Changes in vitreous haze over time with intravitreal sirolimus in noninfectious posterior-segment uveitis (NI-PSU): results of SAKURA Study 1

Purpose To evaluate changes in vitreous haze (VH) scores over time in in SAKURA Study 1, a randomized, double-masked, multicenter, international phase III study of subjects with active NI-PSU. Methods 347 subjects with active NI-PSU (VH score ≥1.5+) were randomized to intravitreal sirolimus (44, 440, or 880 µg), given every 2 months. VH scores were assessed at Week 2 and Months 1–5. Results At baseline, the mean (SD) VH scores were 1.9 (0.44) for the 440 µg group and 1.9 (0.50) for the 44 µg group. The risk:benefit profile was most favorable with 440 µg: Significantly more patients achieved a VH score of 0 at Month 5 (the primary endpoint) with 440 µg vs 44 µg (22.8% vs 10.3%; p=.025). 440 µg was also significantly more effective than 44 µg in achieving a VH score of 0/0.5+ (51.8% vs 35%; p=.012). Improvement was seen as early as Week 2 with 440 µg (22.8% with VH=0/0.5+) and continued improvement with this dose was seen at every analysis visit (36.0%, 40.4%, 49.1%, 42.1%, and 51.8% with VH=0/0.5+ at Months 1–5, respectively). Conclusion Intravitreal sirolimus 440 μg significantly improved inflammation in this diverse NI-PSU population. VH improvement was seen as early as 2 weeks after the first injection and continued through Month 5. Treatment with intravitreal sirolimus 440 µg appears to be effective in treating NI-PSU, with a balanced safety profile. Commercial interest