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SAKURA Study 1: Intravitreal sirolimus safe for noninfectious uveitis of posterior segment
Eyes with the worst vision at baseline had the greatest improvement at 5 months.
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A study showed intravitreal sirolimus may be a viable alternative to corticosteroids in the long-term treatment of chronic noninfectious uveitis of the posterior segment.
A 440 µg injection yielded the greatest reduction in inflammation. The greatest visual gains occurred in eyes with the worst visual acuity at baseline.
Sunil K. Srivastava, MD, presented results of Santen’s first Study Assessing Double‐Masked Uveitis Treatment (SAKURA Study 1) at the American Academy of Ophthalmology meeting in Chicago.
In a subsequent interview with Ocular Surgery News, Srivastava discussed the high safety profile of intravitreal sirolimus compared with corticosteroids.
Sunil K. Srivastava
“[Sirolimus] is a localized therapy to the eye, so it avoids having to use systemic immunosuppressive medications, which can have some side effects,” Srivastava said. “It can avoid local injections of corticosteroids, which don’t have systemic side effects but have a high risk of ocular side effects like cataracts and glaucoma. So, the potential advantage of intravitreal sirolimus is that you can control inflammation locally without using systemic medications, without the local risk of cataracts or glaucoma.”
Study results were also presented at the European Society of Cataract and Refractive Surgeons meeting in London.
Patients and protocols
The phase 3 multicenter, randomized, double-masked trial was designed to assess the safety and efficacy of 440 µg and 880 µg intravitreal injections of sirolimus compared with 44 µg injections in the treatment of noninfectious uveitis in the posterior segment.
Patients were randomized to receive a 44-µg dose of sirolimus (117 patients), a 440-µg dose (114 patients) or an 880-µg dose (116 patients) at baseline, 2 months and 4 months.
An open-label arm comprised patients who received the 880 µg dose at 6, 8 and 10 months and received as-needed injections thereafter starting at month 12. The final study endpoint is 24 months.
Sixty-nine patients entered the study with a baseline systemic corticosteroid dose of at least 7.5 mg per day; of those patients, 22 received 44 µg, 26 received 440 µg and 21 received 880 µg. Steroids were tapered off rapidly starting at day 1.
The primary outcome measure was the proportion of patients with a vitreous haze score of 0 in study eyes at 5 months.
Key secondary measures were vitreous haze scores of 0 or 0.5+ at month 5 in study eyes; vitreous haze scores of 0 or an improvement of at least 2 units at 5 months in study eyes; and corticosteroid tapering success at 5 months.
Results and conclusions
At 5 months, 10.3% of patients in the 44 µg group, 22.8% of patients in the 440 µg group and 16.4% of patients in the 880 µg group met the primary endpoint of a vitreous haze score of 0. The between-group difference was statistically significant for 440 µg vs. 44 µg.
“When looking at the vitreous haze scores, there was a statistically significant improvement in those patients who got 440 µg vs. those in the 44 µg group. Both groups had some improvement in their vitreous haze scores, but those in the 440 µg group had a greater improvement than those in the 44 µg group,” Srivastava said.
Tapering success was 63.6% in the 44 µg group and 76.9% in the 440 µg group; 52.6% of patients in the 440 µg group had vitreous haze scores of 0 or 0.5+ (P = .008), Srivastava said.
Among 149 eyes with baseline best corrected visual acuity of 20/40 or better, mean gains were 1 line in the 44 µg and 440 µg groups. Among 168 eyes with baseline BCVA worse than 20/40, the mean gain was 5 letters in the 44 µg group and 5.5 letters in the 440 µg group. Among 46 eyes with baseline BCVA worse than 20/100, the mean gain was 4.5 letters in the 44 µg group and 10.5 letters in the 440 µg group.
“The problem is that this is a small number, so you can’t really make a big statistical comparison,” Srivastava said.
All three groups had a low incidence of serious ocular events such as IOP spikes, cataract formation and glaucoma.
“[At the higher doses], there were a couple of cases of what they call pseudoendophthalmitis, which means not real, true infection but an event with some inflammation after the injection. That was mainly seen in the 880 µg group. But there were no true events of infection that were noted in the study,” Srivastava said.
Central retinal thickness decreased in 29 eyes with macular edema at baseline that received 440 µg injections. – by Matt Hasson
For more information:
Sunil K. Srivastava, MD, can be reached at Cleveland Clinic, 9500 Euclid Ave., Mail Code i32, Cleveland, OH 44195; email: srivass2@ccf.org.Disclosure: Srivastava reports he is a consultant for Allergan, Bausch + Lomb and Santen.