Association of Finerenone Use With Reduction in Treatment-Emergent Pneumonia and COVID-19 Adverse Events Among Patients With Type 2 Diabetes and Chronic Kidney Disease: A FIDELITY Pooled Secondary Analysis

Abstract

Importance: Patients with chronic kidney disease and type 2 diabetes have a higher risk of developing pneumonia as well as an increased risk of severe COVID-19-associated adverse events and mortality. Therefore, the anti-inflammatory effects of mineralocorticoid receptor antagonists via blockade of the mineralocorticoid receptor may alter the risk of pneumonia and COVID-19-associated adverse events in patients with chronic kidney disease and type 2 diabetes.

Objective: To evaluate whether the selective, nonsteroidal mineralocorticoid receptor antagonist finerenone is associated with protection against pneumonia and COVID-19 adverse events in patients with type 2 diabetes and chronic kidney disease.

Design, setting, and participants: This secondary analysis used patient-level data from FIDELITY, a prespecified pooled analysis of 2 multicenter, double-blind, placebo-controlled, event-driven, phase 3 randomized clinical trials: FIDELIO-DKD and FIGARO-DKD, conducted between September 2015 and February 2021. Patients in FIDELIO-DKD or FIGARO-DKD with type 2 diabetes and chronic kidney disease (urine albumin to creatine ratio, 30-5000 mg/g, estimated glomerular filtration rate ≥25 mL/min/1.73 m2) were assessed. Data were analyzed from May 15, 2021, to July 28, 2022.

Exposure: Patients were randomized to finerenone (10 or 20 mg once daily) or matching placebo.

Main outcomes and measures: The main outcomes were investigator-reported incidences of treatment-emergent infective pneumonia adverse events and serious adverse events (during and up to 3 days after treatment) and any COVID-19 adverse events.

Results: Of 13 026 randomized patients (mean [SD] age, 64.8 [9.5] years; 9088 [69.8%] men), 12 999 were included in the FIDELITY safety population (6510 patients receiving finerenone; 6489 patients receiving placebo). Over a median (range) treatment duration of 2.6 (0-5.1) years, finerenone was consistently associated with reduced risk of pneumonia and serious pneumonia vs placebo. Overall, 307 patients (4.7%) treated with finerenone and 434 patients (6.7%) treated with placebo experienced pneumonia (hazard ratio [HR], 0.71; 95% CI, 0.64-0.79; P < .001). Serious pneumonia occurred in 171 patients (2.6%) treated with finerenone and 250 patients (3.9%) treated with placebo (HR, 0.69; 95% CI, 0.60-0.79; P < .001). Incidence proportions of COVID-19 adverse events were 86 patients (1.3%) in the finerenone group and 118 patients (1.8%) in the placebo group (HR, 0.73; 95% CI, 0.60-0.89; P = .002).

Conclusions and relevance: These findings suggest that mineralocorticoid receptor blockade with finerenone was associated with protection against pneumonia and COVID-19 adverse events in patients with type 2 diabetes and chronic kidney disease. Further clinical studies may be warranted.

Trial registration: ClinicalTrials.gov identifiers: FIDELIO-DKD: NCT02540993; FIGARO-DKD: NCT02545049.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Pitt reported receiving personal fees from Bayer, AstraZeneca, Boehringer Ingelheim, Brainstorm Medical, Lexicon, and PhaseBio; personal fees and stock options from KBP Biosciences, Cereno Scientific, scPharmaceuticals, SQ Innovations, G3 Pharmaceuticals, Sarfez, Priton Intel, Tricida, and Vifor Pharma and having patents pending for US 9931412 and US 63045783 outside the submitted work. Dr Agarwal reported receiving personal fees from Akebia Therapeutics, AstraZeneca, Boehringer Ingelheim, Chinook, Eli Lily, Fresenius, Ironwood Pharmaceuticals, Janssen, Lexicon, Merck, Reata, Sanofi; Vertex, Vifor Pharma, and UpToDate; having meals provided by E. R. Squibb & Sons, Opko Pharmaceuticals, and Otsuka America Pharmaceutical; grants from the US Department of Veterans Affairs and National Institutes of Health; serving as a consultant for AbbVie, Akebia Therapeutics, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Celgene, Janssen, and Relypsa; and serving as associate editor for the American Journal of Nephrology and Nephrology Dialysis and Transplantation outside the submitted work. Professor Anker reported receiving personal fees from Bayer, Boehringer Ingelheim, BRAHMS, Cardiac Dimensions, Impulse Dynamics, Novartis, Occlutech, Servier, V-Wave, Vifor Pharma, and Abbott, grants from Vifor Pharma and Abbott, and serving as a consultant for Vifor Pharma and Abbott outside the submitted work. Professor Ruilope reported receiving personal fees from Astellas, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Mundipharma, Sanofi, and Vifor and grants and personal fees from AstraZeneca and Novo Nordisk outside the submitted work. Dr Rossing reported receiving personal fees from AstraZeneca, Boehringer Ingelheim, Astellas, Novo Nordisk, Gilead, Sanofi, and Merck and grants from Novo Nordisk outside the submitted work. Dr Bakris reports receiving grants from Novo Nordisk and Vascular Dynamics, receiving personal fees from Alnylam, Merck, and Relypsa; serving as an editor for the American Journal of Nephrology, Nephrology, and Hypertension, UpToDate, Diabetes Care, and Hypertension Research. Professor Filippatos reported serving in committees for Amgen, Bayer, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor Pharma; serving as an editor for JACC Heart Failure; receiving grants from the European Union; and receiving personal fees from Novartis and Boehringer Ingelheim outside the submitted work. No other disclosures were reported.

Figures

Figure.. Time to Treatment-Emergent Infective Pneumonia

Data are cumulative incidence of Standardized MedDRA Query term infective pneumonia (narrow search) based on Aalen-Johansen estimates in the safety analysis set of the FIDELIO-DKD and FIGARO-DKD trials. AE indicates adverse event; HR, hazard ratio; SAE, serious adverse event.