WHEN AND WHERE IN THE TREATMENT PATHWAY IS IT APPROPRIATE TO USE NEW DIRECT ACTING ANTIVIRALS FOR CHRONIC HEPATITIS C?

Purpose:

To provide a complete assessment of the cost-effective treatment pathway for patients with hepatitis C virus (HCV) infection with advanced fibrosis.

Method(s):

We include three important features of the decision problem ignored in previous economic evaluations internationally. (1) Retreatment if patients do not achieve cure, by comparing all licensed drugs in sequences of one to three lines. (2) Inclusion of watchful waiting followed by treatment at cirrhosis as a relevant comparator. (3) Allowing patients to be treated at more severe disease stages for patients who do not achieve cure with the initial treatment sequence.

We developed a decision-analytic Markov model to estimate lifetime costs and health benefits of all comparators and compared treatment strategies in subgroups defined by viral genotype, prior treatment experience and interferon eligibility. Value of information analysis explored in which patient subgroups it would be most useful to conduct future research. Additionally, we have prepared a tool to recalculate the cost-effective strategies for a given set of prices and thresholds since some health care systems have negotiated discounts.

Result(s):

In contrast to previous analyses, and given the current list prices, eligible patients with genotypes 2-4 should be initially offered peginterferon with ribavirin rather than the newer drugs. First-line treatment with sofosbuvir-ledipasvir over 8 weeks is cost-effective in HCV genotype 1 patients. The cost-effective strategies all include multiple lines of therapy prior to cirrhosis (where available), resulting in cure rates of 89%-98% across HCV genotypes. Future research is most valuable in HCV genotypes 3 and 4, with an upper bound of £3 million. The tool can help clinicians and health care systems locally and worldwide decide on the cost-effective strategy given their local context and prices.

Conclusion(s):

Health systems should invest in sequential therapy with multiple lines to treat HCV patients with advanced fibrosis. Although current guidance permits first line treatment with the new drugs, we concluded that their use should mostly be reserved to patients who do not achieve cure from first line treatment with peginterferon. This work demonstrates that excluding sequential therapy as a relevant comparator will bias results and ultimately have a detrimental impact to population health.  The tool shows how complex economic modelling can be made accessible and adaptable to policy-makers and clinicians needs.