Assessment of changes in quality of life among patients in the SAVE Study - Sirolimus as therapeutic Approach to uVEitis: a randomized study to assess the safety and bioactivity of intravitreal and subconjunctival injections of sirolimus in patients with non-infectious uveitis

Abstract

BackgroundThe National Eye Institute 39-Question Visual Function Questionnaire (NEI VFQ-39) is an indicator of vision-related quality of life (QoL). The NEI VFQ-39 is used to assess the QoL in patients with non-infectious posterior uveitis, intermediate uveitis, or panuveitis, treated with subconjunctival (SCJ) or intravitreal (IVT) sirolimus as an immunomodulatory therapeutic (IMT) agent, delivered subconjunctivally (SCJ) or intravitreally (IVT) (the SAVE Study). Thirty subjects with non-infectious uveitis were randomized (SCJ:IVT, 1:1) for a prospective clinical trial. The 39-Question Visual Function Questionnaire (VFQ-39) was administered at baseline (BL), month 6 (M6), and month 12 (M12) visits. The survey measures self-reported vision health status for patients with chronic eye disease and assesses the effects of visual impairment on both task-oriented visual function and general health domains. In accordance to the NEI-VFQ Manual, each patient’s questionnaire was converted to a scaled score between 0 (worst) and 100 (best), and median scores were calculated for each of the subcategories and overall composite score at BL, M6, and M12. Wilcoxon signed-rank test was performed.ResultsTwenty-six patients completed the VFQ-39 at BL and M6, whereas 23 patients completed it at M12. Patients showed a significant improvement in pooled composite scores from BL to M6 and BL to M12. Analysis by treatment groups showed that intravitreal injection of sirolimus is better tolerated.ConclusionsSirolimus has demonstrated bioactivity as an IMT and corticosteroid-sparing agent to treat non-infectious uveitis. Patients receiving intravitreal injection of sirolimus showed overall improvement of vision-related health while those receiving subconjunctival injections did not. Larger randomized control trials with sirolimus are indicated to validate these results.Trial registrationClinicalTrials.gov: NCT00908466Electronic supplementary materialThe online version of this article (doi:10.1186/s12348-015-0044-1) contains supplementary material, which is available to authorized users.

A Comprehensive Review of mTOR-Inhibiting Pharmacotherapy for the Treatment of Non-Infectious Uveitis

“…The use of intravitreal and subcutaneous administration of sirolimus was investigated in two prospective studies. The SAVE study [40,41,42] was a randomised open label trial comparing two monthly subcutaneous vs intravitreal sirolimus with a primary endpoint at 6 months, and then a further 6 months extension during which treatment could be continued at the investigator's discretion. The primary efficacy outcome was a reduction of vitreous haze by 2 points (in those with active uveitis at baseline), or the maintenance of no clinical vitreous haze (in those with inactive disease at baseline).…”

New therapies in development for the management of non‐infectious uveitis: A review

“…The 1‐year outcome of the SAVE study was positive with 70% of the patients showing a more‐than‐two‐step reduction in the vitreous haze score . The subjects in the SAVE study also showed improvement in their quality of life as assessed by the visual function questionnaire . The favourable outcome from the SAVE study was followed by the conduct of the Sirolimus as a Therapeutic Approach for Uveitis: Protocol 2 (SAVE‐2) study.…”

“…197 The subjects in the SAVE study also showed improvement in their quality of life as assessed by the visual function questionnaire. 198 The favourable outcome from the SAVE study was followed by the conduct of the Sirolimus as a Therapeutic Approach for Uveitis: Protocol 2 (SAVE-2) study. SAVE-2 was a phase 2 randomized open-label clinical trial evaluating two different doses of IVT sirolimus (440 μg given monthly and 880 μg given bimonthly) in patients with NIU.…”

Efficacy and safety of intravitreal anti‐tumour necrosis factor drugs in adults with non‐infectious uveitis – a systematic review

“…; Vigil et al. ). In experimental autoimmune uveitis, intravitreal anti‐TNF administration suppresses ocular inflammation particularly inhibiting macrophage activation that suppresses structural damage and prevents functional loss.…”

“…Side-effects related to systemic administration have led to the investigation of intravitreal route of administration, as an option that could curtail some of these unwanted effects while preserving therapeutic efficacy (Levy-Clarke et al 2014;Pascual-Camps et al 2014). This route of drug delivery has been well established in uveitis treated with corticosteroids (Kane et al 2008;Taylor et al 2012;Kempen et al 2015a,b;Reddy et al 2016), anti-vascular endothelial growth factor (VEGF), (Androudi et al 2010;Tempest-Roe et al 2013) or sirolimus (Ibrahim et al 2015;Vigil et al 2015). In experimental autoimmune uveitis, intravitreal anti-TNF administration suppresses ocular inflammation particularly inhibiting macrophage activation that suppresses structural damage and prevents functional loss.…”