Finerenone shields against pneumonia, COVID-19 in diabetic patients with CKD

Patients with concomitant chronic kidney disease (CKD) and type 2 diabetes (T2D) who are undergoing mineralocorticoid receptor blockade with finerenone are better protected against pneumonia and COVID-19, according to a secondary analysis of data from the FIDELITY trials.

“We observed a significant reduction in pneumonia and serious [pneumonia] associated with finerenone compared with placebo, with early onset of the associated protection based on cumulative incidence analyses. There was also a lower risk of COVID-19 among patients who received finerenone,” the investigators said.

The phase III FIDELITY trials— FIDELIO-DKD and FIGARO-DKD—included 13,026 patients (mean age 64.8 years, 69.8 percent men) with T2D and CKD (urine albumin to creatine ratio 30–5,000 mg/g, estimated glomerular filtration rate ≥25 mL/min/1.73 m²). Of these, 12,999 were included in the present analysis (6,510 patients receiving finerenone 10 or 20 mg once daily; 6,489 patients receiving placebo).

Over a median treatment duration of 2.6 years, pneumonia occurred less frequently among finerenone-treated patients than among those treated with placebo (4.7 percent vs 6.7 percent; hazard ratio [HR], 0.71, 95 percent confidence interval [CI], 0.64–0.79; p<0.001). The same was true for serious pneumonia (2.6 percent vs 3.9 percent; HR, 0.69, 95 percent CI, 0.60–0.79; p<0.001). [JAMA Netw Open 2022;5:e2236123]

Most patients with treatment-emergent pneumonia persisted with their medication without dose adjustments, with drug withdrawal occurring in six patients (2.0 percent) in the finerenone group and eight patients (1.8 percent) in the placebo group. More than 90 percent of patients in both groups received concomitant medications for pneumonia, the most common of which were systemic anti-infectives.

With respect to COVID-19, fewer patients in the finerenone vs placebo group contracted the infection (1.3 percent vs 1.8 percent; HR, 0.73, 95 percent CI, 0.60–0.89; p=0.002). There was no between-group difference in terms of the proportion of patients with mild, moderate, or severe COVID-19.

How finerenone may ward off the risks of pneumonia and COVID-19 may involve the modulation of ACE2 expression, as well as anti-inflammatory and antifibrotic mechanisms, the investigators pointed out. [Pharmaceuticals 2021;14:71] 

Such antifibrotic and anti-inflammatory effects have been demonstrated previously. In rodent models of idiopathic pulmonary fibrosis, for example, the drug brought down the concentration of pulmonary proinflammatory and profibrotic markers in lung homogenate, with finerenone being more effective than approved antifibrotic drugs (eg, pirfenidone, nintedanib). [Eur J Pharmacol 2013;718:290-298; Eur Heart J 2021;42:ehab724.2932]

“Therefore, we propose that a combination of factors, including improvements in pulmonary inflammation and fibrosis, coupled with upregulation of ACE2 expression and amelioration of right-heart pressure and pulmonary congestion, are likely to lead to an improved pulmonary environment that is less susceptible to a propagation of pulmonary infection and inflammation,” the investigators said.

“Although no between-group differences were observed in other associated respiratory infections [ie, nasopharyngitis, bronchitis, and influenza], the striking reduction in risk of pneumonia observed in both independent [FIDELITY] studies might suggest that the propagation of pulmonary infection into lobar or bronchial consolidation may be reduced by finerenone,” they added.

These results have important clinical implications, given that patients with CKD and T2D have a higher risk of developing pneumonia as well as an increased risk of severe COVID-19 and mortality, according to the investigators.

“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 this population,” they said.