Letter to the editor: dexamethasone intravitreal implant in the treatment of diabetic macular edema.

Abstract

Dear editor I read “Dexamethasone intravitreal implant in the treatment of diabetic macular edema” published July 2015 by Dugel et al.1 This article is very interesting in terms of providing an outline of the role of inflammation in the pathogenesis of diabetic macular edema and explaining the value of corticosteroids in the treatment of diabetic macular edema. However, I would like to draw your attention to the data presented for ILUVIEN® (fluocinolone acetonide; FAc) in Table 2, which has been presented incorrectly and does not reflect the approved product and dose in Europe. ILUVIEN is indicated in Europe for the treatment of vision impairment associated with chronic diabetic macular edema, considered insufficiently responsive to available therapies2 and is approved in Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Ireland, Italy, Luxembourg, the Netherlands, Norway, Poland, Portugal, Spain, Sweden, and the United Kingdom. ILUVIEN was launched in the United Kingdom in April 2013, Germany in May 2013, and Portugal in January 2015.3 ILUVIEN contains 190 µg of FAc and delivers 0.2 µg of FAc per day. Dugel et al1 presented the data for the 0.5 µg of FAc per day, which was studied in the FAME studies but is not the approved dose in Europe. This needs to be explained to the reader as the data that are relevant to the currently marketed product are those of the 0.2 µg of FAc per day release rate.2,4 Thus, Table 2 presented in Dugel et al has been amended to reflect the data for ILUVIEN. Parameter ILUVIEN Therapeutic indication For the treatment of vision impairment associated with chronic DME, considered insufficiently responsive to available therapies2 Active drug Fluocinolone acetonide (FAc)2 Formulation Non-biodegradable implant (polyimide tube)2 Dose 190 µg of FAc with a daily release rate of 0.2 µg2 Duration of action (months) Up to 36 months. This is underpinned by a pharmacokinetic study in human eyes, which showed that following a single intravitreal injection of ILUVIEN, there was a stable delivery of 0.2 µg of FAc per day that was sustained and therefore detectable after 36 months.2,4 This is complemented by efficacy data that show mean improvements in BCVA and central foveal thickness, from baseline levels, for up to 36 months2,5 License approval Status: a. European countries where an ILUVIEN license has been granted b. European countries where ILUVIEN has been launched a. Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Ireland, Italy, Luxembourg, the Netherlands, Norway, Poland, Portugal, Spain, Sweden, the United Kingdom3 b. United Kingdom, April 2013; Germany, May 2013; and Portugal, January 20153 Phase III clinical trial in DME: FAME studies: FAME A and FAME B2,5 Trial design: a. Description of the FAME studies b. The primary endpoint c. The number of patients studied in the FAME studies a. FAME A and B studies were performed under a single protocol as randomized, double-masked, sham injection-controlled, parallel-group, multicenter studies conducted over a 36-month period and included a pre-planned subgroup analysis to assess efficacy in chronic DME patients2,5 b. The primary endpoint for the FAME studies was 24 months but the studies show ILUVIEN was efficacious for up to 36 months, and this is the basis for the license and indication being approved in Europe. Both FAME A and B trials independently met the primary efficacy endpoint of ≥15 letter improvement in BCVA over baseline c. A total of 956 subjects were randomized2,5 Efficacy (% patients): Chronic DME patients: 15-ETDRS-letter BCVA gain at 3 years 34.0% vs 13.4% (0.2 µg FAc per day vs sham control) of subjects achieved a ≥15 letter improvement from baseline BCVA after 3 years2,5 Ocular safety (% patients): Release rate of 0.2 µg FAc per day vs sham control: a. Elevated IOP a. 38.4% vs 14.1% required IOP-lowering drops2,5 b. Cataract-related adverse events b. 81.7% vs 50.4% where cataract was considered an adverse event2,5 c. Incisional glaucoma surgery (IOP-lowering surgery) c. 4.8% vs 0.5% underwent IOP-lowering surgery2,5 View it in a separate window Abbreviations: DME, diabetic macular edema; BCVA, best-corrected visual acuity; FAME, Fluocinolone Acetonide for Diabetic Macular Edema; ETDRS, Early Treatment Diabetic Retinopathy Study; IOP, intraocular pressure. A number of papers have been published on the pharmacokinetic,4 safety, and efficacy of ILUVIEN,5 and the reader can access the summary of product characteristics for ILUVIEN online.2