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Ocular tolerability and efficacy of intravitreal and subconjunctival injections of sirolimus in patients with non-infectious uveitis: primary 6-month results of the SAVE Study.

ABSTRACT: BACKGROUND:The purpose of this study is to evaluate the ocular tolerability and efficacy of sirolimus administered as subconjunctival or intravitreal injections in patients with non-infectious uveitis. Sirolimus as a Therapeutic Approach for Uveitis (SAVE) is a prospective, randomized, open-label, interventional study. Thirty patients were enrolled and randomized in 1:1 ratio to receive either intravitreal injections of 352 ?g sirolimus or subconjunctival injections of 1,320 ?g at days 0, 60, and 120, with primary endpoint at month 6. RESULTS:At month 6, all subjects with active uveitis at baseline showed reduction in vitreous haze of one or more steps. Forty percent of subjects showed reduction of two steps or more of vitreous haze (four in each group), and 60% showed a reduction of one-step vitreous haze (seven in group 1 and five in group 2). Changes in the inflammatory indices were statistically significant (p < 0.05) in both study groups. Thirty percent of patients gained one or more lines of visual acuity, 20% lost one or more lines, and 50% maintained the same visual acuity. There were no statistically significant differences between the two study groups at month 6. No serious adverse events were found to be related to the study drug. CONCLUSION:Local administration of sirolimus, either intravitreally or subconjunctivally, appears to be safe and tolerable. No drug-related systemic adverse events or serious adverse events were noted. Sirolimus delivered as either an intravitreal or subconjunctival injection has demonstrated bioactivity as an immunomodulatory and corticosteroid-sparing agent in reducing vitreous haze and cells, improving visual acuity, and in decreasing the need for systemic corticosteroids.

SUBMITTER: Nguyen QD

PROVIDER: S-EPMC3610181 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Ocular tolerability and efficacy of intravitreal and subconjunctival injections of sirolimus in patients with non-infectious uveitis: primary 6-month results of the SAVE Study.

Nguyen Quan Dong QD Ibrahim Mohamed A MA Watters Anthony A Bittencourt Millena M Yohannan Jithin J Sepah Yasir J YJ Dunn James P JP Naor Joel J Shams Naveed N Shaikh Ovais O Leder Henry Alexander HA Do Diana V DV

Journal of ophthalmic inflammation and infection 20130211 1

<h4>Background</h4>The purpose of this study is to evaluate the ocular tolerability and efficacy of sirolimus administered as subconjunctival or intravitreal injections in patients with non-infectious uveitis. Sirolimus as a Therapeutic Approach for Uveitis (SAVE) is a prospective, randomized, open-label, interventional study. Thirty patients were enrolled and randomized in 1:1 ratio to receive either intravitreal injections of 352 μg sirolimus or subconjunctival injections of 1,320 μg at days 0 ...[more]

PMID: 23514595

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Project description:PURPOSE:To determine the efficacy and safety of repeated intravitreal and subconjunctival administrations of sirolimus in patients with noninfectious uveitis at 1 year in the Sirolimus as a Therapeutic Approach UVEitis (SAVE) Study. METHODS:Open-label, prospective, and randomized interventional clinical trial in which 30 patients with noninfectious intermediate, posterior, or panuveitis were randomized 1:1 to receive sirolimus 352-?g intravitreal or 1320-?g subconjunctival. Sirolimus was administered at days 0, 60, and 120. At month 6, all subjects were allowed to receive sirolimus at intervals greater than or equal to 2 months and until month 12. Changes in vitreous haze (VH), visual acuity (VA), and retinal thickness at month 12 were compared with baseline. RESULTS:Of patients with active uveitis at baseline (n = 20), 70% showed greater than or equal to 2 steps reduction of VH at month 12 (P < 0.05), 88% (n = 7) of patients with inactive uveitis at baseline showed either no change or reduction of VH to no haze, 36% (n = 10) of all patients (n = 28) gained greater than or equal to one line of VA, 21% (n = 6) lost greater than or equal to 1 line, and 43% (n = 12) showed no change. At the end of 1 year, no statistical differences in efficacy were found between intravitreal and subconjunctival groups. No serious adverse events were determined to be secondary to sirolimus. CONCLUSIONS:Repeated subconjunctival/intravitreal injections of sirolimus appear to be tolerated by patients with noninfectious uveitis over 12 months. Results from the index study suggest that sirolimus may provide benefits to patients with uveitis. Both intravitreal and subconjunctival routes demonstrate similar bioactivity/efficacy. The intravitreal route, however, was better tolerated. TRANSLATIONAL RELEVANCE:The SAVE Study illustrates for the first time the application of local formulations of sirolimus in non-infectious intermediate, posterior, and pan-uveitis. Subconjunctival/Intravitreal sirolimus may help to control inflammation while offering better tolerability/safety profiles than systemic therapies, including immunosuppressants and corticosteroids.

Project description:BackgroundUveitis is a group of intraocular inflammatory diseases whose primary treatment involves immunosuppression. Although corticosteroids (CSs) remain the mainstay therapy, sirolimus is among the recently studied immunomodulatory drugs for treating noninfectious uveitis (NIU).ObjectiveThe aim of this review was to assess and summarize the updated evidence on the outcomes of treatment with sirolimus for NIU.Materials and methodsTwo reviewers conducted a systematic search on November 5, 2018, of electronic databases (EMBASE, MEDLINE, and The Cochrane Library) and clinical trial registers having no restrictions on language or publication date. The primary outcome was uveitis activity as measured by vitreous haze (VH), while the secondary outcomes included central macular thickness (CMT), best-corrected visual acuity (BCVA), CS-sparing effect, IOP elevation, and other adverse events. A meta-analysis was conducted on selected studies with appropriate clinical and methodological homogeneity.ResultsSeven studies were included and reviewed. Four randomized clinical trials were eligible for meta-analysis: SAVE 2013, One-year outcomes of the SAVE study, SAVE 2 2016, SAKURA 2016. The pooled proportions of inflammation control (VH improvement) were 38% (95% CI 16.19%-62.66%) during a 6-month follow-up and 49.97% (95% CI 16.19%-83.03%) during a 6- to 12-month follow-up with the latter showing a significantly higher response rate (p=0.0472). BCVA improvement was 62.2% (95% CI 33.17%-87.11%) during a 6-month follow-up and 56.86% (95% CI 20.91%-89.05%) during a 6- to 12-month follow-up with no significant difference between the two (p=0.3705). Increased IOP remained at 7.11% (95% CI 3.46%-12.68%) for both a 6-month follow-up and up to a 12-month follow-up duration. The CS-sparing effect of sirolimus was also well demonstrated. A reduction in CMT was observed, and only minor drug-related adverse events were reported in all the studies reviewed.ConclusionThis review provided evidence that sirolimus is a promising treatment option for controlling inflammatory activity, improving visual acuity, and sparing CS use with minor adverse events for NIU.

Dataset Information

Ocular tolerability and efficacy of intravitreal and subconjunctival injections of sirolimus in patients with non-infectious uveitis: primary 6-month results of the SAVE Study.

Publications

Ocular tolerability and efficacy of intravitreal and subconjunctival injections of sirolimus in patients with non-infectious uveitis: primary 6-month results of the SAVE Study.

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