Intravitreal sirolimus
Combined analysis of two phase 3, randomized, double-blind trials indicates that intravitreal sirolimus improves ocular inflammation (compared with low-dose active control) in patients with noninfectious uveitis.[95]Merrill PT, Clark WL, Banker AS, et al. Efficacy and safety of intravitreal sirolimus for noninfectious uveitis of the posterior segment: results from the sirolimus study assessing double-masked uveitis treatment (SAKURA) program. Ophthalmology. 2020 Oct;127(10):1405-15.
https://www.aaojournal.org/article/S0161-6420(20)30317-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32564920?tool=bestpractice.com
Corticosteroid tapering was reported in approximately 70% of patients receiving the higher dose. Mean changes from baseline intraocular pressure were minimal.[95]Merrill PT, Clark WL, Banker AS, et al. Efficacy and safety of intravitreal sirolimus for noninfectious uveitis of the posterior segment: results from the sirolimus study assessing double-masked uveitis treatment (SAKURA) program. Ophthalmology. 2020 Oct;127(10):1405-15.
https://www.aaojournal.org/article/S0161-6420(20)30317-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32564920?tool=bestpractice.com
Tocilizumab
In one small phase 2 multicenter randomized clinical trial, the majority of patients (>77%) receiving tocilizumab (an interleukin-6 antagonist monoclonal antibody) experienced a positive clinical response (ascertained using a composite end point scoring system to assess the inflammatory outcomes in patients with noninfectious uveitis).[96]Hassan M, Sadiq MA, Ormaechea MS, et al. Utilisation of composite endpoint outcome to assess efficacy of tocilizumab for non-infectious uveitis in the STOP-Uveitis Study. Br J Ophthalmol. 2023 Aug;107(8):1197-201.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10863991
http://www.ncbi.nlm.nih.gov/pubmed/35379598?tool=bestpractice.com
Tocilizumab may be considered in cases of noninfectious uveitis refractory to tumor necrosis factor (TNF)-alpha inhibitors.[60]Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016 Jan-Feb;61(1):1-17.
http://www.ncbi.nlm.nih.gov/pubmed/26164736?tool=bestpractice.com
Janus kinase (JAK) inhibitors
Baricitinib, an oral JAK inhibitor, is undergoing phase 3 trials in patients with chronic anterior antinuclear antibody-positive uveitis.[97]Ramanan AV, Guly CM, Keller SY, et al. Clinical effectiveness and safety of baricitinib for the treatment of juvenile idiopathic arthritis-associated uveitis or chronic anterior antinuclear antibody-positive uveitis: study protocol for an open-label, adalimumab active-controlled phase 3 clinical trial (JUVE-BRIGHT). Trials. 2021 Oct 9;22(1):689.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8502273
http://www.ncbi.nlm.nih.gov/pubmed/34627340?tool=bestpractice.com
Brepocitinib, an investigational oral JAK1 and tyrosine kinase 2 (TYK2) inhibitor, is being evaluated in a phase 2 trial of patients with active noninfectious intermediate, posterior, and panuveitis.[98]ClinicalTrials.gov. A study of brepocitinib in adults with active non-infectious non-anterior uveitis (NEPTUNE). Nov 2024 [internet publication].
https://clinicaltrials.gov/study/NCT05523765
Suprachoroidal triamcinolone
Triamcinolone suprachoroidal injection has been approved by the Food and Drug Administration (FDA) for the treatment of macular edema associated with uveitis.[99]Yeh S, Khurana RN, Shah M, et al. Efficacy and safety of suprachoroidal CLS-TA for macular edema secondary to noninfectious uveitis: phase 3 randomized trial. Ophthalmology. 2020 Jul;127(7):948-55.
https://www.aaojournal.org/article/S0161-6420(20)30011-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32173113?tool=bestpractice.com
Ixekizumab
A phase 4 study to evaluate the efficacy of ixekizumab (an interleukin-17A antagonist monoclonal antibody) for the treatment of noninfectious intermediate, posterior, or panuveitis (or chronic corticosteroid-dependent anterior uveitis that has been resistant to treatment with a classic synthetic disease-modifying anti-rheumatic drug [DMARD]) is currently recruiting.[100]ClinicalTrials.gov. Ixekizumab for the management of refractory non-infectious uveitis: a proof-of-concept study. Oct 2023 [internet publication].
https://clinicaltrials.gov/study/NCT06085079