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 μg (n = 208), 440 μg (n = 208), or 880 μg (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-μg group was terminated after interim results found no significant difference in efficacy compared with the 440-μg 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 μg compared with 44 μg 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 letters in 80.1% and 80.2% of patients in the 440-μg and 44-μg groups, respectively. At month 5, corticosteroids were tapered successfully in 69.6% and 68.8% of patients in the 440-μg and 44-μg groups, and among these patients, VH of 0 or 0.5+ was achieved by 43.5% and 28.1% in the 440-μg and 44-μg 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 μg improved ocular inflammation, as measured by VH, compared with the 44-μg dose, with minimal impact on IOP, while preserving BCVA.