CONTEXT: Peer reviewed paper reviewing standard treatments for non-infectious uveitis, which is a major cause of vision loss. This data review includes analysis from both RCT and RWR studies to give an overall picture of safety and efficacy. However their conclusions demonstrate the heavy reliance on RCT data, with very little evidence of real-world effectiveness, patient acceptability and overall quality of life.
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1. “In this comprehensive review, we discuss the efficacy, safety and patient acceptability of injectable fluocinolone acetonide implants (FAi) (0.18 mg and 0.19 mg inserts) in NIU-PS, including phase 3 clinical trial and real-world data.”
2. “There are several different long-acting FAi drug delivery systems for NIU-PS:. Long-acting, surgically placed FAi implants were developed and investigated in NIU-PS, initially with 2.1 mg and 0.59 mg implants.7–9 Subsequently, the FDA approved in 2005 a 0.59 mg FAi (providing initial release of 0.6 μg/day, reducing to steady state of 0.3–0.4 μg/day) (Retisert, Bausch and Lomb, Rochester, NJ, USA) non-biodegradable implant, inserted via pars plana incision.10 The 0.59 mg implant was compared to systemic treatment in NIU-PS in the multi-centre uveitis treatment trial11 and furthermore against standard of care in chronic NIU-PS by Pavesio et al.12 Studies demonstrated effective control of inflammation in chronic NIU but high rates of raised intraocular pressure (IOP), need for IOP-lowering procedures and cataract requiring surgery, were observed.9,11,12 In one large study in NIU, topical IOP-lowering medications were required in 74.8% of implanted eyes, and IOP-lowering surgeries were performed in 36.6% of implanted eyes by 36 months follow-up.13. Subsequently, revised-dose and injectable intravitreal inserts (0.18 and 0.19 mg) were designed to improve safety and to facilitate insertion, patient comfort and convenience using injection applicators suitable for an office-based setting.”
3. “Fluocinolone is a synthetic fluorinated glucocorticoid ((6a, 11b, with low solubility in aqueous.15,16 A human pharmacokinetic study showed that following a 0.2 μg/day insert, peak drug levels in the aqueous (slightly >2ng/mL) were sustained for approximately 3 months, followed by steady-state levels from around 6 months (0.5–1.0ng/mL) for 36 months.17 Therefore, a 0.2 μg/day insert provides stable long-term release of FA, the drug then diffusing from vitreous into retina/choroid and other ocular tissues.17,18 There was no detectable FA in plasma samples from day 1 to month 36.17. ILUVIEN, a 0.19mg implant, is a non-biodegradable cylinder containing a FA acetonide drug core.19 The insert releases FA at a rate of 0.2 μg/day for up to 36 months.19 ILUVIEN was approved in 2019 in Europe and the UK for prevention of relapse of NIU-PS.20. The FDA approved YUTIQ, a 0.18 mg intravitreal implant comprising a drug core within a non-bioerodible polyimide tube, for the treatment of NIU-PS in 2018.”
4. “The implant releases 0.25 μg/day FA initially, and subsequently is reported as a 0.2 μg/day implant, lasting up to 36 months.21. Both implants are produced in pre-loaded sterile 25-gauge applicators with a needle length of 8.5 mm for ILUVIEN and 3.5 mm for YUTIQ, for intravitreal injection under local anaesthesia (office-based procedure).”
5. “Throughout 36 months of follow-up, the favourable efficacy outcomes compared with sham injection continued.26 The FAi treatment group had significantly fewer recurrences, required fewer adjunctive treatments, had significantly longer recurrence-free durations and a higher rate of CME resolution compared with sham-treated eyes.”