EFFECT OF FINERENONE TREATMENT DISCONTINUATION ON KIDNEY AND CV OUTCOMES IN PATIENTS WITH CKD AND T2D: A FIDELITY SUBANALYSIS

Introduction:

Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, has been shown to reduce the risk of kidney disease progression and cardiovascular (CV) events compared with placebo in people with chronic kidney disease (CKD) and type 2 diabetes (T2D) included in the FIDELITY prespecified pooled analysis of the phase III FIDELIO-DKD and FIGARO-DKD trials. This post hoc FIDELITY subanalysis aimed to assess the effect of finerenone treatment discontinuation on kidney and CV outcomes as well as to explore predictors of premature treatment discontinuation.

Methods:

The FIDELITY dataset included people with CKD and T2D treated with optimized renin–angiotensin system inhibitor therapy, randomized 1:1 to finerenone or placebo. Baseline characteristics including age, sex, race, region, estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), serum potassium, and use of beta blocker and sodium-glucose co-transporter-2 inhibitors were first identified and then assessed as predictors of treatment discontinuation in a multivariate Cox model selection. Additionally, Cox models, including the interaction between the baseline characteristics and treatment, were developed to investigate potential differences in the effect of baseline characteristics on discontinuation between the treatment groups. Stratified Cox models were used to assess efficacy outcomes using treatment discontinuation as a time-varying covariate. Composite kidney (kidney failure, sustained ≥57% eGFR decrease from baseline over ≥4 weeks, or kidney-related death) and CV (CV death, nonfatal stroke, nonfatal myocardial infarction, or hospitalization for heart failure) outcomes were analyzed.

Results:

Of 12,990 participants included in the full analysis set, 2889 (22.2%) prematurely discontinued treatment and 10,101 (77.8%) remained on-treatment. In the finerenone arm, the risk of treatment discontinuation was increased in participants with older age, Black and White race, with lower eGFR, higher UACR and higher serum potassium (Table 1). Based on p-values for interaction, no significant differences in the effect of baseline characteristics on discontinuation were detected between treatment groups for any of the baseline characteristics assessed. The effect of finerenone vs placebo on the composite kidney outcome appeared to be reduced after treatment discontinuation (hazard ratio [HR]=0.82; 95% confidence interval [CI] 0.66–1.02) compared with the time on-treatment (HR=0.65; 95% CI 0.54–0.78; p=0.0959; Fig 1). Similar results were observed for the composite CV outcome; a numerical decrease in the treatment effect of finerenone was seen after discontinuation of treatment (HR=0.93; 95% CI 0.79–1.09) vs the time on-treatment (HR=0.79; 95% CI 0.70–0.88; p=0.0960).

Conclusions:

Treatment discontinuation rates were low in the finerenone group and were comparable with placebo. The risk of discontinuation increased with older age, Black and White race, lower eGFR, higher UACR and higher serum potassium. No differences were identified between finerenone and placebo with regard to these risk factors.

I have potential conflict of interest to disclose.
AKS reports consultant fees from Bayer, Chinook, GSK, Nephrology Times, and Zydus. SDA has received research support from Abbott Vascular and Vifor Pharma, and personal fees from Abbott Vascular, Bayer, Boehringer Ingelheim, BRAHMS, Cardiac Dimensions, Impulse Dynamics, Novartis, Servier, and Vifor Pharma. BP reports consultant fees from Ardelyx, AstraZeneca, Bayer, Boehringer Ingelheim, Brainstorm Medical, Cereno Scientific, G3 Pharmaceuticals, KBP BioSciences, PhaseBio, Sanofi/Lexicon, Sarfez Pharmaceuticals, scPharmaceuticals, SQ Innovation, Tricida, and Vifor Pharma/Relypsa. He has stock options in Ardelyx, Brainstorm Medical, Cereno Scientific, G3 Pharmaceuticals, KBP BioSciences, Sarfez Pharmaceuticals, scPharmaceuticals, SQ Innovation, Tricida, and Vifor Pharma/Relypsa. He also holds a patent for site-specific delivery of eplerenone to the myocardium (US patent #9931412) and a provisional patent for histone acetylation–modulating agents for the treatment and prevention of organ injury (provisional US patent 63/045,784). PR reports personal fees from Bayer during the conduct of the study. He has received research support and personal fees from AstraZeneca, Bayer, and Novo Nordisk, and personal fees from Astellas Pharma, Abbott, Boehringer Ingelheim, Eli Lilly, Gilead, Mundipharma, Novartis, Sanofi, and Vifor Pharma; all fees are given to Steno Diabetes Center Copenhagen. LMR reports consultant fees from Bayer. YMKF was a full-time employee at Bayer U.S. LLC at the time of data analysis. He is now a full-time employee of Alexion AstraZeneca Rare Disease Unit. CA, MB and KR are full time employees of Bayer AG. ML is an external employee of Bayer AG. GF reports lecture fees and/or that he is a committee member of trials and registries sponsored by Amgen, Bayer, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor Pharma. He is a senior consulting editor for JACC Heart Failure and has received research support from the European Union.

I did not use generative AI and AI-assisted technologies in the writing process.