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Sirolimus can reduce vitreous haze in patients with non-infectious uveitis
The results of the SAKURA program demonstrated a 440 µg dose of intravitreal sirolimus was more effective in reducing vitreous haze scores to 0.
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A higher proportion of patients with non-infectious uveitis experienced a reduction of their vitreous haze scores to 0 at 5 months after receiving a 440 µg dose of intravitreal sirolimus compared with control subjects receiving a 44 µg dose of sirolimus, according to a study.
Two phase 3 studies found 440 µg of intravitreal sirolimus (Santen), a locally delivered mTOR inhibitor, effectively reduced vitreous haze scores to 0, with fewer adverse events, at 5 months’ follow-up for patients with non-infectious uveitis of the posterior segment, Pauline T. Merrill, MD, told Ocular Surgery News.
“Eligible patients were randomized into one of three active treatment arms (44 µg, 440 µg and 880 µg). The SAKURA program demonstrated that the [intravitreal] sirolimus 440 µg dose is the most effective and safest dose tested for the reduction of intraocular inflammation as measured by vitreous haze in patients with non-infectious uveitis of the posterior segment,” Merrill said.
Reduction of vitreous haze
SAKURA 1 and 2 are two phase 3 randomized, double-masked, multinational studies that evaluated the safety and efficacy of intravitreal injections of 440 µg and 880 µg of sirolimus compared with 44 µg (active control) of sirolimus for the treatment of non-infectious uveitis of the posterior segment. The primary outcome of the study was reduction of vitreous haze to a 0 score.
Subjects were included in the studies if they had a diagnosis of active non-infectious uveitis in the posterior segment, a vitreous haze score of 1.5+ or higher in the study eye, best corrected visual acuity of 19 ETDRS letters or greater (20/400) in the study eye, and vision of 20/200 or better in the fellow eye, according to Merrill.
The SAKURA 1 study included 347 patients randomized to one of the three dosing arms.
“Following the results from SAKURA 1, SAKURA 2 was amended to terminate investigation of the 880 µg dose,” Merrill said.
In the integrated population, a higher proportion of patients receiving a 440 µg intravitreal dose of sirolimus (21.2%) experienced a reduction of their vitreous haze scores to 0 at 5 months compared with the control subjects receiving a 44 µg intravitreal dose of sirolimus (13.5%).
Multiple measures of inflammation
In a post hoc analysis of patients in the SAKURA program with multiple measures of inflammation, the 440 µg dose group had a statistically significant advantage in reducing vitreous haze scores to 0 at 5 months in study 1, study 2 and the integrated population, Merrill said.
According to Merrill, multiple measures of inflammation were defined as vitreous haze of 1.5+ or greater and one or more additional characteristics of inflammation: requirement for systemic corticosteroids (prednisone-equivalent dose of 7.5 mg/day or higher; BCVA of 75 ETDRS letters or less; and/or presence of macular edema (central retinal thickness of 300 µm or greater on OCT).
“Overall, there was a low incidence of adverse events typically associated with other treatments for non-infectious uveitis of the posterior segment, including corticosteroid therapy, and ocular serious adverse events observed with [intravitreal] sirolimus (440 µg) were similar to those in the active control group. Based on these results, Santen plans to file a [new drug application] with the FDA for the 440 µg dose in the first half of this year,” she said. – by Robert Linnehan
- Reference:
- Merrill PT. Study assessing double-masked uveitis treatment study 2. Presented at: Retina World Congress; Feb. 23-26, 2017; Fort Lauderdale, Fla.
- For more information:
- Pauline T. Merrill, MD, can be reached at Illinois Retina Associates, Rush Medical Center, 1725 West Harrison Ave., Suite 915, Chicago, IL 60612; email: pauline.merrill@gmail.com.
Disclosure: Merrill reports she received grants, personal fees and non-financial support from Santen during the conduct of the study and receives grants and personal fees from AbbVie.