Efficacy and Safety of Intravitreal Sirolimus for Noninfectious Uveitis of the Posterior Segment Results from the Sirolimus Study Assessing Double-Masked Uveitis Treatment (SAKURA) Program

Purpose: To evaluate the efficacy and safety of intravitreal sirolimus in the management of noninfectious uveitis of the posterior segment (NIU-PS). Design: Combined analysis of 2 phase 3, randomized, double-masked, multinational, 6-month studies. Participants: Adults with active NIU-PS (intermediate uveitis, posterior uveitis, or panuveitis; defined as vitreous haze [VH] >= 1.5+ on modified Standardization of Uveitis Nomenclature scale). Methods: Patients were randomized 1:1:1 to receive intravitreal sirolimus 44 mu g (n = 208), 440 mu g (n = 208), or 880 mu g (n = 177) on days 1, 60, and 120. Patients discontinued medications for NIU-PS except for systemic corticosteroids, which were tapered according to protocol. Enrollment in the 880-mu g group was terminated after interim results found no significant difference in efficacy compared with the 440-mu g dose. Main Outcome Measures: The primary efficacy end point was the percentage of patients with VH of 0 at month 5 in the study eye without the use of rescue therapy. Secondary efficacy end points included VH of 0 or 0.5+, corticosteroid-tapering success, and changes in best-corrected visual acuity (BCVA). Safety measures included ocular and nonocular adverse events. Results: A total of 592 patients were randomized. Significantly higher proportions of patients treated with 440 mu g compared with 44 mu g intravitreal sirolimus achieved VH of 0 (21.2% vs. 13.5%; P = 0.038) and VH of 0 or 0.5+ (50.0% vs. 40.4%; P = 0.049) at month 5. Best-corrected visual acuity was stable (absolute change <5 ETDRS letters) or improved >5 letters in 80.1% and 80.2% of patients in the 440-mu g and 44-mu g groups, respectively. At month 5, corticosteroids were tapered successfully in 69.6% and 68.8% of patients in the 440-mu g and 44-mu g groups, and among these patients, VH of 0 or 0.5+ was achieved by 43.5% and 28.1% in the 440-mu g and 44-mu g groups. Both doses were generally well tolerated. Mean changes from baseline intraocular pressure (IOP) in the study eye at each analysis visit were minimal in all treatment groups. Conclusions: Intravitreal sirolimus 440 mu g improved ocular inflammation, as measured by VH, compared with the 44-mu g dose, with minimal impact on IOP, while preserving BCVA. (C) 2020 by the American Academy of Ophthalmology.