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.

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.