Outcomes of treatment with sirolimus for non-infectious uveitis: a meta-analysis and systematic review

Vicente Lorenzo O Cabahug,¹ Harvey S Uy,^1,2 Ellen Yu-Keh,¹ Kristine Joy D Sapno<sup>3

1</sup>St Luke’s Medical Center, Quezon City, Philippines; ²University of the Philippines, Manila, Philippines; ³University of Santo Tomas Hospital, Manila, Philippines

Background: Uveitis 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).
Objective: The aim of this review was to assess and summarize the updated evidence on the outcomes of treatment with sirolimus for NIU.
Materials and methods: Two 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.
Results: Seven 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.
Conclusion: This 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.

Keywords: non-infectious uveitis, immunosuppression, corticosteroid-sparing, sirolimus, mTOR inhibitors, uveitis treatment, vitreous haze