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Pauline T Merrill, Yang Yang; Long-Term Safety of Intravitreal Sirolimus for the Treatment of Non-infectious Uveitis (NIU) of the Posterior Segment: 12-Month Results from SAKURA Study 1. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5776.
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The SAKURA trial is a Phase III, randomized, multicenter, 24-month, multinational study assessing the safety and efficacy of intravitreal sirolimus as monotherapy for the treatment of active NIU of the posterior segment. In the 6-month double-masked period of SAKURA Study 1, bimonthly injections of intravitreal sirolimus preserved subjects’ best corrected visual acuity while significantly improving vitreous haze (VH) scores. Here, we report the long-term safety of intravitreal sirolimus during the first 12 months of treatment (the double-masked period combined with the open-label period).
Subjects with active NIU of the posterior segment were randomized in 1:1:1 fashion to receive 44 μg, 440 μg, or 880 μg injections of intravitreal sirolimus, administered every 2 months (Day 1 and Months 2 and 4; double-masked period). Primary efficacy was assessed at Month 5. At Month 6, subjects eligible to receive further intravitreal sirolimus received 880 µg injections every 2 months (Months 6-10; open-label treatment period) under the then current amendment.
Of the 346 randomized and treated subjects, 287 entered the open-label period and completed the VH assessment at Month 12. Of these, 211 received at least 1 injection of intravitreal sirolimus. The most common reasons for premature discontinuation prior to Month 12 were subject withdrawal (n=16), adverse event (n=12), and loss to follow-up (n=11). The adverse events in the open-label period were similar to those reported in the double-masked period. Over the first 12-month treatment period, the most common serious ocular adverse events (≥2%) were worsening of uveitis (7.2%), worsening of choroiditis (4.0%), cataract (3.8%), non-infectious endophthalmitis (2.9%), medication residue (2.3%), and increased intraocular pressure (2.0%). The incidence of post-injection endophthalmitis was 1.2%, all with the 880 μg dose (1 culture positive, 3 culture negative).
Intravitreal sirolimus was associated with a low incidence of serious ocular adverse events over 12 months in this diverse population of subjects with NIU of the posterior segment. The types of adverse events in the open-label period of SAKURA Study 1 were similar to those observed in the double-masked period.
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