One-Year Outcomes of the SAVE Study: Sirolimus as a Therapeutic Approach for UVEitis.

Abstract

To determine the efficacy and safety of repeated intravitreal and subconjunctival administrations of sirolimus in patients with noninfectious uveitis at 1 year in the Sirolimus as a Therapeutic Approach UVEitis (SAVE) Study. Open-label, prospective, and randomized interventional clinical trial in which 30 patients with noninfectious intermediate, posterior, or panuveitis were randomized 1:1 to receive sirolimus 352-μg intravitreal or 1320-μg subconjunctival. Sirolimus was administered at days 0, 60, and 120. At month 6, all subjects were allowed to receive sirolimus at intervals greater than or equal to 2 months and until month 12. Changes in vitreous haze (VH), visual acuity (VA), and retinal thickness at month 12 were compared with baseline. Of patients with active uveitis at baseline (n = 20), 70% showed greater than or equal to 2 steps reduction of VH at month 12 (P < 0.05), 88% (n = 7) of patients with inactive uveitis at baseline showed either no change or reduction of VH to no haze, 36% (n = 10) of all patients (n = 28) gained greater than or equal to one line of VA, 21% (n = 6) lost greater than or equal to 1 line, and 43% (n = 12) showed no change. At the end of 1 year, no statistical differences in efficacy were found between intravitreal and subconjunctival groups. No serious adverse events were determined to be secondary to sirolimus. Repeated subconjunctival/intravitreal injections of sirolimus appear to be tolerated by patients with noninfectious uveitis over 12 months. Results from the index study suggest that sirolimus may provide benefits to patients with uveitis. Both intravitreal and subconjunctival routes demonstrate similar bioactivity/efficacy. The intravitreal route, however, was better tolerated. The SAVE Study illustrates for the first time the application of local formulations of sirolimus in non-infectious intermediate, posterior, and pan-uveitis. Subconjunctival/Intravitreal sirolimus may help to control inflammation while offering better tolerability/safety profiles than systemic therapies, including immunosuppressants and corticosteroids.