Author: Justus Garweg
Co-authors: Peter Rossing, Stefan D. Anker, Takeshi Osonoi, Bertram Pitt, Sylvia E. Rosas, Luis Miguel Ruilope, Dalong Zhu, Meike Brinker, David Finis, Sergio Leal, Thomas Schmelter, George Bakris
AbstractPurpose: Finerenone is a potent and selective mineralocorticoid receptor (MR) antagonist that slowed progression of chronic kidney disease (CKD) and reduced risk of cardiovascular outcomes versus placebo in patients with CKD and type 2 diabetes (T2D) in the FIDELIO-DKD and FIGARO-DKD phase 3 trials. MR overactivation is involved in the pathogenesis of diabetic retinopathy (DR). This study aimed to evaluate potential benefits of oral finerenone on progression of DR.
Setting/Venue: Two studies of identical design (ReFineDR and DeFineDR) retrospectively collected observational data from patients with DR in FIDELIO-DKD/FIGARO-DKD at selected centres.
Methods: Eligible patients had a routine ophthalmological examination showing non-proliferative DR (NPDR) in ≥1 eye performed 6 months prior to 1 month post-randomization in FIDELIO-DKD/FIGARO-DKD, and ≥1 subsequent ophthalmological assessment. Patients with diabetic macular edema (DME), proliferative DR (PDR), any other retinal disease in ≥1 eye that might interfere with study objectives (e.g. neovascular age-related macular degeneration or retinal vein occlusion), or prior/planned ocular interventions (retinal laser treatment, intravitreal injection or vitrectomy), were excluded. Inclusion was blinded to FIDELIO-DKD/FIGARO-DKD treatment assignment. The primary endpoint was occurrence of vision-threatening events (VTE; anterior segment neovascularisation, DME or PDR) at 2 years.
Results: Overall, 134 patients had received finerenone and 110 had received placebo; 68.7% and 71.8% had mild/moderate NPDR, 3.0% and 10.0% had severe NPDR, and 27.6% and 15.5% had NPDR of unknown severity. Mean baseline glycated haemoglobin (HbA1c) was similar between groups (finerenone: 8.25 [standard deviation (SD) 1.41]; placebo: 8.18 [SD 1.34]). At 2 years, 5 (3.7%) and 7 (6.4%) patients in the finerenone and placebo groups had VTE in ≥1 eye (difference -0.026, 95% CI -0.082 to 0.029, p=0.3550). The number of VTEs increased after 2 years, with trends in Kaplan–Meier estimated cumulative incidence probabilities (post hoc) favouring finerenone at 30 months (difference -0.109, 95% CI -0.202 to -0.016) and 36 months (difference -0.118, 95% CI -0.229 to -0.007). Results were generally consistent across components of the primary endpoint. Numerical trends in favour of finerenone were observed in the subgroups of patients with baseline HbA1c ≤7.5% and HbA1c >7.5%. Fewer finerenone vs placebo patients had required ocular interventions (4 [3%] vs 17 [15.5%] at 2 years), with trends for favourable probabilities at 24, 30, and 36 months (post hoc).
Conclusions: Both studies showed consistent positive trends for finerenone in the prevention of progression of NDPR, both overall and across subgroups by baseline HbA1c. Further research is required to confirm this effect.
JGG acts as an advisor and speaker to several pharmaceutical companies (AbbVie, Bayer, Novartis, Roche) and contributes to several clinical studies. The author has no conflicting interests with the findings that are presented in this report.
PR discloses receiving honorarium from Bayer AG which was paid to his institution, receiving research support and personal fees from AstraZeneca and Novo Nordisk, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astellas Pharma Inc., and personal fees given to Steno Diabetes Center Copenhagen from Bayer, Boehringer Ingelheim, Eli Lilly and Company, Gilead, Merck, Merck Sharp and Dohme, Mundipharma, Sanofi, and Vifor Pharma.
SDA discloses grants for IIT from Vifor Int and Abbott Vascular, consultancy fees from Cardiac Dimensions, ad hoc consultancy fees from Amgen, Respicardia, Brahms, and Cordio, fees for trial steering committee work from Vifor and Abbott Vascular, trial steering committee work with Bayer AG, Boehringer Ingelheim, Bioventrix, Janssen, V-Wave, and Occlutech, Registry Steering Committee work with Sevier, ad hoc advisory board with AstraZeneca, and cancer cachexia focused research company: Chair advisory board & share holder as founder of Actimed.
TO discloses no conflicts of interest in relation to this project.
BP discloses consultancy fees from Bayer, AstraZeneca, KBP Pharmaceuticals, Sarfez, scPharmaceuticals, SQinnovations, G3phrmaceuticlas, Cereno Scientific, Relypsa/Vifor, Ardelyx, Tricida, Sanofi/Lexicon, Phasbio, Boehringer Ingelheim, and Brainstrom Medical, issued US patent 9931412 for site specific delivery of Eplerenone to the myocardium, provisional patent US 63/045,784 (pending; histone-acetylation-modulating agents for the treatment and prevention of organ injury), and stock options with KBP Pharmaceuticals, Sarfez, scPharmaceuticals, SQinnovations, G3phrmaceuticlas, Cereno Scientific, Relypsa/Vifor, Ardelyx, Tricida, and Brainstrom Medical.
SER discloses research support to Joslin Diabetes Center for clinical trials from Bayer Healthcare and AstraZeneca.
LMR discloses consultancy fees from Bayer AG.
MB, DF, and TS are employees of Bayer AG and may hold stock and/or stock options with Bayer AG
SL is an employee of Bayer Consumer Care AG and may hold stock and/or stock options with Bayer AG.
GB discloses funding for the FIDELITY clinical trial paid directly to University of Chicago Medicine from Bayer AG, consulting fees from Merck, Alnylam, and Ionis, involvement with the FLOW trial Steering Committee with fees paid to University of Chicago from Novo Nordisk, principal investigator of the REFRESH trial with fees paid to University of Chicago from Quantum Genomics, acting as a steering committee member InREGEN with fees paid to University of Chicago.
Professor Dalong Zhu discloses fee for advisor boards, scientific presentation and travel support from AstraZeneca and Bayer.