Modelling the Relationship
Between Sustained Virologic Response and Treatment Uptake
Rate on Future Prevalence and Incidence of Hepatitis C in the UK
Hayley Bennett1, 2, Phil McEwan1, 2, Tom Ward1, 2, Anupama Kalsekar3 and Yong Yuan3
1 HEOR
Ltd, Monmouth, Wales, UK 2 School of Human & Health Sciences, Swansea University, Wales, UK
3 Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ
Poster no.
PIN106
Figure 2: Modelled prevalence of chronic HCV amongst PWIDs at the end of
2027 as a function of SVR rate achieved and maximum rate of treatment uptake
Introduction
The prevalence of hepatitis C remains high amongst people who inject
drugs (PWID). Globally, approximately 90% of newly acquired hepatitis
C virus (HCV) infections are attributed to injecting drug use, although
this percentage varies by country [1, 2].
Modelling studies have demonstrated that modest rates of HCV
treatment among active PWID could effectively reduce future disease
transmission, resulting in a reduction of overall HCV prevalence [3].
The emergence of novel treatments capable of achieving sustained
virologic response (SVR) rates approaching 100% mean that
pharmacological intervention has real potential to alter the future
transmission dynamics of the disease [4].
This study aims to quantify the value of treatment amongst PWID, with
new direct acting antivirals (DAAs) and at increased uptake rates, with
respect to the avoidance of future infections and subsequent long-term
complications of HCV in the UK.
Methods
Figure 3: Cost savings and quality-adjusted life year gains made as a result of
avoiding future complications of new chronic HCV infections
A dynamic HCV transmission and disease progression model was
developed, incorporating acute and chronic infection, and long-term
complications (decompensated cirrhosis, cancer, liver transplant and
mortality), with the potential for reinfection following treatment
failure. (Figure 1)
The model was populated with UK prevalence and therapy data [3].
Table 1 summarises the key model inputs. Future costs, life years and
quality adjusted life years (QALYs) were discounted at 3.5%.
No treatment was assumed prior to 2002, as no therapies were
approved by NICE at the time, followed by a linear scale-up in
treatment uptake to the baseline rate of 8 per 1,000 PWID per year in
2007. This fixed annual number of treatments was assumed to be
constant until 2015. From 2015 to 2017, the treatment rate was scaledup linearly to annual uptake rates of 10-250 per 1,000 PWID.
All treatment was assumed to be a combination of pegylated interferon
and ribavirin (PEG-IFN+RBV) prior to 2012. After 2012, 50% of HCV
genotype 1 individuals were assumed to receive telaprevir or
boceprevir triple therapy. From 2015, the introduction of a new
treatment was modelled for all treated individuals.
Scenarios of current treatment efficacy and uptake were compared to
future SVR rates of 90-100% and increased uptake over varied
horizons.
Figure 1: Disease transmission and treatment model schematic
Results
Long-term modelling suggests that current uptake rates and treatments
would lead to modest reductions in the number of HCV infections, with
prevalence still exceeding 5% after 200 years. New treatments
achieving 90% SVR could reduce prevalence below 5% within 60 years
at current uptake rates, or within 5 years if all patients were treated.
Figure 2 illustrates the relationship between SVR and treatment uptake
over the period 2015-2027 in terms of future prevalence. The rate of
treatment uptake was the key driver of reductions in future prevalence.
Amongst 4,240 PWID, the avoidance of 20-580 future chronic HCV
infections is expected over the period 2015-2027 with current SVR
rates, based on the upper and lower rates of increased uptake modelled.
With 90% SVR, future infections avoided ranged from 34-912 over the
same period as a result of increasing treatment uptake.
Figure 3 presents the estimated cost savings and QALY gains associated
with the avoidance of future complications of new chronic HCV
infections, which may be prevented as a result of increased treatment
uptake among PWID.
Table 1: Summary of key modelling data inputs taken from Martin et al 2013 [2]
Duration
% SVR
Parameter
PWID population size
Overall mortality rate
Proportion genotype 1
Chronic HCV prevalence among PWID in 2012
Proportion spontaneous clearance of acute infection
Duration acute infection period
Baseline annual treatment rate
PEG-IFN+RBV - genotype 1
PEG-IFN+RBV - genotype 2/3
Telaprevir/boceprevir - genotype 1
IFN-free DAAs
PEG-IFN+RBV - genotype 1 (SVR/non SVR)
PEG-IFN+RBV - genotype 2/3
Telaprevir/boceprevir - genotype 1
IFN-free DAAs
Value
4,240
1% per year
53%
25%
26%
6 months
8 per 1,000 PWID
37%
67%
63%
90%
48/12 weeks
24 weeks
24 weeks
12 weeks
With 90% SVR, the reduction in downstream HCV infections associated
with increased treatment uptake resulted in approximate discounted
gains of up to 300 life-years (from avoiding reduced life expectancy
from HCV infection) and 1,700 QALYs (from avoiding the disutility of
HCV infection and related complications). Associated discounted cost
savings were estimated at up to £5.4 million.
Conclusions
Increased treatment among PWID with more effective therapies could
change the future dynamics, cost and health burden of HCV-related
disease significantly.
While improved SVR profiles led to reductions in modelled prevalence,
increased treatment uptake was the key driver of future infections
avoided. Whether the scale-up required to eradicate disease is both
affordable and achievable is an important challenge for both clinicians
and public health policy makers to address.
1. Hellard, M., R. Sacks-Davis, and J. Gold, Hepatitis C treatment for injection drug users: a review of the available evidence. Clinical Infectious Diseases, 2009. 49(4): p. 561-573.
2. Martin, N.K., et al., Hepatitis C virus treatment for prevention among people who inject drugs: Modeling treatment scale-up in the age of direct-acting antivirals. Hepatology, 2013. 58(5): p. 1598-1609.
3. Martin, N.K., et al., Can antiviral therapy for hepatitis C reduce the prevalence of HCV among injecting drug user populations? A modeling analysis of its prevention utility. Journal of hepatology, 2011.
54(6): p. 1137-1144.
4. Dore, G.J., The changing therapeutic landscape for hepatitis C. Med J Aust, 2012. 196: p. 629-632.
This study was funded by an unrestricted grant from Bristol-Myers Squibb
Pharmaceuticals Ltd.
Presented at ISPOR 17th Annual European Congress, 8-12 November 2014, Amsterdam, The Netherlands