Optimizing choice of oral interferon-free treatment for genotype 1 hepatitis C virus using testing for NS5A resistance: a cost-utility analysis from the perspective of the Italian National Health Service

Figures & data

Table 3 Annual transition probabilities

From	To	Value
F3	F4	0.051^Citation18,a
F4	DCC	0.042^Citation18,a
	HCC	0.043^Citation18,a
SVR F4	DCC	0.005^Citation19
	HCC	0.008^Citation19
DCC	HCC	0.035^Citation18,a
	Liver transplant	0.023^Citation18,a
	Liver-related death	0.280^Citation18,a
HCC	Liver transplant	0.020^Citation20,Citation21
	Liver-related death	0.509^Citation18,a
Liver transplant	Liver-related death	0.145^Citation18,a
Post liver transplant	Liver-related death	0.053^Citation18,a
All-cause mortality		Age/gender specific^Citation22

Notes:

a Reprinted from Value Health, 14(8), Townsend R, McEwan P, Kim R, Yuan Y, Structural frameworks and key model parameters in cost-effectiveness analyses for current and future treatments of chronic hepatitis C, 1068–1077, Copyright 2011, with permission from Elsevier. doi: 10.1016/j.jval.2011.06.006.¹⁸

Abbreviations: DCC, decompensated cirrhosis; HCC, hepatocellular carcinoma; SVR, sustained virologic response.

Table 1 Baseline characteristics of patient population

Variable	Value	Source
Age (years)	57	Colombo et al^Citation17
Gender (male/female)	67%/33%
Weight (kg)	74
Genotype (1a/1b)	29.1%/70.9%
Baseline fibrosis/cirrhosis
Metavir F3	52.0%	Colombo et al^Citation17
Metavir F4	48.0%
NS5A resistance	13.5%	Sarrazin et al^Citation8,Citation9

Abbreviation: NS5A, nonstructural protein 5A; Metavir F3, severe fibrosis; Metavir F4, compensated cirrhosis.

Table 2 SVR values applied in the model

Population	Treatment	Treatment experienced
		F3 (%)	F4 (%)
NS5A−	SOF + LDV 12/24 weeks	95 (110/116)	100 (113/113)
NS5A+	SOF + LDV 12/24 weeks	65 (11/17)	85 (17/20)
NS5A±*	SMV + SOF 12/24 weeks	95 (38/40)	93 (13/14)

Note:

* NS5A resistance assumed not to impact on SVR with SMV/SOF regimen.^11,13

Abbreviations: LDV, ledipasvir; NS5A, nonstructural protein 5A; SMV, simeprevir; SOF, sofosbuvir; SVR, sustained virologic response.

Table 4 Utilities and costs used in the model

	Cost (€)	Utility
Drug acquisition
SMV/SOF 12/24 weeks	72,000^Citation34
SOF/LDV 12/24 weeks	50,000^Citation34
Health states
SVR F3	299^Citation10*,a	1.00^Citation31,b
SVR F4	405^Citation10,a	1.00^Citation31,b
F3	299^Citation10,a	0.78^Citation31,b
F4	405^Citation10,a	0.78^Citation31,b
DCC	4,473^Citation10,a	0.65^Citation31,b
HCC	5,862^Citation10,a	0.25^Citation31,b
Liver transplant	86,537^Citation10,a	0.50^Citation31,b
Post liver transplant	17,965^Citation10,a	0.70^Citation31,b
On-treatment disutility		−0.03^Citation32

Note:

* Only applied for the year after treatment.

a Marcellusi A, Viti R, Capone A, Mennini F. The economic burden of HCV-induced diseases in Italy. A probabilistic cost of illness model. Eur Rev Med Pharmacol Sci. 2015;19(9):1610–1620.¹⁰

b Petta S, Cabibbo G, Enea M, et al. Cost-effectiveness of sofosbuvirbased triple therapy for untreated patients with genotype 1 chronic hepatitis C. Hepatology. 2014;59(5):1692–1705, with permission from John Wiley and Sons.³¹

Abbreviations: DCC, decompensated cirrhosis; HCC, hepatocellular carcinoma; LDV, ledipasvir; SMV, simeprevir; SOF, sofosbuvir; SVR, sustained virologic response.

Table 5 Discounted base case results for treatment-experienced patients (F3/F4)

	With NS5A testing	No NS5A testing	Increment
Clinical outcomes
Weighted average SVR (%)	96.86	94.22	2.64
Decompensated cirrhosis (%)	6.06	6.73	−0.68
Hepatocellular carcinoma (%)	9.77	10.49	−0.72
Liver Transplantation (%)	0.72	0.79	−0.07
Liver-related death (%)	13.72	14.91	−1.20
HE outcomes (discounted)
Life years	17.104	17.016	0.088
QALYs	16.683	16.519	0.163
Costs (discounted)
Drug costs	€52,970	€50,000	€2,970
Evaluation and monitoring	€1,062	€984	€79
Health state costs	€5,172	€5,431	€−259
Total costs	€59,204	€56,415	€2,789
ICER (cost/QALY)			€17,078

Abbreviations: ICER, incremental cost-effectiveness ratio; NS5A, nonstructural protein 5A; SVR, sustained virologic response; HE, health economic; QALYs, quality adjusted life years

Figure 1 Univariate sensitivity analysis: testing versus no testing.

Abbreviations: DCC, decompensated cirrhosis; HCC, hepatocellular carcinoma; ICER, incremental cost-effectiveness ratio; LDV, ledipasvir; NS5A, nonstructural protein 5A; SMV, simeprevir; SOF, sofosbuvir; SVR, sustained virologic response; TP, transition probability; Util, utility.

Figure 2 Probabilistic sensitivity analysis: two-way cost-effectiveness acceptability curve.

Abbreviations: LDV, ledipasvir; NS5A, nonstructural protein 5A; SMV, simeprevir; SOF, sofosbuvir.

Table 6 Results of scenario analyses

Scenario	Incremental costs (€)	Incremental QALYs	ICER (€/QALY)
Base case	2,789	0.163	17,078
Patients with compensated cirrhosis (Metavir F4) only	2,966	0.087	34,191
Patients with severe fibrosis (Metavir F3) only	2,728	0.182	14,999
Utility for SVR (F3/F4) reduced to 0.90	2,789	0.119	23,370
Drug costs discounted by 40%	1,598	0.163	9,805
Drug costs discounted by 50%	1,302	0.163	7,986
Drug costs discounted by 60%	1,005	0.163	6,168

Abbreviations: ICER, incremental cost-effectiveness ratio; SVR, sustained virologic response.

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