Cost-effectiveness of empagliflozin as add-on to standard of care for chronic kidney disease management in the United Kingdom

Figures & data

Table 1. Projected changes in eGFR and uACR values over 1 year in patients receiving empagliflozin as add on to SoC and SoC alone.

KDIGO classification	Empagliflozin 10 mg OD plus SoC			Placebo plus SoC
	A1	A2	A3	A1	A2	A3
	Mean (95% CI) change in eGFR (mL/min/1.73 m^2)
G2	NA	–2.2 (–3.26, −1.14)	−3.39 (–3.96, −2.81)	NA	−2.76 (–3.92, −1.59)	−5.14 (–5.7, −4.58)
G3a	NA	−1.60 (–2.32, −0.89)	−3.45 (–3.91, −2.98)	NA	−2.29 (–3.04, −1.55)	−4.66 (–5.14, −4.19)
G3b	−0.58 (–0.96, −0.19)	−1.041 (–1.40, −0.67)	−2.90 (–3.20, −2.60)	−0.83 (–1.2, −0.46)	−1.56 (–1.92, −1.20)	−4.11 (–4.42, −3.80)
G4	−0.32 (–0.87, 0.22)	−0.62 (–1.04, −0.19)	−2.76 (–3.08, −2.45)	−0.15 (–0.71, 0.40)	−0.85 (–1.27, −0.43)	−3.76 (–4.09, −3.44)
All	−1.96 (–2.11, −1.82)			−2.68 (–2.82, −2.53)
	Mean (95% CI) change in uACR
G2	NA	1.26 (0.93, 1.70)	0.67 (0.56, 0.79)	NA	0.93 (0.67, 1.29)	0.75 (0.63, 0.89)
G3a	NA	0.87 (0.71, 1.06)	0.53 (0.46, 0.61)	NA	0.99 (0.80, 1.23)	0.71 (0.62, 0.81)
G3b	1.62 (1.44, 1.82)	0.84 (0.76, 0.94)	0.62 (0.56, 0.67)	1.65 (1.47, 1.85)	1.09 (0.98, 1.22)	0.81 (0.74, 0.88)
G4	2.08 (1.76, 2.44)	1.03 (0.91, 1.18)	0.68 (0.62, 0.74)	2.44 (2.07, 2.87)	1.51 (1.33, 1.71)	0.95 (0.86, 1.04)
All	0.86 (0.83, 0.90)			1.08 (1.04, 1.13)

Abbreviations: CI, confidence interval; eGFR, estimated glomerular filtration rate; NA, not available; OD, once daily; SoC, standard of care; uACR, urine albumin-to-creatinine ratio.

Table 2. Incremental effects of empagliflozin and placebo on other risk factors across health states.*^,†

Risk factor	Empagliflozin 10 mg OD plus SoC	Placebo plus SoC
HbA1c, mmol/mol	−0.5585 (–0.8253, −0.2917)	−0.1455 (–0.4142, 0.1232)
Weight, kg	−1.5525 (–1.7375, −1.3676)	−0.679 (–0.8648, −0.4933)
BMI (calculated), kg/m²	−0.55	−0.24
SBP (mmHg)	−3.915 (–4.3245, −3.5056)	−1.2913 (–1.7019, −0.8808)

* The impact on lipids was not reported.

^† Impact on serum hemoglobin was not programmed into the model as it is not a driver of any of the risk equations in the model.

Abbreviations: BMI, body mass index; HbA1c, glycated hemoglobin; OD, once daily; SBP, systolic blood pressure; SoC, standard of care.

Table 3. Base case model settings.

Model parameter	Option selected
Key model parameters
Time horizon (years)	50 (lifetime)
Number of patients	1,000
Number of iterations (PSA)	500 iterations of 1,000 patients
Discounting rate – effects	3.5%
Discounting rate – costs	3.5%
Half cycle correction	Yes
Cost approach	Option 1: Includes 1st and follow-up years
Utility approach	Option 1: Health state utilities plus disutilities per event/complication
Population baseline risk factors
Patient population	Option 1 – EMPA-KIDNEY full population
eGFR	Distribution over eGFR classes according to EMPA-KIDNEY
eGFR midpoints	As per EMPA-KIDNEY
uACR	Distribution over uACR classes according to EMPA-KIDNEY
uACR midpoints	As per EMPA-KIDNEY
Treatment effect options
Comparators	Empagliflozin + SoC vs SoC alone
eGFR	Annual eGFR change per KDIGO
uACR	Annual uACR change per KDIGO
Adverse events	Rate per 100-patient year
Discontinuation	Rate per 100-patient year
HHF	Hazard ratio vs SoC
Acute kidney injury	Hazard ratio vs SoC
All-cause hospitalization	Unadjusted rate per 100 person-years
Duration of treatment (max)	50 years
Risk factor progression/disease progression after treatment discontinuation
eGFR progression	Fixed changes per eGFR and uACR classes^11 (Grams 2021; Supplementary Table S3)
uACR progression	Lognormal distribution uACR fold^14 (Coresh 2019; Figure 1)
Engine options
Risk of death	Three mutually exclusive causes of death were modeled: CVD death with CKD patch^21 (Matsushita 2020; Web Table 13) plus non-specific cause death (UK National life tables; excluding mortality from CVD and renal causes as per death counts statistics) plus renal death during KRT (UK Renal Registry, Annual Report 2022; Table 2.8)
Risk prediction of CVD mortality	CKD patch, low-risk countries^21 (Matsushita 2020; Web Table 13)
Risk of KRT	Tangri risk equations, 5 years, pooled with six variables (selected because DM is a parameter in the equation)^22 (Tangri 2016; eAppendix 2)
Risk of KRT is applied when eGFR is equal to or below	15 mL/min/1.73 m^2
Age threshold after which KT is not performed	80 years
When in conservative therapy which cost to apply? (ESKD health state costs and/or conservative therapy costs)	Conservative therapy cost only
Risk prediction of CVD	^21(Matsushita 2020; Web Table 13)

Abbreviations: CVD, cardiovascular disease; DM, diabetes mellitus; eGFR: estimated glomerular filtration rate; ESKD, end-stage kidney disease; HHF, hospitalization for heart failure; KDIGO, Kidney Disease Improving Global Outcomes; KRT, kidney replacement therapy; KT, kidney transplantation; PSA, probabilistic sensitivity analysis; SoC, standard of care; uACR, urine albumin-to-creatinine ratio.

Table 4. Base case cost-effectiveness analysis over a lifetime (50 years).

	Overall population			Patients with T2DM			Patients without T2DM
	Empagliflozin 10 mg OD plus SoC	SoC	Incremental	Empagliflozin 10 mg OD plus SoC	SoC	Incremental	Empagliflozin 10 mg OD plus SoC	SoC	Incremental
Total discounted costs (£)	89,911	95,930	−6,019	80,264	81,792	−1,528	90,447	98,510	−8,063
Total discounted LYs	9.59	8.55	1.04	8.73	7.63	1.099	10.35	9.33	1.017
Total discounted QALYs	7.12	6.28	0.84	6.29	5.36	0.925	7.53	6.61	0.921
ICER (£/QALY)	–	–	Dominant	–	–	Dominant	–	–	Dominant
INMB (£) at £20,000/QALY	22,849	–	Cost-effective at £20,000/QALY	20,036	–	Cost-effective at £20,000/QALY	26,473	–	Cost-effective at £20,000/QALY
INMB (QALYs) at £20,000/QALY	1.14	–	–	1.00	–	–	1.32	–	–

Abbreviations: ICER, incremental cost-effectiveness ratio; iNHB, incremental net health benefit; INMB, incremental net monetary benefit; LY, life years; OD, once daily; QALY, quality-adjusted life year; SoC, standard of care; T2DM, type 2 diabetes mellitus.

Table 5. Scenario analyses: Incremental cost-effectiveness ratio and net monetary benefit for empagliflozin in addition to SoC compared to SoC alone.

Scenario	ICER (£/QALY)	NMB (£)*	Change (%) relative to base-case NMB
Base case	Dominant	22,849	–
Major et al. risk equation to predict risk of KRT	Dominant	22,573	−1.21
EMPA-KIDNEY derived trial utilities to predict QALYs	Dominant	24,596	7.64
All-cause hospitalizations	Dominant	22,020	−3.63
eGFR threshold at 20 mL/min/1.73 m^2 to estimate the risk of KRT	Dominant	20,218	−11.51
Annual discount rate 2% (costs; health effects)	Dominant	25,707	+12.51
Annual discount rate 5% (costs; health effects)	Dominant	20,385	−10.78

* At a willingness-to-pay threshold of £20,000.

Abbreviations: eGFR, estimated glomerular filtration rate; ICER, incremental cost-effectiveness ratio; KRT, kidney replacement therapy; NMB, net monetary benefit; QALY, quality-adjusted life year; SoC, standard of care.

Figure 1. Deterministic univariate sensitivity analysis: tornado diagram of the 20 parameters with most impact on net monetary benefit, when comparing empagliflozin in addition to SoC against SoC alone.

Abbreviations: eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; HD, hemodialysis; HS, health state; ITT, intention to treat; KRT, kidney replacement therapy; PD, peritoneal dialysis; RFP, risk factor progression, RRT, renal replacement therapy; SoC, standard of care; uACR, urine albumin-creatinine ratio.

Figure 2. Probabilistic sensitivity analysis: cost-effectiveness plane (A) and acceptability curve (B), for empagliflozin in addition to SoC.

Abbreviations: BC, base case; PSA, probabilistic sensitivity analysis; QALY, quality-adjusted life years; SoC, standard of care.

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Data sharing statement

The data underlying this article will be shared upon reasonable request to the corresponding author.