The cost of successful antiviral therapy in hepatitis C patients: a comparison of IFN-free versus IFN-based regimens at an individual patient level in Australia

Figures & data

Table 1 Baseline characteristics and conditions

Age starting treatment (years), mean ± SD	46.7 ± 9.68
Male, n (%)	16 (53.3)
Smoker, n (%)	11(36.7)
BMI (kgm-^2), mean ± SD	26.9 ± 5.4
History of IVDU, n (%)	17 (56.7)
Charlson comorbidity index, mean ± SD	1.9 ± 1.3
Selected comorbidities, n (%)
Diabetes mellitus	5 (16.7)
Diabetes mellitus with complications	3 (10.0)
Chronic kidney disease	2 (6.7)
Chronic hepatitis B	1 (3.3)
Connective tissue disease	3 (10)
COPD	1 (3.3)
Hypertension	4 (13.3)
Psychiatric history (e.g., depression), n (%)	10 (33.3)
Previous CHC treatment (any history), n (%)	5 (16.7)
Previous liver biopsy, n (%)	3 (10)
Fibroscan score (kPA), mean ± SD	8.5 ± 4.3
Fibro scan score ≥14 kPA, n (%)	3 (10)
Cirrhosis, n (%)	5 (16.7)
Genotype, n (%)
1	17 (56.7)
1a	9 (30.0)
1b	7 (23.3)
2	1 (3.3)
3	10 (33.3)
6	2 (6.7)
Race, n (%)
Caucasian	20 (66.7)
Asian	8 (26.7)
Other	2 (6.7)
Baseline
Viral load, n (%)
<400 000 (IUmL^−1)	10 (33.3)
>400 000 (IUmL^−1)	20 (66.7)
AST (UL^−1), mean ± SD	65.4 ± 50.9
ALT (UL^−1), mean ± SD	98.6 ± 85.6

Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; BMI, body mass index; CHC, chronic hepatitis C; COPD, chronic obstructive pulmonary disease; IVDU, intravenous drug use; SD, standard deviation.

Table 2 Treatment characteristics

	All patients (n=30)	GT1 patients (n=17)	GT3 patients (n=10)
Study perioda (days), mean ± SD	431.8 ± 108.9	433.2 ± 125.1	420.5 ± 91.8
Duration of treatment (days), average ± SD	236.6 ± 81.9	230.2 ± 81.1	233.8 ± 85.0
RVR, n (%)	23 (76.7)	16 (94.1)	6 (60)
Treatment received, n (%)
Telaprevir, Peg-IFN, RBV	11 (36.7)	11 (64.7)	0 (0)
Boceprevir, Peg-IFN, RBV	4 (13.3)	4 (23.5)	0 (0)
Simeprevir, Peg-IFN, RBV	1 (3.3)	1 (5.9)	0 (0)
Peg-IFN, RBV	14 (46.7)	1 (5.9)	10 (100)
Patients requiring dose reductions, n (%)	8 (26.7)	7 (41.2)	1 (10)
RBV dose reduction, n (%)b	7 (23.3)	6 (35.3)	0 (0)
Peg-IFN dose reduction, n (%)	3 (10)	2 (11.8)	1 (10)
Patients requiring drug cessation (temporary), n (%)	3 (10.0)	2 (11.8)	1 (10)
Peg-IFN drug cessation (temporary), n (%)	2 (6.7)	1 (5.9)	1 (10)
Telaprevir drug cessation (temporary), n (%)	1 (3.3)	1 (5.9)	0 (0)
RBV drug cessation (temporary), n (%)	1 (3.3)	1 (5.9)	0 (0)
Patients requiring drug cessation (permanent), n (%)	2 (6.7)	1 (5.9)	1 (10)
Peg-IFN drug cessation (permanent)	2 (6.7)	1 (5.9)	1 (10)
RBV drug cessation (permanent)	2 (6.7)	1 (5.9)	1 (10)

Notes:

a Study period defined as from first day of treatment to clinic discharge.

b RBV dose reduction was required for one GT6 patient.

Abbreviations: Peg-IFN, pegylated-interferon; RBV, ribavirin; RVR, rapid virological response rate (undetectable serum HCV RNA level at week 4 of treatment); SD, standard deviation.

Table 3 Medical resource utilization and costs

Resource item	Patients, n (%)	Total, n	Mean ± SD (per patient)	Mean costs (AUD) ± SD (per patient)
Bloods testsa	30 (100)	496	16.53 ± 8.38	1811.28 ± 580.10
Ultrasound	12 (40)	28	0.93 ± 1.28	86.59 ± 124.55
Chest X-ray	7 (23)	7	0.20 ± 0.41	9.43 ± 20.28
CT scan	6 (20)	8	0.27 ± 0.58	79.34 ± 182.43
MRI	1 (3.3	1	0.03 ± 0.18	14.93 ± 81.79
Ultrasound-guided aspiration	1 (3.3)	1	0.03 ± 0.18	1.245 ± 6.82
Bone Scan	1 (3.3)	1	0.03 ± 0.18	20.02 ± 109.67
ECHO	1 (3.3)	1	0.03 ± 0.18	7.69 ± 42.11
ECG	4 (13.3)	4	0.13 ± 0.35	2.07 ± 5.38
Urinalysis	6 (20)	8	0.27 ± 0.64	5.48 ± 13.15
Feces exam	1 (3.3)	1	0.03 ± 0.18	1.12 ± 6.12
MRCP	1 (3.3)	1	0.03 ± 0.18	14.93 ± 81.79
Sputum MCS	1 (3.3)	1	0.03 ± 0.18	1.13 ± 6.16
Respiratory function test	1 (3.3)	1	0.03 ± 0.18	1.19 ± 6.51
Exercise stress test	1 (3.3)	1	0.03 ± 0.18	5.07 ± 27.79
Gastroscopy	1 (3.3)	1	0.03 ± 0.18	5.90 ± 32.33
Colonoscopy	1 (3.3)	1	0.03 ± 0.18	11.15 ± 61.04
Capsule endoscopy	1 (3.3)	1	0.03 ± 0.18	67.97 ± 372.3
Surgical procedure	2 (6.7)	3	0.10 ± 0.40	38.27 ± 147.70
Specialty referrals (all)	17 (56.7)	25	0.83 ±0.95	130.20 ±138.80
Rheumatology	2 (6.7)	2	0.07 ±0.25	10.06 ±38.28
Cardiology	2 (6.7)	2	0.07 ±0.25	10.06 ±38.28
Psychiatry	6 (20)	6	0.2 ±0.41	52.06 ± 105.90
Haematology	1 (3.3)	1	0.03 ±0.18	5.03 ±27.55
Gastroenterology	2 (6.7)	2	0.07 ±0.25	10.06 ±38.28
Ophthalmology	1 (3.3)	1	0.03 ±0.18	2.85 ±15.62
Dermatology	2 (6.7)	2	0.07 ±0.25	5.70 ± 21.70
Infectious disease	1 (3.3)	1	0.03 ±0.18	5.03 ±27.55
Thoracic medicine	1 (3.3)	1	0.03 ±0.18	5.03 ±27.55
Gynaecology	2 (6.7)	2	0.07 ±0.25	5.70 ± 21.70
Endocrinology	1 (3.3)	1	0.03 ±0.18	5.03 ±27.55
Nephrology	1 (3.3)	1	0.03 ±0.18	5.03 ±27.55
Cardiothoracic surgery	1 (3.3)	1	0.03 ±0.18	2.85 ±15.62
General surgery	1 (3.3)	1	0.03 ±0.18	2.85 ±15.62
Colorectal surgery	1 (3.3)	1	0.03 ±0.18	2.85 ±15.62
Liver clinic visits	30 (100)	344	11.47 ±3.74	N/A
ER visits	7 (23.3)	12	0.40 ±0.86	N/A
Hospital admissions	2 (6.7)	4	0.13 ±0.51	N/A
Total				$2,318.28±$1,104.20

Note:

a Blood test costs per patient equal the sum of all individual item costs (e.g., full blood count, C-reactive protein).

Abbreviations: AUD, Australian dollars; CT, computed tomography; ECG, electrocardiogram; ECHO, echocardiogram; ER, emergency room; MCS, microscopy, culture and sensitivity; MRCP, magnetic resonance cholangiopancreatography; MRI, magnetic resonance imaging; N/A, not applicable; SD, standard deviation.

Table 4 Comparison of demographic and treatment characteristics

	GT1 patients		GT3 patients
	IFN-based treatment (n=17)	IFN-free treatment (SOF + LDV)a (n=100)	IFN-based treatment (n=10)	IFN-free treatment (SOF + DCV)b (n=100)
Demographics
Genotype, %
1a	53	67	N/A	N/A
1b	41	31	N/A	N/A
Unconfirmed	6	2	N/A	N/A
Male, %	53	59	60	57
Mean BMI	28	27	26	27
Cirrhosis, %	24	16	10	19
Treatment
Treatment duration (weeks), mean ± SD	32.9 ± 11.6	12.0 ± 0	33.4 ±12.15	14.28 ± 4.7

Notes:

a Derived from ION-I trial (Afdhal et al¹⁸).

b Derived from ALLY-3 trial (Nelson et al¹⁹).

Abbreviations: BMI, body mass index; DCV, daclatasvir; GT1, genotype 1; GT3, genotype 3; IFN, interferon; LDV, ledipasvir; N/A, not applicable; SD, standard deviation; SOF, sofosbuvir.

Table 5 Comparison of medical resource utilization and costs

	GT1 patients		GT3 patients
	IFN-based treatment	IFN-free treatment (SOF/LDV)	IFN-based treatment	IFN-free treatment (SOF/DCV)
Resource itema
Liver clinic visits, mean ± SD	12.5 ± 4.61	4.16 ± 0.37	10.5 ± 2.46	4.76 ± 1.58
ER presentations, mean ± SD	0.35 ± 0.86	0.01 ± 0.1	0.50 ± 0.97	0.02 ± 0.14
Hospital admissions, mean ± SD	0.07 ± 0.26	0 ± 0	0.10 ± 0.32	0 ± 0
Blood tests, mean ± SD	18 ± 9.07	4.18 ± 0.46	13.5 ± 5.56	4.78 ± 1.62
Specialty referrals, mean ± SD	0.80 ± 0.77	0.01 ± 0.10	0.60 ± 0.97	0 ± 0
Costs (AUD)a
Blood tests, mean ± SD	$1,946.97 ± 590.87	$476.03 ± 8.41	$1,555.69 ± 399.33	$486.25 ± 27.91
Other resources, mean ± SD	$147.81 ± 245.25	$2.15 ± 21.49	$168.89 ± 413.35	$21.15 ± 43.88
Initial specialist visit, mean ± SD	$129.60 ± 130.92	$1.51 ± 15.09	$105.89 ± 147.65	$0 ± 0
Antiviral drug costs, mean ± SD	$45,432.00 ± 13622.76	$66,341.07 ± 0	$11,972.09 ± 4,698.47	$98,588.33 ± 33,353.83
Total costs, mean ± SD	$47,656.39 ± 13,914.96	$66,820.76 ± 42.57	$13,802.06 ± 4,872.90	$99,096.42 ± 33,422.64

Note:

a Per patient.

Abbreviations: AUD, Australian dollars; DCV, daclatasvir; ER, emergency room; GT1, genotype 1; GT3, genotype 3; IFN, interferon; LDV, ledipasvir; SD, standard deviation; SOF, sofosbuvir.

Table S1 Adverse events for patients receiving IFN-based therapy (n=30)

Adverse events (per patient), mean ± SD 14.4±3.76
Adverse events requiring medical treatment (per patient), mean ± SD 2.2±2.16
Common adverse event	Patients, n (%)	Requiring medical treatment, n (%)a
Fatigue	24 (80)	0
Rash	22 (73.3)	13 (59.1)
Mood change	22 (73.3)	3 (13.6)
Depression	9 (30)	2 (22.2)
Irritability	16 (53.3)	1 (6.25)
Pruritus	18 (60)	0
Upper respiratory tract symptoms	16 (53.3)	4 (25)
Weight loss	15 (50)	0
Headache	14 (46.7)	0
Sleep disturbance	12 (40)	5 (41.7)
Flu-like symptoms (non-specific)	12 (40)	0
Myalgia	11 (36.7)	0
Severe hematological adverse event
Hemoglobin
Hb 80–99 (gL^−1)	9 (30)	1 (11.1)
Hb <80 (gL^−1)	1 (3.3)	0
Neutrophils
0.5–0.99 (×10^9 L^−1)	17 (56.6)	0
<0.5 (×10^9 L^−1)	3 (10)	0
Platelets
50–99 (×10^9 L^−1)	12 (40)	0
<50 (×10^9 L^−1)	2 (6.7)	1 (50)
Serious adverse events (requiring hospital admission)	2 (6.7)	2 (100)
Immune thrombocytopenic purpura	1 (3.3)	1 (100)
Osteomyelitis	1 (3.3)	1 (100)

Note:

a Percentage of total number of patients who experienced the adverse event.

Abbreviations: Hb, hemoglobin; IFN, interferon.

Table S2 Emergency department presentations for patients treated with IFN-based therapy (n=30)

Reason for presentation	Number of presentations, n
Cough + fever	1
Bleedinga	1
Urinary frequency	1
Anxiety	1
Musculoskeletal chest painb	3
Flu-like symptoms	1
Dizziness	1
Dysuria	1
Nausea/vomiting	1

Notes:

a Epistaxis and mucosal bleeding, secondary to severe thrombocytopenia.

b Related to chronic rib osteomyelitis.

Abbreviation: IFN, interferon.

Table S3 Adverse events for GT1 patients

Common adverse events	Patients receiving IFN-based therapy (n=17) N (%)	Theoretical patients receiving SOF/LDV (n=100)a N (%)
Fatigueb	14 (82)	28 (28)
Headache	11 (65)	25 (25)
Insomnia	10 (59)	8 (8)
Nausea	7 (41)	11 (11)
Diarrhea	5 (29)	11 (11)
Rash	9 (53)	7 (7)
Irritability	8 (47)	5 (5)
Cough	9 (53)	3 (3)
Pruritus	8 (73)	5(5)
Hematological adverse events
Hb
<100 (gL^−1)	9 (53)	0 (0)
<85 (gL^−1)	3 (18)	0(0)
Lymphocytes
<0.35 (×10^9 L^−1)	0 (0)	0(0)
Neutrophil <0.75 (×10^9 L^−1)	7 (41)	1 (1)
Platelet count <50 (×10^9 L^−1)	2 (12)	1 (1)

Notes:

a Derived from ION-1 trial (Afdhal et al¹).

b To facilitate comparison, cases of “asthenia” were included under fatigue.

Abbreviations: GT1, genotype 1; Hb, hemoglobin; IFN, interferon; LDV, ledipasvir; SOF, sofosbuvir.

Table S4 Adverse events for GT3 patients

Common adverse events	Patients receiving IFN-based therapy (n=10) N (%)	Theoretical patients receiving SOF/DCV (n=100)a N (%)
Headache	3 (30)	20 (20)
Fatigue	7 (70)	19 (19)
Nausea	4 (40)	12 (12)
Diarrhea	2 (20)	9 (9)
Insomnia	3 (30)	6 (6)
Abdominal pain	3 (30)	5 (5)
Arthralgia	5 (50)	5 (5)
Hematological adverse events
Hb
<90 (gL^−1)	0 (0)	0 (0)
Lymphocytes
<0.5 (×10^9 L^−1)	1 (10)	1 (1)
Neutrophil <0.75 (×10^9 L^−1)	6 (60)	0 (0)
Platelet count <50 (×10^9 L^−1)	0 (0)	1 (1)

Note:

a Derived from ALLY-3 trial (Nelson et al²)

Abbreviations: DCV, daclatasvir; GT3, genotype 3; Hb, hemoglobin; IFN, interferon; SOF, sofosbuvir.

Table S5 Comparison of medical resource utilization and costs for GT1 patients

Resource item	Patients receiving IFN-based therapy (n=17)		Theoretical patients receiving SOF/LDV (n=100)
	Mean number per patient ± SD	Mean cost per patient ± SD	Mean number per patient ± SD	Mean cost per patient ± SD
Blood tests	18 ± 9.1	$1943.63 ± 586.47	4.16 ± 0.37	$590.21 ±1 68.75
Ultrasound	0.06 ± 0.24	$6.55 ± 26.99	0 ± 0	$0 ± 0
CXR^¶	0.24 ± 0.44	$11.09 ± 20.62	0.01 ± 0.1	$0.57 ± 4.72
ECHO	0.06 ± 0.24	$13.57 ± 55.94	0 ± 0	$0 ± 0
CT scan	0.24 ± 0.56	$68.83 ± 163.93	0 ± 0	$0 ± 0
ECG^¶	0.18 ± 0.39	$2.74 ± 6.11	0.01 ± 0.1	$0.16 ± 1.56
Urinalysis	0.12 ± 0.33	$2.42 ± 6.82	0 ± 0	$0 ± 0
BMAT	0.06 ± 0.24	$5.19 ± 21.40	0 ± 0	$0 ± 0
MRCP	0.06 ± 0.24	$26.35 ± 103.66	0 ± 0	$0 ± 0
Stress ECG^¶	0 ± 0	$0 ± 0	0.01 ± 0.1	$1.52 ± 15.22
Specialist Referral	0.80 ± 0.77	$120.73 ± 134.46	0.01 ± 0.1	$1.51 ± 15.09
Psychiatry	0.24 ± 0.44	$61.25 ± 113.81	0 ± 0	$0 ± 0
Dermatology	0.12 ± 0.33	$10.06 ± 28.41	0 ± 0	$0 ± 0
Rheumatology	0.06 ± 0.24	$8.88 ± 36.60	0 ± 0	$0 ± 0
Gastroenterology	0.06 ± 0.24	$8.88 ± 36.60	0 ± 0	$0 ± 0
Cardiology^¶	0.06 ± 0.24	$8.88 ± 36.60	0.01 ± 0.1	$1.51 ± 15.09
Hematology	0.06 ± 0.24	$8.88 ± 36.60	0 ± 0	$0 ± 0
Endocrinology	0.06 ± 0.24	$8.88 ± 36.60	0 ± 0	$0 ± 0
Liver clinic visits	12.5 ± 4.61	N/A	4.16 ± 0.37	N/A
ER presentations	0.35 ± 0.86	N/A	0.01 ± 0.1	N/A
Hospital admissions	0.07 ± 0.26	N/A	0 ± 0	N/A

Note: The single serious adverse event (chest pain) for theoretical patients receiving SOF/LDV was predicted to result in an ECG, CXR, stress ECG, and a cardiology referral.

Abbreviations: BMAT, bone marrow aspirate and trephine; CT, computed tomography; CXR, chest x-ray; ECG, electrocardiogram; ECHO, echocardiogram; ER, emergency room; GT1, genotype 1; IFN, interferon; LDV, ledipasvir; MRCP, magnetic resonance cholangiopancreatography; N/A, not applicable; SD, standard deviation; SOF, sofosbuvir.

Table S6 Comparison of medical resource utilization and costs for GT3 patients

Resource item	Patients receiving IFN-based therapy (n=10)		Theoretical patients receiving SOF/DCV (n=100)
	Mean number per patient ± SD	Mean cost per patient ± SD	Mean number per patient ± SD	Mean cost per patient ± SD
Blood tests	13.5 ± 5.56	$1555.69 ± 399.33	4.16 ± 0.37	$486.25 ± 27.95
Ultrasound	0.10 ± 0.32	$3.75 ± 11.84	0 ± 0	$0 ± 0
CXR^¶	0.30 ± 0.48	$15.72 ± 23.58	0 ± 0	$0 ± 0
CT scan	0.10 ± 0.32	$29.50 ± 93.29	0 ± 0	$0 ± 0
ECG^¶	0.10 ± 0.32	$1.56 ± 4.92	0 ± 0	$0 ± 0
Urinalysis	0.10 ± 0.32	$2.06 ± 6.50	0 ± 0	$0 ± 0
Bone scan	0.10 ± 0.32	$66.74 ± 200.23	0 ± 0	$0 ± 0
Sputum MCS	0.10 ± 0.32	$3.38 ± 10.67	0 ± 0	$0 ± 0
RFTs	0.10 ± 0.32	$3.57 ± 11.27	0 ± 0	$0 ± 0
Rib resection	0.10 ± 0.32	$35.67 ± 112.78	0 ± 0	$0 ± 0
Stress ECG^¶	0.10 ± 0.32	$15.22 ± 48.11	0 ± 0	$0 ± 0
Specialist Referral	0.60 ± 0.97	$105.89 ± 147.65	0 ± 0	$0 ± 0
Psychiatry	0.20 ± 0.42	$52.06 ± 109.75	0 ± 0	$0 ± 0
Cardiology	0.10 ± 0.32	$15.09 ± 47.72	0 ± 0	$0 ± 0
Cardiothoracic surgery	0.10 ± 0.32	$8.56 ± 27.05	0 ± 0	$0 ± 0
Thoracic medicine	0.10 ±0.32	$15.09 ± 47.72	0 ± 0	$0 ± 0
Infectious diseases	0.10 ± 0.32	$15.09 ± 47.72	0 ± 0	$0 ± 0
Liver clinic visits	10.5 ± 2.46	N/A	4.76 ± 1.58	N/A
ER presentations	0.50 ± 0.97	N/A	0.02 ± 0.14	N/A
Hospital admissions	0.10 ± 0.32	N/A	0 ± 0	N/A

Abbreviations: CT, computed tomography; CXR, chest x-ray; DCV, daclatasvir; ECG, electrocardiogram; ER, emergency room; GT3, genotype 3; IFN, interferon; MCS, microscopy, culture and sensitivities; N/A, not applicable; RFTs, respiratory function tests; SD, standard deviation; SOF, sofosbuvir.

AfdhalNZeuzemSKwoPION-1 InvestigatorsLedipasvir and sofosbuvir for untreated HCV genotype 1 infectionN Engl J Med2014370201889189824725239

 PubMed Web of Science ®Google Scholar

NelsonDRCooperJNLalezariJPALLY-3 Study TeamAll-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with genotype 3 infection: ALLY-3 phase III studyHepatology20156141127113525614962

 PubMed Web of Science ®Google Scholar

AfdhalNZeuzemSKwoPION-1 InvestigatorsLedipasvir and sofosbuvir for untreated HCV genotype 1 infectionN Engl J Med2014370201889189824725239

 PubMed Web of Science ®Google Scholar

NelsonDRCooperJNLalezariJPALLY-3 Study TeamAll-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with genotype 3 infection: ALLY-3 phase III studyHepatology20156141127113525614962

 PubMed Web of Science ®Google Scholar