Cost per care of the first year of direct antiviral agents in the Liguria Region: a multicenter analysis

Figures & data

Table 1 Clinical and demographic features at baseline

Features	All patients, absolute value (%) (N=327)
Demographics
Prescribing center
San Martino – UOS epatologia	114 (34.86)
San Martino – Clinica Malattie Infettive	61 (18.65)
La Spezia – SC Malattie Infettive	57 (17.43)
Genova – Galliera SC Malattie Infettive	47 (14.37)
Sanremo – SC Malattie Infettive	36 (11.01)
Savona – SC Malattie Infettive	12 (3.67)
Resident in Regione Liguria	318 (97.25)
Gender
Male	233 (71.25)
Female	94 (28.75)
Age, years	57.11±9.72
HCV treatment details
Previous treatment	174 (53.21)
Criteria for prescription according to Italian Drugs Agency
1	251 (76.76)
2	1 (0.31)
3	14 (4.28)
4	60 (18.35)
6	1 (0.31)
Genotype
1a	80 (24.46)
1b	94 (28.75)
2	31 (9.48)
3	78 (23.85)
4	44 (13.46)
Fibrosis stage
F1	4 (1.22)
F2	6 (1.83)
F3	64 (19.57)
F4	253 (77.37)
Child Pugh (only for fibrosis stage 4)*
Child A	228 (90.12)
Child B	24 (9.49)
Child C	1 (0.40)
Treatment regimen
SOF+RBV	76 (23.24)
SOF+LDP+RBV	52 (15.90)
SOF+SIM+RBV	51 (15.60)
PTVr/OBV+DSV+RBV	44 (13.46)
SOF+DCV+RBV	36 (11.01)
SOF+SIM	26 (7.95)
SOF+LDP	16 (4.89)
PTVr/OBV+RBV	10 (3.06)
PTVr/OBV+DSV	9 (2.75)
SOF+DCV	7 (2.14)
Length of treatment (weeks)	15.87±5.75
Comorbidities
Patients presenting with at least one comorbidity	168 (51.38)
Number
No comorbidity	159 (48.62)
1 comorbidity	85 (25.99)
2 comorbidities	59 (18.04)
≥3 Comorbidities	24 (7.34)
Comorbidities
Drug abuse	104 (31.80)
HIV infection	74 (22.63)
Heart disease	52 (15.90)
Metabolic syndrome	34 (10.40)
Renal disease	10 (3.06)
HBV infection	3 (0.92)

Notes:

* % Calculated in patients with fibrosis stage F4. Data are presented as: continuous variables: mean±SD; categorical variables: n (%).

Abbreviations: DCV, daclatasvir; DSV, dasabuvir; HCV, hepatitis C virus; HIV, human immunodeficiency virus; LDP, ledipasvir; OBV, ombitasvir; PTVr, ritonavir boosted paritaprevir; RBV, ribavirin; SD, standard deviation; SIM, simeprevir; SOF, sofosbuvir; UOS, Unità Operativa Semplice; SC, Struttura Complessa; HBV, hepatitis B chronic infection.

Table 2 SVR rate according to genotype and regimen prescribed

Regimen anti-HCV prescribed	Genotype 1	Genotype 1a	Genotype 1b	Genotype 2	Genotype 3	Genotype 4	Total
	n/N (%)	n/N (%)	n/N (%)	n/N (%)	n/N (%)	n/N (%)	n/N (%)
SOF+RBV				30/31 (96.77)	37/45 (82.22)		67/76 (88.16)
SOF+LDP+RBV	43/45 (95.56)	30/32 (93.75)	13/13 (100.00)			7/7 (100.00)	50/52 (96.15)
SOF+SIM+RBV	35/38 (92.11)	15/16 (93.75)	20/22 (90.91)			12/13 (92.31)	47/51 (92.16)
PTVr/OBV+DSV+RBV	42/44 (95.45)	13/14 (92.86)	29/30 (96.67)				42/44 (95.45)
SOF+DCV+RBV	3/3 (100.00)	2/2 (100.00)	1/1 (100.00)		26/29 (89.66)	4/4 (100.00)	33/36 (91.67)
SOF+SIM	21/21 (100.00)	9/9 (100.00)	12/12 (100.00)			5/5 (100.00)	26/26 (100.00)
SOF+LDP	12/12 (100.00)	6/6 (100.00)	6/6 (100.00)			4/4 (100.00)	16/16 (100.00)
PTVr/OBV+RBV						9/10 (90.00)	9/10 (90.00)
PTVr/OBV+DSV	9/9 (100.00)		9/9 (100.00)				9/9 (100.00)
SOF+DCV	2/2 (100.00)	1/1 (100.00)	1/1 (100.00)		4/4 (100.00)	1/1 (100.00)	7/7 (100.00)
Total	167/174 (95.98)	76/80 (95.00)	91/94 (96.81)	30/31 (96.77)	67/78 (85.90)	42/44 (95.45)	306/327 (93.58)
p-value	0.90	1.00	0.81	–	0.74	1.00	0.56

Note: Italics indicate data on GT 1a/b.

Abbreviations: DCV, daclatasvir; DSV, dasabuvir; GT, genotype; HCV, hepatitis C virus; LDP, ledipasvir; OBV, ombitasvir; PTVr, ritonavir boosted paritaprevir; RBV, ribavirin; SIM, simeprevir; SOF, sofosbuvir; SVR, sustained virologic response.

Table 3 Total cost and average cost (in €) per patient according to genotype

Genotype	Patients	Total	Percentage	Mean	SD
1	174	7,559,389	51.27	43,445	15,430
1a	80	3,616,227	24.53	45,203	14,034
1b	94	3,943,162	26.74	41,949	16,451
2	31	1,269,035	8.61	40,937	2,620
3	78	3,810,101	25.84	48,847	9,405
4	44	2,105,908	14.28	47,862	15,001
Total	327	14,744,433	100.00	45,090	13,603
p-value	0.004

Abbreviation: SD, standard deviation.

Table 4 Total and mean costs for different DAA treatments in patients according to HCV genotype

Anti-HCV regimen	Genotype 1					Genotype 2					Genotype 3					Genotype 4
	n	Total	Percentage	Mean	SD	n	Total	Percentage	Mean	SD	n	Total	Percentage	Mean	SD	n	Total	Percentage	Mean	SD
SOF+RBV						31	1,269,035		40,937	2,620	45	1,855,475	48.70	41,233	630
SOF+LDP+RBV	45	1,886,982	24.96	41,933	7,217											7	300,893	14.29	42,985	5,345
SOF+SIM+RBV	38	2,319,038	30.68	61,027	875											13	787,608	37.40	60,585	992
PTVr/OBV+DSV+RBV	44	1,099,015	4.54	24,978	3,644
SOF+DCV+RBV	3	184,185	2.44	61,395	2,645						29	1,729,192	45.38	59,627	4,071	4	239,213	11.36	59,803	12
SOF+SIM	21	1,254,155	16.59	59,722	3,564											5	299,942	14.24	59,988	1,476
SOF+LDP	12	467,681	6.19	38,973	9,350											4	179,495	8.52	44,874	50
PTVr/OBV+RBV																10	239,209	11.36	23,921	662
PTVr/OBV+DSV	9	229,036	3.03	25,448	0
SOF+DCV	2	119,299	1.58	59,649	0						4	225,434	5.92	56,358	6,448	1	59,548	2.83	59,548	.
Total	174	7,559,389	100.00	43,445	15,430	31	1,269,035	100.00	40,937	2,620	78	3,810,101	100.00	48,847	9,405	44	2,105,908	100.00	47,862	15,001
p-value	<0.0001					–					<0.0001					<0.0001

Abbreviations: DAA, direct antiviral agent; DCV, daclatasvir; DSV, dasabuvir; HCV, hepatitis C virus; LDP, ledipasvir; OBV, ombitasvir; PTVr, ritonavir boosted paritaprevir; RBV, ribavirin; SD, standard deviation; SIM, simeprevir; SOF, sofosbuvir.

Table 5 Total cost and average cost (in €) per patient according to genotype and regimen prescribed; focus on genotype 1

Regimen anti-HCV	Genotype 1a					Genotype 1b
	n	Total	Percentage	Mean	SD	n	Total	Percentage	Mean	SD
SOF+RBV
SOF+LDP+RBV	32	1,343,382	37.15	41,981	7,687	13	543,600	13.79	41,815	6,189
SOF+SIM+RBV	16	9,72,878	26.90	60,805	227	22	1,346,160	34.14	61,189	1,116
PTVr/OBV+DSV+RBV	14	3,46,455	9.58	24,747	3,588	30	752,560	19.09	25,085	3,726
SOF+DCV+RBV	2	1,24,269	3.44	62,134	3,272	1	59,916	1.52	59,916	.
SOF+SIM	9	5,42,536	15.00	60,282	1,100	12	711,619	18.05	59,302	4,666
SOF+LDP	6	2,27,058	6.28	37,843	7,748	6	240,622	6.10	40,104	11,369
PTVr/OBV+RBV
PTVr/OBV+DSV						9	229,036	5.81	25,448	0
SOF+DCV	1	59,649	1.65	59,649		1	596,49	1.51	59,649
Total	80	3,616,227	100.00	45,203	14,034	94	3,943,162	100.00	41,949	16,451
p-value	<0.0001					<0.0001

Abbreviations: DCV, daclatasvir; DSV, dasabuvir; HCV, hepatitis C virus; LDP, ledipasvir; OBV, ombitasvir; PTVr, ritonavir boosted paritaprevir; RBV, ribavirin; SD, standard deviation; SIM, simeprevir; SOF, sofosbuvir.

Table 6 Cost per SVR-12 (in €) according to genotype and treatment regimen

Anti-HCV regimen	Genotype						Total
	1	1a	1b	2	3	4
SOF+RBV				42,301	50,148		46,634
SOF+LDP+RBV	43,883	44,779	41,815			42,985	43,757
SOF+SIM+RBV	66,258	64,859	67,308			65,634	66,099
PTVr/OBV+DSV+RBV	26,167	26,650	25,950				26,167
SOF+DCV+RBV	61,395	62,135	59,916		66,507	59,803	65,230
SOF+SIM	59,722	60,282	59,302			59,988	59,773
SOF+LDP	38,973	37,843	40,104			44,874	40,448
PTVr/OBV+RBV						26,579	26,579
PTVr/OBV+DSV	25,448		25,448				25,448
SOF+DCV	59,649	59,649	59,649		56,359	59,548	57,754
Total	45,266	47,582	43,331	42,301	56,867	50,141	48,184

Abbreviations: DCV, daclatasvir; DSV, dasabuvir; HCV, hepatitis C virus; LDP, ledipasvir; OBV, ombitasvir; PTVr, ritonavir boosted paritaprevir; RBV, ribavirin; SIM, simeprevir; SOF, sofosbuvir; SVR, sustained virologic response.

Table 7 Cost per SVR (in €) and sensitivity analysis

Variable	Cost per SVR
Baseline	48,184
SVR (%)
−2	49,237
−5	50,904
+2	47,176
+5	45,740
Anti-HCV treatment (DAA and/or ribavirin) (%)
−10	43,418
−20	38,652
−30	33,885
−50	24,353
+10	52,951
+20	57,717
+30	62,484
+50	72,016
Direct costs (visits, diagnostic tests, hospitalizations, supportive care)* (%)
−10	48,132
−20	48,080
−30	48,028
+10	48,236
+20	48,289
+30	48,341

Note:

* All costs issues varied at the same time and in the same percentage.

Abbreviations: DAA, direct antiviral agent; HCV, hepatitis C virus; SVR, sustained virologic response.

Table S1 Italian guidelines for the treatment of HCV at the time of study (Documento Società Italiana Studio Fegato-AISF December 17, 2014)¹

Regimen prescribed	Genotype 1a	Genotype 1b	Genotype 2	Genotype 3	Genotype 4
PTVr/OBV+DSV±RBV	PTVr/OBV+DSV+RBV for 24 weeks	12 weeks with RBV	No	No	No
SOF+LDP±RBV	12 weeks with RBV	12 weeks with RBV	No	No	12 weeks with RBV
	24 weeks without RBV	24 weeks without RBV			24 weeks without RBV
PTVr/OBV+RBV	No	No	No	No	24 weeks with RBV
SOF+DCV	12 weeks with RBV	12 weeks with RBV	12 weeks	24 weeks with RBV	12 weeks with RBV
	24 weeks without RBV	24 weeks without RBV	without RBV	preferred regimen	24 weeks without RBV
SOF+RBV	No	No	16–20 weeks	24 weeks suboptimal	No
SOF+SIM	12 weeks with RBV	12 weeks with RBV	No	No	12 weeks with RBV
	24 weeks without RBV	24 weeks without RBV			24 weeks without RBV

Abbreviations: DCV, daclatasvir; DSV, dasabuvir; HCV, hepatitis C virus; LDP, ledipasvir; OBV, ombitasvir; PTVr, ritonavir boosted paritaprevir; RBV, ribavirin; SIM, simeprevir; SOF, sofosbuvir.

Table S2 Drug-related costs (according to Regione Emilia-Romagna)

Treatment regimen	From January 1 to May 31, 2015	From June 1 to August 31, 2015	From September 1 to October 31, 2015
SOF+RBV	40,700+RBV	40,700+RBV	27,839+RBV
SOF+LDP+RBV	44,770+RBV	44,770+RBV	30,622+RBV
SOF+SIM+RBV	60,500+RBV	57,200+RBV	44,338+RBV
PTVr/OBV+DSV+RBV	25,300+RBV	25,300+RBV	25,300+RBV
SOF+DCV+RBV	59,400+RBV	59,400+RBV	46,539+RBV
SOF+SIM	60,500	57,200	44,338
SOF+LDP	44,700	44,700	30,622
PTVr/OBV+RBV	23,276+RBV	23,276+RBV	23,276+RBV
PTVr/OBV+DSV	25,300	25,300	25,300
SOF+DCV	59,400	59,400	46,539

Note: All costs are indicated in Euros.

Abbreviations: DCV, daclatasvir; DSV, dasabuvir; LDP, ledipasvir; OBV, ombitasvir; PTVr, ritonavir boosted paritaprevir; RBV, ribavirin; SIM, simeprevir; SOF, sofosbuvir.

Table S3 Laboratory code

Code (according to the Regione Liguria classification)	Description	Cost/procedure
Laboratory costs
90.62.2	Complete blood cell count	3.35
91.19.4	HCV RNA quantification	9.03
90.09.2	AST	0.77
90.04.5	ALT	0.77
90.10.4	Bilirubin total	0.87
90.10.5	Bilirubin direct/indirect	0.90
90.25.5	GGT	0.83
90.16.3	Creatinine	0.77
90.23.5	Alkaline phosphatase	0.66
90.75.4	INR	1.75
90.38.4		4.95
Outpatient service visits
	Initial visit	20.66
	Subsequent visit	12.90

Note: All costs are indicated in Euros.

Abbreviations: HCV, hepatitis C virus; INR, international normalized ratio; GGT, gamma glutamil transferase; AST, aspartate transaminase; ALT, alanine transaminase.

Table S4 Other costs (indicated in Euros)

DRG code	Clinical category	Threshold	Financial cost
203	Liver tumor (HCC)	35 days	€4,085+175 a day each day >threshold
205	Liver cirrhosis complicated	27 days	€3,760+157 a day per day >threshold

Abbreviation: DRG, diagnosis related group.

Table S5 Cost of drugs

Drug	Cost
Albumin	€43.49 per unit (VAT included)
Red blood cells	€153 per unit (VAT included)
Erythropoietin (beta epoetin) 30,000 IU/mL	€90.75 per unit (VAT included)
Ribavirin 200 mg	€23.80 per unit (VAT included) 168 tablets

Table S6 Patients’ features according to HCV treatment

Patients’ main features	SOF+RBV	SOF+LDP+RBV	SOF+SIM+RBV	PTVr/OBV+DSV+RBV	SOF+DCV+RBV	SOF+SIM	SOF+LDP	PTVr/OBV+RBV	PTVr/OBV+DSV	SOF+DCV	p-value
	n=76	n=52	n=51	n=44	n=36	n=26	n=16	n=10	n=9	n=7
Age, years	55 (51–71)	55 (52–59)	55 (52–61)	55 (51–63)	55 (52–55)	57 (51–62)	56 (51–64)	54 (51–59)	56 (51–60)	57 (54–62)	0.43
Gender (male)	55 (72.73)	41 (78.85)	38 (774.51)	32 (72.73)	31 (86.11)	8 (30.77)	13 (81.25)	7 (70.00)	4 (44.44)	4 (57.14)	<0.0001
Fibrosis stage											<0.0001
1	1 (1.32)	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	1 (3.85)	1 (6.25)	0 (0.00)	1 (11.11)	0 (0.00)
2	1 (1.32)	0 (0.00)	1 (1.96)	0 (0.00)	0 (0.00)	1 (3.85)	2 (12.50)	0 (0.00)	0 (0.00)	1 (14.29)
3	19 (25.00)	2 (3.85)	8 (15.69)	6 (13.64)	1 (2.87)	9 (34.62)	7 (43.75)	4 (40.00)	6 (66.67)	2 (28.57)
4	55 (72.37)	50 (96.15)	42 (82.35)	38 (86.36)	35 (97.22)	15 (57.69)	6 (37.50)	6 (60.00)	2 (22.22)	4 (57.14)
Genotype											<0.0001
1	0 (0.00)	45 (86.54)	38 (74.51)	44 (100.00)	3 (8.33)	21 (80.77)	12 (75.00)	0 (0.00)	9 (100.00)	2 (28.57)
2	31 (40.79)	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)
3	45 (59.21)	0 (0.00)	0 (0.00)	0 (0.00)	29 (80.56)	0 (0.00)	0 (0.00)	0 (0.00)	0 (0.00)	4 (57.14)
4	0 (0.00)	7 (13.46)	13 (25.49)	0 (0.00)	4 (11.11)	5 (19.23)	4 (25.00)	10 (100.00)	0 (0.00)	1 (14.29)
Comorbidities	37 (48.68)	39 (75.00)	27 (52.94)	22 (50.00)	24 (66.67)	4 (15.38)	7 (43.75)	2 (20.00)	2 (22.22)	4 (57.14)	<0.0001
Previous treatment HCV	35 (46.05)	29 (55.77)	37 (72.55)	27 (61.36)	18 (50.00)	7 (26.92)	5 (31.25)	4 (40.00)	8 (88.89)	4 (57.14)	0.002

Note: Data are presented as median (interquartile range) for continuous variables and as frequency (%) for categorical variables.

Abbreviations: DCV, daclatasvir; DSV, dasabuvir; HCV, hepatitis C virus; LDP, ledipasvir; OBV, ombitasvir; PTVr, ritonavir boosted paritaprevir; RBV, ribavirin; SIM, simeprevir; SOF, sofosbuvir.

Table S7 Correlates of the total cost: results of multivariate analyses

Variables	β	95% CI	p-value
HCV treatment
PTVr/OBV+DSV+RBV	–	–	–
PTVr/OBV+DSV	1,863	−752; 4,477	0.16
PTVr/OBV+RBV	−2,222	−4,980; 536	0.11
SOF+DCV	29,988	26,724; 33,253	<0.0001
SOF+DCV+RBV	31,922	29,161; 34,683	<0.0001
SOF+LDP	16,392	14,277; 18,506	<0.0001
SOF+LDP+RBV	16,954	15,537; 18,372	<0.0001
SOF+RBV	10,091	6,754; 13,429	<0.0001
SOF+SIM	30,481	28,415; 32,546	<0.0001
SOF+SIM+RBV	30,173	28,365; 31,981	<0.0001
Gender (female vs male)	−510	−1,405; 386	0.26
Fibrosis grade
1	–	–	–
2	2,422	−2,067; 6,912	0.29
3	2,152	−1,435; 5,738	0.24
4	1,825	−1,772; 5,422	0.32
Genotype
1	–	–	–
2	2,563	−583; 5,708	0.11
3	749	−1,891; 3,389	0.58
4	573	−787; 1,932	0.41
Comorbidites (yes vs no)	623	−201; 1,446	0.14
Prior anti-HCV treatment (yes vs no)	712	−100; 1,525	0.09
Time start treatment	−4,726	−5,682; −3,769	<0.0001

Abbreviations: CI, confidence interval; DCV, daclatasvir; DSV, dasabuvir; HCV, hepatitis C virus; LDP, ledipasvir; OBV, ombitasvir; PTVr, ritonavir boosted paritaprevir; RBV, ribavirin; SIM, simeprevir; SOF, sofosbuvir.

AISFDocumento di indirizzo dell’Associazione Italiana per lo Studio del Fegato per l’uso razionale di antivirali diretti di seconda generazione nelle categorie di pazienti affetti da epatite C cronica ammesse alla rimborsabilità in Italia AISF [released 17 December 2014, updated December 2016] Available from: http://www.webaisf.org/pubblicazioni/documento-aisf-hcv-2016.aspxAccessed November 29, 2016

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