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.

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.