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R. R. Buggage, H. B. Richards, M.-A. Valentin, I. Koroleva, T. B. Dryja; The Study of IL-17A Expression as a Biomarker for Patients With Active Noninfectious Uveitis Treated With AIN457. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3779.
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Higher IL-17 expression has been detected in patients with active uveitis and Behçet’s disease compared to patients with inactive disease and healthy controls. AIN457 offers a novel therapeutic strategy for noninfectious uveitis including Behçet’s uveitis. The effect of AIN457 on IL-17A expression and the correlation between baseline IL-17A and treatment response were evaluated in an open-label study.
16 patients with active noninfectious uveitis of various etiologies were treated with 2 intravenous doses of AIN457 at day 0 and 21 and followed through week 8. Serum IL-17A was measured on day 0 using a highly sensitive immunoassay coupled to single photon detection and mRNA levels were measured on day 0, weeks 1,2,3,4 and 8 by RT-PCR.
Treatment with AIN457 reduced intraocular inflammation, improved visual acuity or allowed for reduction of concomitant corticosteroids in 11/16 patients. While the mean baseline IL-17A level in patients with active uveitis was higher than in healthy subjects (0.47 vs 0.26 pg/ml; p=0.05), the difference was mainly due to a single outlier. After excluding this patient, there was no significant difference in baseline IL-17A levels comparing study patients and controls. Poor correlation existed between baseline serum IL-17A protein levels and IL-17A mRNA expression in whole blood. No obvious relationship existed between IL-17A mRNA levels in whole blood and response to treatment.
Although baseline serum levels and expression of IL-17A were not elevated in this active uveitis study population, the clinical findings support the role of IL-17A in the pathogenesis of human uveitis and suggest that IL-17A inhibition with AIN457 may be efficacious for the treatment of noninfectious uveitis. Moreover these results indicate that ocular elevation of IL-17A may be locally confined and not measurable in the circulation. Additional studies are needed to understand the value of measuring circulating IL-17A in patients with noninfectious uveitis as a potential biomarker predictive of response to therapy with AIN457.
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