TY - JOUR
T1 - 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
T2 - A FIDELITY Pooled Secondary Analysis
AU - Pitt, Bertram
AU - Agarwal, Rajiv
AU - Anker, Stefan D
AU - Ruilope, Luis M
AU - Rossing, Peter
AU - Ahlers, Christiane
AU - Brinker, Meike
AU - Joseph, Amer
AU - Lambelet, Marc
AU - Lawatscheck, Robert
AU - Filippatos, Gerasimos S
AU - FIDELIO-DKD and FIGARO-DKD Investigators
PY - 2022/10/3
Y1 - 2022/10/3
N2 - 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.
AB - 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.
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Albumins/therapeutic use
KW - Anti-Inflammatory Agents/therapeutic use
KW - COVID-19
KW - Creatine/therapeutic use
KW - Diabetes Mellitus, Type 2/complications
KW - Diabetic Nephropathies/epidemiology
KW - Mineralocorticoid Receptor Antagonists/therapeutic use
KW - Receptors, Mineralocorticoid/therapeutic use
KW - Renal Insufficiency, Chronic/complications
UR - http://www.scopus.com/inward/record.url?scp=85140856554&partnerID=8YFLogxK
U2 - 10.1001/jamanetworkopen.2022.36123
DO - 10.1001/jamanetworkopen.2022.36123
M3 - Journal article
C2 - 36287567
SN - 2574-3805
VL - 5
SP - e2236123
JO - JAMA network open
JF - JAMA network open
IS - 10
ER -