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Quan Dong Nguyen, Mohamed Ibrahim, Anthony Watters, Yasir Sepah, Millena Bittencourt, Jithin Yohannan, Joel Naor, Naveed Shams, Diana Do; 12-Month Results of the SAVE Study - Sirolimus as Therapeutic Approach to UVEitis: A Randomized Study to Assess the Safety and Bioactivity of Intravitreal and Subconjunctival Injections of Sirolimus in Patients with Non-infectious Uveitis. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5931.
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Purpose: To present the one-year safety and bioactivity outcomes of sirolimus as an immunomodulatory therapeutic (IMT) agent, delivered subconjunctivally (SCJ) or intravitreally (IVT), in patients with non-infectious posterior, intermediate, or panuveitis.
Methods: 30 subjects were stratified at baseline (BL) into 3 categories: (1) active disease receiving no treatment; (2) active disease receiving prednisone ≥10 mg/day and/or at least one other IMT; (3) inactive disease receiving prednisone <10 mg/day and/or at least one other IMT. Patients in each category were randomized into SCJ or IVT arm (1:1). Study eyes received SCJ (1320 μg) or IVT (352 μg) injections at days 0, 60, and 120, with primary endpoint at day 180. Study subjects may be followed and treated until M12. Beyond safety, study parameters include change in visual acuity (VA), vitreous cells/haze, and reduction in dosage of systemic corticosteroid (CS) compared to BL.
Analyses at the 12-month endpoint were performed using data from 28 subjects; two subjects discontinued before M6. Both SCJ and IVT sirolimus injections were well tolerated. None of the adverse events (AE) were deemed to be related to sirolimus. At M12, VA improved ≥ 5 letters in 21% and 50%, ITV and SCJ respectively and stabilized in 43% of all patients. Vitreous haze improved in 70% of patients with active uveitis (SCJ=71%; IVT=71%). 20 patients were on systemic CS therapy at BL; all had their doses of CS reduced at M12. The mean dose among subjects who were on CS decreased from 20.5 mg/day at BL to 3.5 mg/day at M12.
Locally administered (subconjunctival or intravitreal) sirolimus appears safe in patients with noninfectious uveitis. Sirolimus has exerted its bioactivity in reducing vitreous haze and cells, improving VA, and in decreasing need for systemic CS over a 12-month period. Larger controlled trials are indicated to confirm the role of locally-delivered sirolimus and to determine its appropriate dosage and frequency of administration.
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