Intravitreal Sirolimus Lowers Vitreous Haze Scores, Tapers Corticosteroid Use in SAKURA Study

Patients treated with intravitreal sirolimus experienced both reductions in vitreous haze scores and tapering corticosteroid use associated with their non-infectious uveitis of the posterior segment, according to Alay Banker, MD.

Moreover, Banker added that patients experienced higher levels of success with 440µg doses of the drug than with 44µg doses.

“In the integrated intent-to-treat population, the 440µg dose achieved statistically significant improvements in vitreous haze,” Banker said at the 2017 American Society of Retina Specialists’ annual meeting in Boston, MA. “43% of subjects on corticosteroids at baseline achieved tapering success.”

The results came at the conclusion of the SAKURA program, which was comprised of 2 phase 3 studies assessing the efficacy of every-other-month intravitreal sirolimus injections in subjects with active non-infectious uveitis of the posterior segment. Banker and colleagues measured the proportion of subjects in the study who achieved systemic corticosteroid tapering success in conjunction with improvements in vitreous haze.

Subjects from both studies comprised the intent-to-treat population evaluating intravitreal siroliums every other month 440µg versus 44µg active control, n=208 for each group.

21.2% of patients in the 440µg group versus 13.5% of subjects in the 44µg group in the intergrated intent-to-treat population achieved the primary endpoint of VH=0 at month 5 (p=0.00381).

In the integrated intent-to-taper population, tapering success at month 5 was achieved in 69.6% of patients in the 440µg group, versus 68% of patients in the 44µg group (p=0.9388).

“We do see in the results that there is efficacy even with the lower 44µg dose, though not statistically significant. If you see in the combined studies in the later stage we do see some efficacy, even with the extreme low dose of 44µg,” Banker said.

The findings carry new implications for the practicing clinician, he added.

“The SAKURA study had mean posterior uveitis follow up over 3 years, but I do see it I the future even using it as a primary therapy with patients with lower vitreous haze scores of +2 or +1.5,” Banker said. He presented a case study of a patient with a vitreous haze score of +2.5, who after 3 injections achieved VH=0.

“Since we’ve been following [that patient,] they have not had to receive any other form of therapy for over a year now,” Banker said.

SAKURA 1 included 347 subjects, and SAKURA 2 included 245 subjects. Non-corticosteroid systemic immunosuppressants and topical corticosteroids were discontinued >30 days before baseline, and all subjects already receiving systemic corticosteroids at overall prednisone-equivalent dose >5 mg/day in the intent-to-taper population were tapered off according to protocol schedule from baseline. Intent-to-taper subjects achieving overall prednisone-equivalent dose less than or equal to 5mg/day at month 5 without rescue therapy were classified as systemic corticosteroid tapering successes .

Vitreous haze=0 and systemic corticosteroid tapering success with vitreous haze reduction (VH 0/0.5+) were assessed at month 5.