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Erik Letko, Steven Yeh, Cynthia Grosskreutz, Uwe Pleyer, C. Stephen Foster, Mitchell Brigell; IV Secukinumab Is An Effective Treatment In Patients With Noninfectious Uveitis Requiring Steroid Sparing Immunosuppressive Therapy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5929.
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Secukinumab is a fully human monoclonal antibody that binds to IL-17A. In a proof of concept study 13/16 patients with active noninfectious uveitis were able to taper corticosteroids over 6 weeks with reduction of vitreous haze (VH) by at least one grade, following 1 or 2 intravenous (IV) infusions of Secukinumab 10 mg/kg (Sci Transl Med 2010;2:52RA72). Subsequent randomized controlled studies (RCTs) using subcutaneous (sc) Secukinumab at doses of 150 - 300 mg in patients with Behçet’s uveitis or quiescent noninfectious uveitis failed to show efficacy (Ophthalmol, in press). In this study we examined the efficacy of IV vs. sc Secukinumab in patients with active non-infectious intermediate, posterior, or pan-uveitis.
37 patients requiring steroid sparing immunomodulatory therapy, were randomized to receive either Secukinumab 300 mg sc every 2 wks, 10 mg/kg IV every 2 wks or 30 mg/kg IV every 4 wks. Patients were required to have a VH of ≥ 1+ treated with topical or oral corticosteroids. Corticosteroids were tapered over the course of the trial. Responders were patients whose VH improved by 2 grades or to grade 0 or trace at week 8. A patient was in remission if the vitreous and anterior chamber showed no sign of inflammation. Superiority was defined as a ≥ 50% probability of one treatment having 30% more responders or remissions. Similarity was defined as a ≥ 50% probability that the true difference between treatment response or remission rates was ± 20%.
The percent of responders to Secukinumab was similar between the two IV groups (62% 10 mg/kg; 73% 30 mg/kg) and both were superior to the 300 mg sc group (33%). A similar trend was seen for remissions with 27%, 37% and 17% of patients in remission at week 8 in the 30 mg/kg IV, 10 mg/kg IV, and 300 mg sc groups, respectively. The drug was well tolerated with no trend to increasing adverse events with increasing dose.
IV Secukinumab is an efficacious and safe steroid sparing treatment for patients with active non-infectious uveitis. The modest efficacy of 300 mg sc Secukinumab and its failure in prior uveitis RTCs could be explained by inadequate Cmax, since this dose has been shown to be sufficient to neutralize peripheral IL-17A. Our results suggest that high Cmax achieved by IV dosing is needed to have an effect on active non-infectious uveitis.
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