Outcomes of treatment with sirolimus for non-infectious uveitis: a meta-analysis and systematic review
Received 16 December 2018
Accepted for publication 22 February 2019
Published 18 April 2019 Volume 2019:13 Pages 649—669
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Ms Justinn Cochran
Peer reviewer comments 3
Editor who approved publication: Dr Scott Fraser
Vicente Lorenzo O Cabahug,1 Harvey S Uy,1,2 Ellen Yu-Keh,1 Kristine Joy D Sapno3
1St 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
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