Economic evaluation of ombitasvir/paritaprevir/ritonavir and dasabuvir for the treatment of chronic genotype 1 hepatitis c virus infection

Figures & data

Figure 1. Natural history model schematic. HCV, hepatitis C virus.

Table 1. Summary of non-treatment-specific variables for those with chronic genotype 1 hepatitis C virus.

Variable	Base-case value	Source
Time horizon	70 years	The time horizon is essentially a lifetime time horizon, consistent with Hartwell et al.^10
Proportion of genotype 1 patients who are genotype 1a	68.8%	Harris et al.^37
Distribution of treatment-experienced patients by prior response to treatment
Null response	30%	NICE Simeprevir STA^38
Partial response	30%	′′
Relapse after response	40%	′′
Patient characteristics
Treatment-naive
Initial fibrosis distribution
Mild (F0–F1)	46.0%	Hartwell et al.^10
Moderate (F2–F3)	44.0%	′′
CC (compensated cirrhosis, F4)	10.0%	′′
Age (years)	40
Male	70.0%
Treatment-experienced
Initial fibrosis distribution
Mild (F0–F1)	33.0%	Hartwell et al.^10
Moderate (F2–F3)	35.0%	′′
CC (compensated cirrhosis, F4)	32.0%	′′
Age (years)	45
Male	70.0%
Transition probabilities (annual)
Fibrosis progression
Mild-to-moderate	0.025	Wright et al.^39, Grieve et al.^40, Shepherd et al.^35, Hartwell et al.^10
Moderate-to-CC	0.037	′′
Nonfibrosis progression
Recovered, no HCV, history of severe fibrosis (CC) to HCC	0.012	Cardoso et al.^41
CC to DCC	0.039	Fattovich et al.^42, Wright et al.^39, Shepherd et al.^35, Hartwell et al.^10
CC to HCC (first year)	0.014	′′
DCC to HCC (first year)	0.014	′′
Liver transplant
DCC to liver transplant (first year)	0.020	Grieve et al.^40, Wright et al.^39, Shepherd et al.^35, Hartwell et al.^10
HCC to liver transplant (first year)	0.020	Wright et al.^39, expert opinion implied in Hartwell et al.^10
Liver-related mortality
DCC to liver death	0.130	Fattovich et al.^42, Wright et al.^39, Grieve et al.^40, Shepherd et al.^35, Hartwell et al.^10
Liver transplant to liver death	0.150	Hartwell et al.^10, Grieve et al.^40
After liver transplant to liver death	0.057	Shepherd et al.^35, Hartwell et al.^10, Bennett et al.^43
HCC first year to liver death	0.430	Fattovich et al.^42, Wright et al.^39, Shepherd et al.^35, Hartwell et al.^10
HCC subsequent year to liver death	0.430
Viral reinfection	0.010	Expert opinion
Background age- and sex-adjusted probability of death,   annual	variable	Office for National Statistics, National life tables for the UK, based on data for the years 2010–2012
Disease-related costs (2013 £)
Health state direct medical care costs
Mild	£160	Hartwell et al.^10*
Moderate	£589	Backx et al.^44
CC (chronic HCV)	£914	′′
Recovered, no HCV, history of mild fibrosis	£58	′′
Recovered, no HCV, history of moderate fibrosis	£58	′′
Recovered, no HCV, history of severe fibrosis (CC)	£586	′′
DCC	£12,333	Hartwell et al.^10*
HCC (first year)	£10,990	′′
HCC (subsequent year)	£10,990	′′
Liver transplant (first year)	£49,749	′′
Liver transplant (subsequent year)	£1873	′′
Health-state-related utilities
Mild	0.77	Grieve et al.^40, Wright et al.^39, Shepherd et al.^35*, Hartwell et al.^10*
Moderate	0.66	′′
CC (chronic HCV)	0.55	′′
Recovered, no HCV, history of mild fibrosis	0.82	+0.05 added to mild fibrosis health state. Utility aligned with Grieve et al.^40, Wright et al.^39, Shepherd et al.^35*, Hartwell et al.^10*
Recovered, no HCV, history of moderate fibrosis	0.71	+0.05 added to moderate fibrosis health state
Recovered, no HCV, history of severe fibrosis (CC)	0.60	+0.05 added to severe fibrosis health state. Utility aligned with Shepherd et al.^35*, as referenced in Table 34 of Hartwell et al.^10*
DCC	0.45	Grieve et al.^40, Wright et al.^39, Shepherd et al.^35*, Hartwell et al.^10*
HCC (first year)	0.45	′′
HCC (subsequent year)	0.45	′′
Liver transplant (first year)	0.45	Hartwell et al.^10*
Liver transplant (subsequent year)	0.67	Wright et al.^39, Hartwell et al.^10*

CC, compensated cirrhosis; DCC, decompensated cirrhosis; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; NICE, National Institute for Health and Care Excellence; STA, single technology appraisal; UK, United Kingdom.

* Shepherd et al.³⁵ and Hartwell et al.¹⁰, used costs derived from a randomized clinical trial in mild HCV and a supplemental observational data study³⁹.

Table 2. Sustained virologic response rates for those with chronic genotype 1 hepatitis C virus infection by treatment regimen and fibrosis stage: base-case values.

Treatment regimen	Mild fibrosis	Moderate fibrosis	Compensated cirrhosis
Treatment naive
OMB/PTV/r + DSV ± RBV	97.2%	97.2%	96.3%
PegIFN/RBV	45.6%	43.5%	33.3%
SOF + PegIFN/RBV	91.7%	91.7%	80.8%
TPV + PegIFN/RBV	81.3%	71.6%	61.9%
BOC + PegIFN/RBV	65.9%	65.9%	31.3%
Treatment experienced
OMB/PTV/r + DSV ± RBV	97.4%	97.4%	97.2%
PegIFN/RBV	14.0%	17.3%	14.3%
TPV + PegIFN/RBV	58.5%	68.3%	48.6%

BOC, boceprevir; DSV, dasabuvir; OMB, ombitasvir; PegIFN, pegylated interferon; PTV, paritaprevir; r, ritonavir; RBV, ribavirin; SOF, sofosbuvir; TPV, telaprevir.

Table 3. Adverse event rates for those with chronic genotype 1 hepatitis C virus infection by treatment regimen and fibrosis stage: base-case values.

Treatment regimen	Anemia	Rash	Depression	Neutropenia	Thrombocytopenia
Treatment naive
OMB/PTV/r + DSV ± RBV*	3.9% (9.6%)	7.9% (13.5%)	0.0% (6.0%)	0.1% (1.4%)	0.1% (0.3%)
PegIFN/RBV	19.4%	24.4%	21.9%	14.7%	0.6%
SOF + PegIFN/RBV	20.8%	18.0%	9.5%	20.2%	0.3%
TPV + PegIFN/RBV	37.2%	36.6%	18.2%	10.2%	2.2%
BOC + PegIFN/RBV	49.5%	25.3%	22.6%	29.3%	3.3%
Treatment Experienced
OMB/PTV/r + DSV ± RBV*	3.7% (9.6%)	6.4% (13.5%)	0.0% (6.0%)	0.0% (1.4%)	0.0% (0.3%)
PegIFN/RBV	15.2%	18.9%	14.4%	14.4%	3.0%
TPV + PegIFN/RBV	29.7%	37.2%	9.0%	12.9%	4.4%

BOC, boceprevir; DSV, dasabuvir; OMB, ombitasvir; PegIFN, pegylated interferon; PTV, paritaprevir; r, ritonavir; RBV, ribavirin; SOF, sofosbuvir; TPV, telaprevir.

* Value in parentheses is the adverse event rate for patients with GT1a disease and cirrhosis who receive 24-week therapy.

Table 4. Treatment duration for those with chronic genotype 1 hepatitis C virus infection.

Treatment regimen	Duration (mean weeks)*		Source
Treatment naive
OMB/PTV/r + DSV ± RBV	11.9 (no cirrhosis)	19.8 (cirrhosis)	Trial publications†
SOF + PegIFN/RBV	11.9		Lawitz et al.^46 [NEUTRINO]
TPV + PegIFN/RBV‡	10.4 + 28.3		Jacobson et al.^47 [ADVANCE]
BOC + PegIFN/RBV‡	19.9 + 27.4		Poordad et al.^48 [SPRINT-2]
PegIFN/RBV	37.4		Jacobson et al.^47 [ADVANCE]
Treatment experienced
OMB/PTV/r + DSV ± RBV	11.9 (no cirrhosis)	19.8 (cirrhosis)	Trial publications†
TPV + PegIFN/RBV^‡	9.7 + 39.0		Zeuzem et al.^49 [REALIZE]
PegIFN/RBV	33.1		Zeuzem et al.^49 [REALIZE]

BOC, boceprevir; DSV, dasabuvir; OMB, ombitasvir; PegIFN, pegylated interferon; PTV, paritaprevir; r, ritonavir; RBV, ribavirin; SOF, sofosbuvir; TPV, telaprevir.

* OMB/PTV/r + DSV ± RBV duration for cirrhosis is a weighted average of the duration for those with genotype 1b (indicated for 12 weeks) and the duration for those with genotype 1a (indicated for 24 weeks); the duration for the comparators did not vary by fibrosis level in their clinical trials.

† AbbVie trial publications—see Supplementary Appendix Table A3.

‡ Duration for direct-acting antiviral agents is the first figure, and duration for PegIFN/RBV is the second figure.

Table 5. Treatment-related costs for those with chronic genotype 1 hepatitis C virus infection.

Treatment-related cost	Base-case value		Source
Drug regimen cost per day
OMB/PTV/r + DSV	£416.67		MIMS^50
SOF	£416.43		′′
TPV	£266.64		′′
BOC	£100.00		′′
PegIFN	£19.84		′′
RBV	£10.58		′′
On-treatment monitoring costs
OMB/PTV/r + DSV ± RBV	£468 (no cirrhosis)	£790 (cirrhosis)	Based on Shepherd et al.^35 microcosting, but inflated to 2013 values using PSSRU inflation indices reported in Curtis^51
SOF + PegIFN/RBV	£468
TPV + PegIFN/RBV	£956 (naive)	£1072 (experienced)
PegIFN/RBV	£1072
BOC + PegIFN/RBV	£956
Treatment-related adverse event costs
Anemia	£482		Thorlund et al.^52
Rash	£160		′′
Depression	£398		′′
Grade 3 or 4 neutropenia	£942		NICE Sofosbuvir STA^53
Grade 3 or 4 thrombocytopenia	£841		′′

BOC, boceprevir; DSV, dasabuvir; MIMS, Monthly Index of Medical Specialities; NICE, National Institute for Health and Care Excellence; OMB, ombitasvir; PegIFN, pegylated interferon; PSSRU, Personal Social Services Research Unit; PTV, paritaprevir; r, ritonavir; RBV, ribavirin; SOF, sofosbuvir; STA, single technology assessment; TPV, telaprevir.

Figure 2. Base-case clinical outcomes for chronic genotype 1 hepatitis C virus infected, (a) treatment-naive patients and (b) treatment-experienced patients. BOC, boceprevir; CC, compensated cirrhosis; DCC, decompensated cirrhosis; DSV, dasabuvir; HCC, hepatocellular carcinoma; IFN, interferon; OMB, ombitasvir; PegIFN, pegylated interferon; PTV, paritaprevir; r, ritonavir; RBV, ribavirin; SOF, sofosbuvir; TPV, telaprevir.

Table 6. Base-case economic results for chronic genotype 1 hepatitis C virus infected, treatment-naïve, and treatment-experienced patients.

Regimen	Total costs, £	Total LYs	Total QALYs	ICER* vs PegIFN/RBV	ICER† incremental
Treatment naive
PegIFN/RBV	£22,872	19.68	13.72	n/a	n/a
BOC + PegIFN/RBV	£32,147	19.94	14.22	£18,366	Extendedly dominated
TPV + PegIFN/RBV	£35,887	20.16	14.55	£15,602	Extendedly dominated
SOF + PegIFN/RBV	£44,337	20.46	15.01	£16,618	Dominated
OMB/PTV/r + DSV ± RBV	£43,624	20.59	15.21	£13,864	£13,864
Treatment experienced
PegIFN/RBV	£30,128	17.13	11.07	n/a	n/a
TPV + PegIFN/RBV	£42,646	17.92	12.10	£12,095	Extendedly dominated
OMB/PTV/r + DSV ± RBV	£51,882	18.72	13.19	£10,258	£10,258

BOC, boceprevir; DSV, dasabuvir; ICER, incremental cost-effectiveness ratio; LY, life-year; n/a, not applicable; OMB, ombitasvir; PegIFN, pegylated interferon; PTV, paritaprevir; QALY, quality-adjusted life-year; r, ritonavir; RBV, ribavirin; SOF, sofosbuvir; TPV, telaprevir.

* ICER = incremental cost divided by incremental QALY for all regimens compared with PegIFN/RBV.

† ICER = incremental cost divided by incremental QALY for each regimen compared with the next most costly therapy; dominated = more costly and less effective; extended dominance = cost-effectiveness ratio is higher than that for a more effective therapy.

Figure 3. Tornado diagram: deterministic sensitivity analysis for (a) treatment-naive and (b) treatment-experienced patients with chronic genotype 1 hepatitis C infection: OMB/PTV/r + DSV ± RBV compared with pegIFN/RBV. CC, compensated cirrhosis; DCC, decompensated cirrhosis; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; OMB/PTV/r + DSV ± RBV, ombitasvir/paritaprevir/ritonavir and dasabuvir ± ribavirin; PegIFN/RBV, pegylated interferon + ribavirin; SVR, sustained virologic response.

Figure 4. Cost-effectiveness acceptability curves for (a) treatment-naive and (b) treatment-experienced patients with chronic genotype 1 hepatitis C infection. BOC, boceprevir; OMB/PTV/r + DSV ± RBV, ombitasvir/paritaprevir/ritonavir and dasabuvir ± ribavirin; PegIFN/RBV, pegylated interferon + ribavirin; SOF, sofosbuvir; TPV, telaprevir.

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