In recent years, real-world data have been increasingly used to enrich data from interventional studies on treatment effectiveness. To explore the viability of hybrid study designs in pediatric chronic kidney disease (CKD), we assessed the feasibility of identifying a real-world cohort of children with CKD and severely increased proteinuria who satisfied adapted eligibility criteria from the FIONA trial. We used data from the Optum® de-identified Electronic Health Record dataset (Optum® EHR) to identify and characterize children with CKD and severely increased proteinuria in records from January 2013 to December 2022. Patients were identified based on two sets of estimated glomerular filtration rate (eGFR)/serum creatinine and urine protein-to-creatinine ratio (UPCR) measures within a 90- to 365-day period (final date = index). Patients were required to satisfy adapted eligibility criteria from the FIONA trial and have a baseline prescription for angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARBs). Patients were stratified by eGFR and UPCR. Patient characteristics, comorbidities, and medications were descriptively reported. We identified a total of 381 children with CKD and severely increased proteinuria (median age: 14 years; 52.6

Introduction: The FIDELITY pooled analysis of the FIDELIO-DKD and FIGARO-DKD trials showed a complementary benefit of finerenone and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2D). This study used US electronic health record (EHR) data to create an external control arm (ECA) to augment the FIDELITY comparator group and improve the precision of finerenone's treatment effect estimates. Methods: We identified eligible patients from EHR data who met the adapted FIDELITY criteria. These ECA patients were matched (1:1) to the pool of SGLT-2i users within the FIDELITY population using a linear programming method based on baseline demographics and clinical characteristics. We then calculated the treatment effects of finerenone on cardiovascular (CV) and kidney composite end points, hospitalization for heart failure (HHF), and all-cause mortality, incorporating the augmented ECA data. Results: Eligible ECA patients (n = 877) were matched to FIDELITY SGLT-2i users (n = 877), yielding a median (Q1-Q3) absolute standardized mean difference (ASMD) of 0.000 (0.000-0.004). ECA augmentation improved the precision of the trial estimates; data resembled the original FIDELITY estimates but with narrower 95% confidence interval (CI) ranges. For the CV end point and HHF, a significant benefit for finerenone + the SGLT-2i subgroup versus the augmented SGLT-2i controls was observed. Conclusion: Our findings demonstrate that an ECA can effectively augment underrepresented study populations in cardiorenal trials, enhancing the statistical precision of treatment effect estimates when there is sufficient homogeneity between the internal and external control groups.

Novel therapies are emerging for the prevention of chronic kidney disease (CKD) progression in patients with type 2 diabetes (T2D). Within the FOUNTAIN platform (NCT05526157; EUPAS48148), this real-world study aimed to characterize cohorts of adults with CKD and T2D starting therapy with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in Europe, Japan, and the United States (US) during 2012–2021. This multinational, multicohort study was conducted in five data sources: the Danish National Health Registers (DNHR) (Denmark), PHARMO Data Network (PHARMO) (The Netherlands), Valencia Health System Integrated Database (VID) (Spain), Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex) (Japan), and Optum’s de-identified Clinformatics® Data Mart Database (CDM) (US). Eligible patients had T2D (defined by data source-specific algorithms) and CKD (based on diagnosis codes, estimated glomerular filtration rate values, and/or urine albumin-to-creatinine ratio) and initiated an GLP-1 RA during 2012–2021. Baseline demographic, lifestyle, and clinical characteristics were analyzed, and treatment patterns were described. Study cohorts included 18,929 GLP-1 RA initiators in DNHR; 476 in PHARMO; 11,798 in VID; 329 in J-CKD-DB-Ex; and 70,158 in CDM. Across cohorts, mean age ranged from 66.1 years in J-CKD-DB-Ex to 67.9 years in CDM, and between 46.6

Introduction. In 2021, finerenone – a novel, selective non-steroidal mineralocorticoid receptor antagonist – was approved in the US to treat adults with CKD and T2D This study aimed to describe characteristics and short-term outcomes of patients prescribed finerenone since regulatory approval. Methods. This was a retrospective cohort study using claims and electronic health records data from the OM1 Real-World Data Cloud™. A total of 15,948 US adults with a previous diagnosis of chronic kidney disease (CKD) and type 2 diabetes who initiated 10mg or 20mg finerenone between July 2021 and August 2023 were included. Dosing was evaluated at baseline and over up to 12-months’ follow-up. Change from baseline in urine albumin-to-creatinine ratio (UACR) was evaluated at 4 and 12 months (among 913 and 443 patients, respectively, with available repeat UACR values). Hyperkalemia occurrence was determined at 12 months and over total follow-up. Results. Median follow-up was 7.2 months. Mean age was 70.3 years; 44.1% were female. At baseline (-365; 0 days) 70% had CKD stage 3; for patients with UACR measurements 80.8% had moderate/severe albuminuria (≥30mg/g). Median UACR was 203mg/g. Co-medication use was: ACE inhibitors/ARBs (51%), SGLT2is (38%), and GLP-1 RAs (26%). 86% of patients initiated 10mg finerenone, and among 2212 patients still under observation at 12 months, 70% were on 10mg. For finerenone initiators with available UACR data, UACR was reduced by 33% at 4 months and 38% at 12 months. Hyperkalemia occurred in 1.2% of the cohort by 12 months (incidence 2.0 per 100 person-years). Conclusion. Patients who initiated finerenone had a notable reduction in median UACR at 4 months, sustained at 12 months; hyperkalemia occurrence appeared to be low. These initial findings from US clinical practice should be complemented by results from other real-world cohorts of patients started on finerenone.

BACKGROUND Anemia is common in patients with chronic kidney disease and type 2 diabetes. Finerenone improved heart and kidney outcomes in patients with chronic kidney disease and type 2 diabetes in FIDELITY. OBJECTIVES This post hoc analysis investigated the efficacy and safety of finerenone vs placebo by baseline anemia status. METHODS Anemia was defined as serum hemoglobin levels <13 g/dL (male) or <12 g/dL (female) or treatment with an erythropoiesis-stimulating agent at baseline. Outcomes included cardiovascular (CV) and kidney composites, hospitalization for heart failure, and all-cause mortality. Safety was assessed through treatment-emergent adverse events. RESULTS Of 12,971 patients, 33% had anemia at baseline. Finerenone reduced the risk of the CV composite outcome to a greater extent in patients with vs without anemia (HR: 0.75 [95% CI: 0.65-0.88] vs HR: 0.93 [95% CI: 0.82-1.05]; P for interaction = 0.03). Finerenone reduced the risk of the kidney composite outcome vs placebo, with no heterogeneity between patients with vs without anemia (HR: 0.79 [95% CI: 0.65-0.95] and HR: 0.74 [95% CI: 0.60-0.91]; P for interaction = 0.77). The risk of hospitalization for heart failure and all-cause mortality was lower with finerenone vs placebo, irrespective of anemia status. Patients with anemia experienced higher incidence of treatment-emergent hyperkalemia vs those without. CONCLUSIONS Finerenone demonstrated CV and kidney benefit in patients with and without anemia. The benefit of finerenone on CV outcomes was greater in patients with vs without anemia at baseline. Anemia is likely a marker for higher-risk patients who are more susceptible to the benefits of finerenone. (Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease [FIDELIO-DKD], NCT02540993; Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease [FIGARO-DKD], NCT02545049) (JACC Adv. 2025;4:101524) (c) 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

People with chronic kidney disease (CKD) and type 2 diabetes (T2D) have an increased risk of kidney failure and cardiovascular disease. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) have shown cardiorenal protective effects. The objective of this multinational, multidatabase study was to describe the incidence of kidney and cardiovascular outcomes in separate, non–mutually exclusive cohorts of patients with CKD and T2D who initiated either an SGLT2i or a GLP-1 RA. Data describing adults (≥ 18 years) with T2D and CKD who were new users of either SGLT2i or GLP-1 RA from 2012 to 2019 were assessed from population-based Danish National Health Registers (DNHR) and Valencia Health System Integrated Database (VID), hospital-based Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex), and US Optum® de-identified Electronic Health Record dataset (Optum® EHR). Crude incidence rates (IRs) and 95

Objectives This study aimed to evaluate the efficacy and safety of finerenone, a selective, non-steroidal mineralocorticoid receptor antagonist, on cardiovascular and kidney outcomes by age and/or sex. Design FIDELITY post hoc analysis; median follow-up of 3 years. Setting FIDELITY: a prespecified analysis of the FIDELIO-DKD and FIGARO-DKD trials. Participants Adults with type 2 diabetes and chronic kidney disease receiving optimised renin–angiotensin system inhibitors (N=13 026). Interventions Randomised 1:1; finerenone or placebo. Primary and secondary outcome measures Cardiovascular (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalisation for heart failure (HHF)) and kidney (kidney failure, sustained ≥57% estimated glomerular filtration rate (eGFR) decline or renal death) composite outcomes. Results Mean age was 64.8 years; 45.2%, 40.1% and 14.7% were aged <65, 65–74 and ≥75 years, respectively; 69.8% were male. Cardiovascular benefits of finerenone versus placebo were consistent across age (HR 0.94 (95% CI 0.81 to 1.10) (<65 years), HR 0.84 (95% CI 0.73 to 0.98) (65–74 years), HR 0.80 (95% CI 0.65 to 0.99) (≥75 years); P interaction =0.42) and sex categories (HR 0.86 (95% CI 0.77 to 0.96) (male), HR 0.89 (95% CI 0.35 to 2.27) (premenopausal female), HR 0.87 (95% CI 0.73 to 1.05) (postmenopausal female); P interaction =0.99). Effects on HHF reduction were not modified by age (P interaction =0.70) but appeared more pronounced in males (P interaction =0.02). Kidney events were reduced with finerenone versus placebo in age groups <65 and 65–74 but not ≥75; no heterogeneity in treatment effect was observed (P interaction =0.51). In sex subgroups, finerenone consistently reduced kidney events (P interaction =0.85). Finerenone reduced albuminuria and eGFR decline regardless of age and sex. Hyperkalaemia increased with finerenone, but discontinuation rates were <3% across subgroups. Gynaecomastia in males was uncommon across age subgroups and identical between treatment groups. Conclusions Finerenone improved cardiovascular and kidney composite outcomes with no significant heterogeneity between age and sex subgroups; however, the effect on HHF appeared more pronounced in males. Finerenone demonstrated a similar safety profile across age and sex subgroups. Trial registration numbers NCT02540993 , NCT02545049 .

Abstract Background and Aims The Chronic Kidney Disease Prognosis Consortium (CKD-PC) recently developed risk models to predict the 3-year risk of a ≥40% decrease in estimated glomerular filtration rate (eGFR) or to predict kidney failure in the general population. Unlike the kidney failure risk equation, the CKD-PC model is valid for all levels of eGFR (above and below 60 mL/min/1.73 m2) and includes chronic kidney disease (CKD) progression risk factors besides age, sex, eGFR and albuminuria; namely: systolic blood pressure, antihypertensive medication use, history of heart failure, coronary heart disease, atrial fibrillation, smoking status, body mass index, glycated hemoglobin, insulin use, and oral diabetes medication use [1]. We evaluated whether the CKD-PC model, developed using electronic health record data, is valid for use in a contemporary clinical population using the FIDELITY pooled dataset from international randomized clinical trials of finerenone [2]. Additionally, to inform clinical practice, we evaluated the efficacy of finerenone using categories of 3-year CKD progression risk as predicted by the model. Method FIDELITY was an individual, patient-level, prespecified, pooled efficacy and safety analysis of the phase III FIDELIO-DKD and FIGARO-DKD trials of patients with CKD and type 2 diabetes (T2D), randomized 1:1 to finerenone or placebo. The 3-year CKD progression risk of these patients was predicted and the validity of the CKD-PC model was evaluated using area under the curve (AUC) score (with higher scores indicating better risk prediction), Brier score (lower scores indicating better prediction), and by calibration plots of observed versus predicted risk by deciles of 3-year CKD progression risk. To evaluate the efficacy of finerenone, 3-year risk was categorized in quartiles and the effect of finerenone versus placebo on a kidney composite outcome, defined as kidney failure, a sustained ≥40% decrease in eGFR from baseline over ≥4 weeks, or renal death, was assessed. Results The FIDELITY population comprised 13,026 individuals with a mean eGFR of 58 mL/min/1.73 m2 and urine albumin-to-creatinine ratio of 515 mg/g. The median follow-up was 3 years and there were 1849 total kidney outcome events. Of 12,968 patients analyzed, the median 3-year risk of kidney failure was 15% (Q1–Q3: 9–24%). Overall, the model demonstrated good discrimination to predict a ≥40% kidney composite outcome for patients with CKD and T2D in FIDELITY: AUC score 0.726 (95% confidence interval [CI] 0.712–0.739) and Brier score 0.100 (95% CI 0.097–0.103). The predicted 3-year risk was generally slightly higher than the observed risk (Fig. 1). Finerenone was effective in preventing CKD progression across the risk quartiles (p-interaction = 0.094) with a trend towards greater efficacy in the higher risk quartiles (3-year risk of CKD progression ≥10%) (Fig. 2). All risk groups showed benefit with finerenone compared to placebo regarding eGFR decline in the chronic phase. Conclusion The CKD-PC risk model for CKD progression performed well in a large global clinical trial population of patients with CKD and T2D. Finerenone was effective across the range of baseline risk of CKD progression.

The clinical landscape for the treatment of patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) is rapidly evolving. As part of the FOUNTAIN platform (NCT05526157; EUPAS48148), we described and compared cohorts of adult patients with CKD and T2D initiating a sodium-glucose cotransporter 2 inhibitor (SGLT2i) before the launch of finerenone in Europe, Japan, and the United States (US). This was a multinational, multi-cohort study of patients with T2D in five data sources: the Danish National Health Registers (DNHR) (Denmark), PHARMO Data Network (The Netherlands), Valencia Health System Integrated Database (VID) (Spain), Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex) (Japan), and Optum’s de-identified Clinformatics® Data Mart Database (CDM) (US). Eligible patients had CKD (based on either diagnosis codes, eGFR values, and/or urine ACR) and initiated an SGLT2i between 2012 and 2021. Baseline demographic, lifestyle, and clinical characteristics were analyzed, and drug utilization patterns were described. The final cohorts included 21,739 patients in DNHR, 381 in PHARMO, 31,785 in VID, 1157 in J-CKD-DB-Ex, and 56,219 in CDM. Across data sources, approximately 41–70

Background: Chronic kidney disease (CKD) affects >800 million individuals worldwide and is often underrecognized. Early detection, identification and treatment can delay disease progression. Klinrisk is a proprietary CKD progression risk prediction model based on common laboratory data to predict CKD progression. We aimed to externally validate the Klinrisk model for prediction of CKD progression in FIDELITY (a prespecified pooled analysis of two finerenone phase III trials in patients with CKD and type 2 diabetes). In addition, we sought to identify evidence of an interaction between treatment and risk. Methods: The validation cohort included all participants in FIDELITY up to 4 years. The primary and secondary composite outcomes included a >= 40% decrease in estimated glomerular filtration rate (eGFR) or kidney failure, and a >= 57% decrease in eGFR or kidney failure. Prediction discrimination was calculated using area under the receiver operating characteristic curve (AUC). Calibration plots were calculated by decile comparing observed with predicted risk. Results: At time horizons of 2 and 4 years, 993 and 1795 patients experienced a primary outcome event, respectively. The model predicted the primary outcome accurately with an AUC of 0.81 for 2 years and 0.86 for 4 years. Calibration was appropriate at both 2 and 4 years, with Brier scores of 0.067 and 0.115, respectively. No evidence of interaction between treatment and risk was identified for the primary composite outcome (P = .31). Conclusions: Our findings demonstrate the accuracy and utility of a laboratory-based prediction model for early identification of patients at the highest risk of CKD progression.

AbstractAimsLeft ventricular hypertrophy (LVH) has been associated with an increased risk of cardiovascular (CV) disease and linked to increased morbidity and mortality. In patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), hypertension is common, and patients with these co‐morbidities additionally have a high prevalence of LVH. This analysis of the prespecified pooled FIDELITY analysis comprising the randomized, double‐blind, placebo‐controlled, multicentre FIDELIO‐DKD and FIGARO‐DKD phase III studies aimed to explore the CV and kidney effects of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, in patients with CKD and T2D stratified by a diagnosis of LVH at baseline.Methods and resultsA diagnosis of LVH in the FIDELITY patient population was determined at baseline using investigator‐reported electrocardiogram (ECG) findings. The two efficacy outcomes, assessed by baseline LVH, were the composite CV outcome of time to CV death, non‐fatal myocardial infarction, non‐fatal stroke, or hospitalization for heart failure (HHF), and a composite kidney outcome of time to onset of kidney failure, a sustained decrease in estimated glomerular filtration rate (eGFR) ≥57% from baseline over ≥4 weeks, or kidney‐related death. Safety outcomes by baseline LVH were reported as treatment‐emergent adverse events. At baseline out of 13 026 patients in FIDELITY, 96.5% had hypertension and 9.6% had investigator‐reported LVH. The relative risk reduction for the composite CV and kidney outcomes with finerenone versus placebo was lower in the LVH subgroup; however, the treatment effect of finerenone was not modified by baseline LVH for either outcome (Pinteraction = 0.1075 for composite CV outcome and Pinteraction = 0.1782 for composite kidney outcome). Analysis of the composite CV outcome components showed a greater reduction in the risk of HHF versus placebo for patients with baseline LVH compared with those without (Pinteraction = 0.0024). Overall safety events were comparable between the LVH subgroups and treatment arms. Treatment‐emergent hyperkalaemia was observed more frequently with finerenone versus placebo, but discontinuation rates were low in both treatment arms and between LVH subgroups.ConclusionsIn conclusion, the overall CV and kidney benefits of finerenone versus placebo were not modified by the presence of LVH at baseline, with overall safety findings being similar between LVH subgroups. A greater benefit was observed for HHF in patients with versus without LVH, suggesting that LVH may be a predictor of the treatment effect of finerenone on HHF.

Abstract Background and Aims Evidence from clinical trials demonstrates that finerenone reduces the risk of cardiovascular and renal complications among patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). What is lacking is the evidence on finerenone use in real-world clinical practice. Method The present analysis is based on a longitudinal single-arm cohort study of patients initiating finerenone between July 2021 and August of 2023 and with prior diagnoses of CKD and T2D. Data were obtained from US electronic health records and insurance claims (OM1 Real-World Data CloudTM). CKD was defined as either having 1 diagnostic code for CKD stage 2-4 or unspecified stage, two estimated glomerular filtration rate (eGFR) measurements between 15 and 60 ml/min/1.73 m2, or two urine albumin to creatinine ratio (UACR) measurements over 30 mg/g; T2D was defined as having a diagnostic code for T2D. We described patient demographics, comorbidities, and comedications at baseline (365 days prior and including index date), and incidence rates of cardiovascular and renal outcomes, including eGFR and UACR changes over time. The presented analysis (NCT05703880) is part of the multi-national, multi-database observational research platform FOUNTAIN. Results We identified 28,056 new users of finerenone with prior CKD and T2D. The users had a mean (SD) age of 68.8 (10.8) years and 44.8% were female. Comorbidities of interest at baseline were hypertension (89.8%), cardiovascular disease (21.2%), neuropathy (13.4%), retinopathy (8.1%), heart failure (7.9%), and cerebrovascular disease (4.2%). Assessment of comedication use at baseline indicates that patients who initiate finerenone had exposure to renin–angiotensin system inhibitors (52.5%), sodium-glucose cotransporter-2 inhibitors (39.2%), or glucagon-like peptide-1 receptor agonists (27.4%) within 180 days prior to initiating finerenone. Overall, 82.5% of patients initiated finerenone at 10 mg/d, while 17.5% of patients started with 20 mg/d. Complete results including incidence rates of cardiovascular and renal outcomes, hyperkalemia events, and changes in kidney function measures (eGFR, UACR) during follow-up will be presented as part of the conference presentation. Conclusion Data from patients receiving finerenone as part of clinical practice in the USA suggest that finerenone is used concurrently with other renal and cardiovascular protective medication-classes recommended for patients with CKD and T2D.

BACKGROUND:In patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), finerenone, a nonsteroidal mineralocorticoid receptor antagonist, reduces cardiovascular and kidney failure outcomes. Finerenone also lowers the urine albumin-to-creatinine ratio (UACR). Whether finerenone-induced change in UACR mediates cardiovascular and kidney failure outcomes is unknown.OBJECTIVE:To quantify the proportion of kidney and cardiovascular risk reductions seen over a 4-year period mediated by a change in kidney injury, as measured by the change in log UACR between baseline and month 4.DESIGN:Post hoc mediation analysis using pooled data from 2 phase 3, double-blind trials of finerenone. (ClinicalTrials.gov: NCT02540993 and NCT02545049).SETTING:Several clinical sites in 48 countries.PATIENTS:12 512 patients with CKD and T2D.INTERVENTION:Finerenone and placebo (1:1).MEASUREMENTS:Separate mediation analyses were done for the composite kidney (kidney failure, sustained ≥57% decrease in estimated glomerular filtration rate from baseline [approximately a doubling of serum creatinine], or kidney disease death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) outcomes.RESULTS:At baseline, median UACR was 514 mg/g. A 30% or greater reduction in UACR was seen in 3338 (53.2%) patients in the finerenone group and 1684 (27.0%) patients in the placebo group. Reduction in UACR (analyzed as a continuous variable) mediated 84% and 37% of the treatment effect on the kidney and cardiovascular outcomes, respectively. When change in UACR was analyzed as a binary variable (that is, whether the guideline-recommended 30% reduction threshold was met), the proportions mediated for each outcome were 64% and 26%, respectively.LIMITATION:The current findings are not readily extendable to other drugs.CONCLUSION:In patients with CKD and T2D, early albuminuria reduction accounted for a large proportion of the treatment effect against CKD progression and a modest proportion of the effect against cardiovascular outcomes.PRIMARY FUNDING SOURCE:Bayer AG.

Rationale & Objective: In FIDELITY, finerenone improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). This analysis explored the efficacy and safety of finerenone in Black patients.Study Design: Subanalysis of randomized controlled trials.Setting & Participants: Patients with T2D and CKD.Intervention: Finerenone or placebo.Outcomes: Composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure; composite of kidney failure, sustained >= 57% estimated glomerular filtration rate (eGFR) decline from baseline maintained for >= 4 weeks, or renal death.Results: Of the 13,026 patients, 522 (4.0%) self-identified as Black. Finerenone demonstrated similar effects on the cardiovascular composite outcome in Black (HR, 0.79 [95% CI, 0.51-1.24]) and non-Black patients (HR, 0.87 [95% CI, 0.79-0.96; P = 0.5 for interaction]). Kidney composite outcomes were consistent in Black (HR, 0.71 [95% CI, 0.43-1.16]) and non-Black patients (HR, 0.76 [95% CI, 0.66-0.88; P = 0.9 for interaction]). Finerenone reduced urine albumin-to-creatinine ratio by 40% at month 4 (least-squares mean treatment ratio, 0.60 [95% CI, 0.52-0.69; P < 0.001]) in Black patients and 32% at month 4 (least-squares mean treatment ratio, 0.68 [95% CI, 0.66-0.70; P < 0.001]) in non-Black patients, versus placebo. Chronic eGFR decline (month 4 to end-of-study) was slowed in Black and non-Black patients treated with finerenone versus placebo (between-group difference, 1.4 mL/min/1.73 m(2) per year [95% CI, 0.33-2.44; P = 0.01] and 1.1 mL/min/1.73 m(2) per year [95% CI, 0.89-1.28; P < 0.001], respectively). Safety outcomes were similar between subgroups.Limitations: Small number of Black patients; analysis was not originally powered to determine an interaction effect based on Black race.Conclusions: The efficacy and safety of finerenone appears consistent in Black and non-Black patients with CKD and T2D.

Background Several early-phase clinical trials for the treatment of nonalcoholic steatohepatitis (NASH) use liver fat content as measured with the MRI-derived proton density fat fraction (PDFF) for a primary outcome. These trials have shown relative reductions in liver fat content with placebo treatment alone, a phenomenon termed "the placebo effect." This phenomenon confounds the results and limits generalizability to future trials. Purpose To quantify the effect of placebo treatment on change in the absolute PDFF value and to identify variables associated with this observed change. Materials and Methods This is a secondary analysis of prospectively collected data from seven early phase clinical trials that included participants with a diagnosis of NASH based on MRI and/or liver biopsy who received placebo treatment. The primary outcome was a greater than or equal to 30% relative reduction in PDFF after placebo treatment. Normalization of PDFF, relative change in alanine aminotransferase (ALT) level, and normalization of ALT level were also examined. An exploratory linear mixed-effects model was used to estimate an overall change in absolute PDFF and to explore parameters associated with this response. Results A total of 187 participants (median age, 52 years [IQR, 43-60 years]; 114 women) who received placebo treatment were evaluated. A greater than or equal to 30% relative reduction in baseline PDFF was seen in 20% of participants after 12 weeks of placebo treatment (10 of 49), 9% of participants after 16 weeks (two of 22), and 28% of participants after 24 weeks (34 of 122). A repeated-measures linear mixed-effects model estimated a decrease of 2.3 units (median relative reduction of 13%) in absolute PDFF values after 24 weeks of placebo treatment (95% CI: 3.2, 1.4; P < .001). Conclusion In this analysis of 187 participants, a clinically relevant decrease in PDFF was observed with placebo treatment. Based on the study model, assuming an absolute PDFF decrease of approximately 3 units (upper limit of 95% CI) to account for this "placebo effect" in sample size calculations for future clinical trials is suggested. Clinical trial registration nos. NCT01066364, NCT01766713, NCT01963845, NCT02443116, NCT02546609, NCT02316717, and NCT02442687 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Yoon in this issue.