In the SAKURA program, 46 patients in the sirolimus 440-mcg group and 32 active control (sirolimus 44 mcg) patients were receiving an oral prednisone-equivalent dose >5 mg at study entry and were included in an Intent-to-Taper corticosteroid population. ![]() Analyses of the proportion of patients achieving a vitreous haze score of 0 by month 5 showed statistically significant differences favoring sirolimus 440 mcg over the 44-mcg dose in SAKURA 1, 2, and the pooled populations. Similarly, a key secondary endpoint analysis that considered the proportion of patients achieving a vitreous haze score of 0 or 0.5+ at month 5 showed a statistically significant difference favoring sirolimus 440 mcg over sirolimus 44 mcg in SAKURA 1 (52.6% verus 35.0% p = 0.0008), no significant difference comparing sirolimus 440 mcg and 44 mcg in SAKURA 2 due to a higher response rate in the active control group (47.3% versus 46.8% p = 0.952), but a statistically significant benefit of sirolimus 440 mcg in the integrated analysis (50.0% versus 40.4% p = 0.049).Ī post hoc efficacy analysis focused on the population of patients with multiple measures of inflammation at baseline as defined by a vitreous haze score ≥1.5+ and at least one of the following characteristics: BCVA ≤75 ETDRS letters, requirement for systemic corticosteroids, or presence of macular edema.Ībout 80% of patients in both the sirolimus 44- and 440-mcg groups met these criteria. However, integrated analysis of the SAKURA 1 and 2 data demonstrated statistically significant superiority of sirolimus 440 mcg to the 44-mcg dose. ![]() There was a 17.6% response rate in the sirolimus 44-mcg group and the difference between treatment groups was not statistically significant (p = 0.783). Consistent with the outcome in SAKURA 1, 19.1% of patients treated with sirolimus 440 mcg achieved a vitreous haze score of 0 at month 5. The protocol for SAKURA 2 was amended to eliminate further evaluation of the 880-mcg dose. The primary efficacy analysis-which determined the proportion of patients with a vitreous haze score of 0 at month 5-showed superiority of the 440-mcg dose compared with both the 44- and 880-mcg doses. In SAKURA 1, 347 patients were randomly assigned to receive either intravitreal sirolimus 440 mcg, 880 mcg, or 44 mcg once every 2 months. Topical corticosteroids and nonsteroidal immunosuppressive agents had to be stopped prior to enrollment, whereas existing systemic corticosteroid therapy >5 mg/day prednisone-equivalent was to be rapidly tapered after study entry. ![]() Inclusion/exclusion criteria required patients have a vitreous haze score ≥1.5+, BCVA ≥19 ETDRS letters (≥20/400) in the study eye and ≥20/200 in the fellow eye, and no evidence of active ocular infection. The SAKURA program consisted of two sequentially performed, phase III randomized, double-masked, multinational studies.
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