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Efficacy of recombinant human interferon-alfa2a on ocular and extra-ocular manifestations of Behçet's disease and influence on cells of the immune system: results of an open four center trial
Arthritis Res Ther volume 5, Article number: 5 (2003)
Behçet's disease (BD) is a multisystem vasculitis of unknown origin. Standard treatment comprises systemic immunosuppressive agents. In a study primarily designed for refractory ocular disease we additionally evaluated the efficacy of recombinant human interferon-alpha2a (rhIFN-alpha2a) for the extraocular manifestations.
Fifty patients were included in the study. rhIFN-alpha2a was applied at a dose of 6 million units subcutaneously daily. Dose reduction was performed according to a decision tree until discontinuation. Disease activity was evaluated by the Behçet's disease activity scoring system and the uveitis scoring system. In parallel, peripheral blood mononuclear cells (PBMC) from 14 patients and 10 healthy controls were isolated, stained with four different fluorescent dyes and measured with a fluorescence activated cell sorter (FACS). Statistical analysis was performed by ANCOVA and Welsh test.
Response rate of the ocular manifestations was 92%. Visual acuity rose significantly from 0.56 to 0.84 at week 24 (P < 0.0001). Posterior uveitis score of the affected eyes fell by 46% in 1 week (P < 0.001). Mean BD activity score fell in a dose-dependent fashion by 1.2 points in the first week (P < 0.0001) and from 5.8 to 3.3 at week 24. After a mean observation period of 36.4 months, 17 patients are off treatment and disease free for 29.5 months (mean). In the other patients maintenance dosage is 3 million units 3 times weekly. Whereas extraocular manifestations such as genital ulcerations, arthritis and skin lesions remitted under IFN, this was the case only for 36% of oral aphthous ulcers. The lymphocyte subpopulations showed a significant increase of γδ positive T cells and NK cells in the patients before treatment when compared with healthy controls. Under IFN treatment, they decreased significantly and almost reached the level of the control group. Additionally, monocytes and B cells increased.
rhIFN-alpha2a is effective in ocular BD, resulting in significant improvement in vision and complete remission of ocular vasculitis in the majority of the patients. It is also effective for the extraocular manifestations of the disease, although less so for oral aphthous ulcers. A participation of γδ positive T cells and NK cells in the pathogenesis of BD is implicated; their decrease may explain the mechanism by which IFN-alpha exerts its therapeutic effects, whereas the increase of monocytes and B cells may be responsible for side effects of IFN such as flu-like syndrome and autoimmune phenomena.
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Kötter, I., Treusch, M., Vonthein, R. et al. Efficacy of recombinant human interferon-alfa2a on ocular and extra-ocular manifestations of Behçet's disease and influence on cells of the immune system: results of an open four center trial. Arthritis Res Ther 5, 5 (2003) doi:10.1186/ar980
- Fluorescence Activate Cell Sorter
- Genital Ulceration
- Ocular Manifestation