Cost-effectiveness of add-on empagliflozin versus standard of care in management of CKD in Malaysia, Thailand and Vietnam – findings from a modelling study assessing an EMPA-KIDNEY eligible population, using CKD progression model

Figures & data

Figure 1. Underlying model structure. BMI, body mass index; CKD, chronic kidney disease; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; ESKD, end stage kidney disease; HbA1c, glycated haemoglobin; HF, heart failure; KDIGO, kidney disease: improving global outcomes; PAD, peripheral arterial disease; uACR, urine albumin-creatinine ratio; TIA, transient ischaemic stroke.

Table 1. Annual absolute changes in eGFR based on KDIGO categories used in the model.

Health state	Empagliflozin plus SoC			SoC alone
	A1	A2	A3	A1	A2	A3
G2	NA	−2.2	−3.39	NA	−2.76	−5.14
G3a	NA	−1.6	−3.45	NA	−2.29	−4.66
G3b	−0.58	−1.04	−2.9	−0.83	−1.56	−4.11
G4	−0.32	−0.62	−2.76	−0.15	−0.85	−3.76

Values are absolute changes in eGFR values (in ml/min/1.73m²) based on the KDIGO health state in the previous cycle; NA, not applicable (too few patients analyzed to estimate values).

Table 2. Annual fold change in uACR based on KDIGO categories used in the model.

Health state	Empagliflozin plus SoC			SoC alone
	A1	A2	A3	A1	A2	A3
G2	NA	1.26	0.67	NA	0.93	0.75
G3a	NA	0.87	0.53	NA	0.99	0.71
G3b	1.62	0.84	0.62	1.65	1.09	0.81
G4	2.08	1.03	0.68	2.44	1.51	0.95

Values are relative fold changes in uACR values based on the KDIGO health state in the previous cycle; NA, not applicable (too few patients analyzed to estimate values).

Table 3. Treatment effects on other risk-factors used in the model.

Risk factor	Unit	Empagliflozin plus SoC	SoC alone
HbA1c	mmol/mol	−0.5585	−0.1455
Weight	Kg	−1.5525	−0.679
BMI (calculated)	Kg/m²	−0.55	−0.24
Hb	g/dL	0.6032	−0.1382
SBP	mmHg	−3.915	−1.2913
DBP	mmHg	−1.6391	−1.2226

Table 4. Summary of the cost inputs used in the model.

	Malaysia (MYR)		Thailand (THB)		Vietnam (VND)
	Mean		Mean		Mean
Health state name‡
G1	2,430.82		8,125		42,582,805
G2	3,426.74		9,016		42,582,805
G3a	2,749.32		29,949		42,582,805
G3b	2,912.44		29,949		42,582,805
G4	2,595.49		32,898		60,656,247
G5	12,730.29*		42,551		60,656,247
Event costs
	First year	Follow-on	First year	Follow-on	First year	Follow-on
CVD co-morbidities and complications
Myocardial infarction	22,132.57	2,058.25	110,669	27,717	68,559,258	24,940,526
Unstable angina	12,538.73§	1,513.25§	62,697	20,378	61,055,721§	22,210,885§
Stroke (including TIA)	9,981.30	1,585.48	74,279	24,860	22,931,754	18,160,065
Congestive heart failure (CHF) (chronic)	8,206.97	2,564.93	61,282	26,492	50,089,922	18,221,740
PAD and PVD (driven by smoking, stenting)	24,716.80§	3,893.58§	162,787	52,433	158,524,918§	57,668,285§
End stage renal disease and events
Peritoneal dialysis (PD)	39,005.72		478,937		180,583,763
Haemodialysis (HD)	41,304.53		470,601		180,583,763
Kidney transplant
Kidney transplant (living donor)	105,087.43	29,384	797,735	348,302.74	348,831,248§	127,992,767§
Kidney transplant (deceased donor)	181,316.13		1,049,539		530,403,540
% Of patients getting living donor renal transplant	53%		19%		93%
Anaemia	1,655.11		20,793.24		7,446,516
Acute kidney injury (AKI) – outpatient	402.89		4,345.92		4,121,345§
Acute kidney injury (AKI) – hospitalization	3,886.87		41,927		14,061,333§
Leg amputation	6,805.93		130,437		3,633,308

^‡ Assumed to the be the same irrespective of uACR category (A1–A3)

*Assumed to follow a ratio of the Thai G1:G5 costs to exclude dialysis costs from the monitoring costs.

^§ Estimated values based on similar country estimates.

Table 5. Cost estimation for SoC.

	Usage within EMPA-KIDNEY (%)	Cost per tablet (local currency)			Estimated within class usage for country
Class of drug		MY	TH	VN	MY	TH	VN
ACEi
Ramipril*	41.6	1.2	3.6	4,736	44.5%	63.8%	44.5%
Perindopril	23.6	0.7	9.7	6,056	25.3%	36.2%	25.3%
Lisinopril*	22.1	0.6	n/a	5,691	23.7%	n/a	23.7%
Enalapril	6.0	1.3	n/a	1,200	6.5%	n/a	6.5%
Annual cost (per class)					569.9	2,964.5	3,111,949
ARBs
Losartan	30.0	1.2	1.5	9,420	44.1%	45.4%	46.6%
Candesartan	21.1	n/a	10.3	5,550	n/a	31.9%	32.8%
Irbesartan	15.0	1.6	4.5	n/a	22.1%	22.7%	n/a
Valsartan	13.3	1.2	n/a	9,366	19.5%	n/a	20.6%
Telmisartan	9.8	1.8	n/a	n/a	14.4%	n/a	n/a
Annual Cost (per class)					512.8	1,831.0	2,971,312
Total Cost for SoC					1,082.7	4,795.5	6,083,261
Empagliflozin (10 mg)		3.64	40.45	23,072

* Assumed to require 2 tables per day.

Table 6. 1-Year transition probabilities across KRT modalities or death.

	PD	HD	RT	Death
PD (%)	87.49	0	0.51	12
HD (%)	0	87.77	0.23	12

Table 7. Summary of the cost-utility analysis results.

	Malaysia			Thailand			Vietnam
	Empagliflozin  + SoC	SoC	Incremental	Empagliflozin  + SoC	SoC	Incremental	Empagliflozin  + SoC	SoC	Incremental
Total discounted costs	103,095.24	107,144.25	−4,049.01	1,022,706.17	1,041,036.85	−18,330.68	850,572,228	768,390,471	82,181,757
Total discounted LYs	8.37	7.09	1.282	8.44	7.11	1.327	8.42	7.12	1.306
Total discounted QALYs	6.15	5.11	1.038	6.20	5.13	1.072	6.19	5.13	1.056
Incremental cost per LYs			Dominant			Dominant	62,929,670
Incremental cost per QALYs			Dominant			Dominant	77,838,407		Cost-effective
Breakdown of costs
Time on treatment (years)	5.50	3.93	1.57	5.53	3.92	1.61	5.52	3.93	1.59
Monitoring	30,543.77	30,524.34	19.43	258,970.48	220,996.51	37,973.97	430,757,072	362,383,370	68,373,701
Treatment	11,605.96	3,924.47	7,681.50	94,526.16	17,350.62	77,175.54	70,019,359	22,055,288	47,964,072
Adverse events	49.32	6.42	42.90	945.18	122.95	822.23	26,328	3,425	22,903
Total KRT	33,425.01	48,994.38	−15,569.37	382,553.73	559,284.68	−176,730.95	146,124,213	213,437,165	−67,312,952
CVD Complications	21,054.91	17,753.33	3,301.57	207,153.70	171,092.54	36,061.16	175,898,721	144,922,536	30,976,186
Anaemia	4,964.15	4,538.10	426.05	62,693.61	57,001.42	5,692.18	22,388,196	20,431,491	1,956,704
AKI	1,452.12	1,403.21	48.92	15,863.31	15,188.12	675.19	5,358,339	5,157,196	201,143
Total costs	103,095.24	107,144.25	−4,049.01	1,022,706.17	1,041,036.85	−18,330.68	850,572,228	768,390,471	82,181,757

Table 8. Average risk of CV and renal outcomes for empagliflozin (plus SoC) versus SoC alone over the modelled time horizon.

	Empagliflozin + SoC (%)	SoC (%)	Incremental (%)
1st ASCVD (1st MI and 1st stroke)	16.9	14.1	2.87
1st MI	8.8	7.6	1.20
1st Stroke	2.5	2.2	0.30
1st Unstable angina	9.1	7.7	1.37
1st TIA	1.5	1.3	0.20
HF new onset only	22.7	22.4	0.33
PAD new onset only	9.4	8.0	1.40
ESKD as per KRT pathway
ESKD defined as per initiating KRT	41.37	51.80	−10.43
Peritoneal dialysis	8.10	9.43	−1.33
PD move to HD	1.73	1.37	0.37
PD move to RT	0.00	0.30	−0.30
Fatal PD	4.37	5.57	−1.20
Haemodialysis	35.27	43.70	−8.43
HD move to RT	0.60	0.90	−0.30
HD move to PD	1.33	0.77	0.57
Fatal HD	24.13	30.57	−6.43
Renal transplant (living or deceased donor)	0.70	1.40	−0.70
Failed RT	0.20	0.30	−0.10
RT failed & move to HD	0.00	0.00	0.00
RT failed & move to PD	0.20	0.30	−0.10
Fatal RT	0.00	0.00	0.00
Failed with New RT	0.00	0.00	0.00

Table 9. Model outcomes based on T2DM status.

		Incremental values
		Malaysia	Thailand	Vietnam
With diabetes	Total discounted costs	−2,527.15	−9,110.13	81,115,916.73
	Total discounted LYs	1.158	1.215	1.200
	Total discounted QALYs	0.936	0.978	0.967
	Incremental cost per LYs	Dominant	Dominant	67,578,923.07
	Incremental cost per QALYs	Dominant	Dominant	83,908,286.30
Without diabetes	Total discounted costs	−10,717.32	−78,601.66	54,339,148.10
	Total discounted LYs	1.290	1.297	1.296
	Total discounted QALYs	1.075	1.080	1.080
	Incremental cost per LYs	Dominant	Dominant	41,928,797.82
	Incremental cost per QALYs	Dominant	Dominant	50,311,468.91

Table 10. Model outcomes for patients with normo- or microalbuminuria.

	Incremental values
	Malaysia	Thailand	Vietnam
Total discounted costs	3,274.35	39,433.97	118,694,432.23
Total discounted LYs	1.442	1.498	1.477
Total discounted QALYs	1.144	1.186	1.170
Incremental cost per LYs	846.97	26,319.26	80,366,310.52
Incremental cost per QALYs	1,068.24	33,252.91	101,472,842.82

Figure 2. One-way sensitivity analysis results – Malaysia. The horizontal axis is the Net Monetary Benefit (NMB) in Malaysian Ringgit (MYR); 1 USD = 4.66 MYR. A positive NMB indicates a cost-effective result (considering a willingness-to-pay threshold of MYR 52,689 (USD 11,307))

Figure 3. One-way sensitivity analysis results – Thailand. The horizontal axis is the Net Monetary Benefit (NMB) in Thai Baht (THB); 1 USD = 35.28 THB. A positive NMB indicates a cost-effective result (considering a willingness-to-pay threshold of THB 160,000 (USD 4,535))

Figure 4. One-way sensitivity analysis results – Vietnam. The horizontal axis is the Net Monetary Benefit (NMB) in Vietnamese Dong (VND); 1 USD = 24,224 VND. A positive NMB indicates a cost-effective result (considering a willingness-to-pay threshold of VND 96,890,026 (USD 4,000))

Figure 5. Probabilistic sensitivity analysis plot for Malaysia.

Figure 6. Probabilistic sensitivity analysis plot for Thailand.

Figure 7. Probabilistic sensitivity analysis plot for Vietnam.