<p>Effectiveness of 190 μg Fluocinolone Acetonide and 700 μg Dexamethasone Intravitreal Implants in Diabetic Macular Edema Using the Area-Under-the-Curve Method: The CONSTANT Analysis</p>

Abstract

Purpose: Calculations of area-under-the-curve (AUC) provide the average letters gained across the entire treatment period, which may be a better estimate of long-term effectiveness than single time-point outcomes, particularly when it comes to sustained-release therapies. Materials and Methods: The AUC method was used to compare the efficacy of the 0.2 µg/day fluocinolone acetonide (total dose of 0.19 mg; FAc) and dexamethasone (DEX) 700 µg implants based on published data from their respective Phase 3 FAME (Fluocinolone Acetonide for Macular Edema) and MEAD pivotal clinical trials in diabetic macular edema (DME). Best-corrected visual acuity (BCVA) letter scores were collated from the FAME trial and compared with those reported in MEAD. The trapezoidal rule was then used to calculate AUC, based on BCVA letter score, from baseline to Month 36 (FAME)/Month 39 (MEAD) and presented as an overall mean visual acuity change per day. Results: Treatment with either the FAc or DEX implant resulted in an improved BCVA over the treatment period compared with sham. This effect was statistically greater (p=0.029) for the FAc implant than the DEX implant (5.2 vs 3.5 letters/day, respectively) and even greater in the recurrent DME subgroup (p<0.001; 6.9 vs 3.5 letters/day, respectively). Conclusion: Although direct comparisons between trial cohorts cannot be performed, this analysis indicated that, in their respective pivotal clinical trial cohorts, treatment with the FAc implant provides better long-term visual acuity outcomes and a lower treatment burden than achieved with the DEX implant.

Efficacy of 0.19 mg Fluocinolone Acetonide Implant in Non-infectious Posterior Uveitis Evaluated as Area Under the Curve

“…FAc implant is approved in Europe for the treatment of diabetic macular edema (DME) and NIU-PS [ 5 ]. The efficacy of the implant has been recently evaluated with an area under the curve (AUC) approach in eyes with DME [ 6 ]. No such analysis has been employed in the uveitis field.…”

<p>Comment on ’Effectiveness of 190 μg Fluocinolone Acetonide versus 700 μg Dexamethasone Intravitreal Implants in Diabetic Macular Edema Using the Area-Under-the-Curve Method: The CONSTANT Analysis’ [Response to Letter]</p>

“…In summary, we do acknowledge that the AUC analysis does have limitations and that these have been acknowledged in the manuscript and are based on the retrospective nature of the analysis as well as the comparison of different study protocols and patients. 6 However, the 190 µg fluocinolone acetonide implant's constant and near zeroorder drug release kinetics 7 means it is less affected by the timing of appointments and delayed injections, and is a key design feature that has long-term benefits for patients with diabetic macular edema.…”

<p>Letter to the Editor Regarding the “Effectiveness of 190 μg Fluocinolone Acetonide and 700 μg Dexamethasone Intravitreal Implants in Diabetic Macular Edema Using the Area-Under-the-Curve Method: The Constant Analysis” Article [Letter]</p>

“…In a recent edition of Clinical Ophthalmology, Zarranz-Ventura and Mali presented 1 an area-under-the-curve (AUC) analysis that directly compared the best corrected visual acuity (BCVA) improvements in the pivotal diabetic macular edema (DME) trials (FAME and MEAD) for the fluocinolone acetonide implant (Iluvien) and the dexamethasone implant (Ozurdex). They concluded that patients in FAME had superior BCVA improvement over the course of 36 months.…”