Results from the SAKURA program: central retinal thickness changes with intravitreal sirolimus in subjects with non‐infectious uveitis of the posterior segment and macular edema at baseline

Abstract

PurposeTo evaluate the effects of intravitreal (IVT) sirolimus on central retinal thickness (CRT) in subjects with non‐infectious uveitis of the posterior segment (NIU‐PS) with macular edema (ME) in the SAKURA program.MethodsThe SAKURA program consisted of two Phase 3 international, randomized, double‐masked studies evaluating the efficacy and safety of every‐other‐month IVT sirolimus in subjects with active NIU‐PS. Inclusion criteria included vitreous haze (VH) ≥1.5 + . Subjects from both studies comprised the integrated intent‐to‐treat population evaluating IVT sirolimus 440 μg (n = 208) vs 44 μg (active control; n = 208). Primary endpoint: VH=0 at Month 5 (M5). Change in CRT at M5 was assessed in subjects with baseline ME (CRT ≥300 μm).ResultsIn the integrated analysis, 21.2% vs 13.5% of subjects in the 440‐ vs 44‐μg groups achieved VH=0 at M5 (p = 0.038). 68 (32.7%) subjects in the 440‐μg group and 65 (31.3%) in the 44‐μg group had ME at baseline (mean CRT 501.65 μm and 507.89 μm, respectively). Of these, 19.1% and 12.3% in the 440‐ and 44‐μg groups, respectively, achieved VH=0 at M5 (p = 0.282). M5 CRT data were available for 47 and 51 subjects not rescued before M5 in the 440‐ and 44‐μg groups, respectively, with corresponding median % CRT changes from baseline of ‐20.6% and ‐15.5%. Median % CRT changes at M5 were greatest in subjects in the 440‐μg group without epiretinal membrane: ‐55.6% vs ‐2.3% in the 440‐ vs 44‐μg groups (p = 0.029). Serious ocular adverse events were reported in 14.9% and 14.3% of subjects with baseline ME in the 440‐ and 44‐μg groups, respectively.ConclusionsAn integrated analysis of the SAKURA program demonstrated that the mTOR inhibitor IVT sirolimus 440 μg can result in statistically significant improvements in VH in subjects with active NIU‐PS and can improve CRT in subjects with ME.