalmology 110:1449–1453
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 52:2478–2484
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 31:1362–1368
Sfikakis PP (2002) Behçet’s disease: a new target for anti-tumor necrosis factor treatment. Ann Rheum Dis 61:51–53
Lindstedt EW, Baarsma GS, Kuijpers RWAM, van Hagen PM (2005) Anti-TNF-α therapy for sight threatening uveitis. Br J Ophthalmol 89:533–536
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 34:916–918
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–S16
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 19:831–833
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 123:903–912
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 5–18
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 138:648–650
Louis M, Rauch J, Armstrong M, Fitzcharles MA (2003) Induction of autoantibodies during prolonged treatment with infliximab. J Rheumatol 30:2557–2562
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 22:756–758
Acknowledgements
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Abu El-Asrar, A.M., Abboud, E.B., Aldibhi, H. et al. Long-term safety and efficacy of infliximab therapy in refractory uveitis due to Behçet’s disease. Int Ophthalmol 26, 83–92 (2005). https://doi.org/10.1007/s10792-006-9006-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10792-006-9006-9