Younger patients with advanced liver disease caused by hepatitis C should be prioritised for treatment with newly licensed directly acting antivirals to achieve the biggest reductions in ill health and hospitalisation, according to a modelling exercise presented by University of Pittsburgh researchers at the 63rd annual meeting of the American Association for the Study of Liver Diseases (AASLD) earlier this month in Boston.
According to Jagpreet Chhatwal of the University of Pittsburgh, many people who had deferred antiviral treatment for hepatitis C with pegylated interferon plus ribavirin started to request treatment for chronic hepatitis C when telaprevir and boceprevir, the first DAAs (oral directly acting agents), were approved and marketed a little over one year ago.
This increase in the numbers of people willing to be treated resulted in waiting lists, because of a limit on the number of people who could initiate treatment every week. Such waiting lists can be expected again in the future when next-generation DAAs are approved.
Current guidelines in Europe recommend therapy for all patients with compensated advanced liver disease (fibrosis stages F4 and F3), and the European Association for the Study of the Liver (EASL) says that therapy should be strongly considered in people with moderate liver fibrosis (stage F2). The American Association for the Study of Liver Diseases says that it will address the question of which patients should be prioritised for treatment in a 2013 revision of its guidelines on HCV treatment.
Chhatwal’s study goal was to develop an algorithm for prioritising patients for treatment on the basis of clinical need, using an assessment of the quality-adjusted life-years (QALYs) gained for different categories of patient according to whether treatment was started immediately or deferred for one year.
The model projected the number of years of good health that could be expected as a result of deferring or preventing decompensated cirrhosis, hepatocellular carcinoma, liver transplant and liver-related death per 1000 patients.
The model used efficacy data from the registration trials of telaprevir (Incivo or Incivek) and boceprevir (Victrelis) – the ADVANCE, REALIZE, SPRINT-2 and RESPOND-2 trials – and estimated progression rates of hepatitis C disease from previously published studies, to simulate the effects of these two strategies.
The researchers evaluated the impact of waiting for treatment by fibrosis stage, previous treatment response, the IL-28B polymorphism, age, and sex.
Those who need treatment most urgently will be those with the most advanced METAVIR score (which measures the degree of liver damage).
In a 50-year-old cirrhotic person, the projected gain in QALYs due to immediate access to treatment when compared to receiving treatment after 1 year was 0.54 (treatment-naive), 0.71 (previous relapser), 0.51 (partial responder) and 0.27 (previous null responder). (These values refer to fractions of one year.) The corresponding reductions in the incidence of decompensated cirrhosis, hepatocellular carcinoma, liver transplant and liver-related death per 1000 patients were between 10-24, 12-31, 2-5 and 17-44 cases per thousand, respectively.
The gains in QALYs due to immediate treatment in people with cirrhosis, based on IL-28B genotype, were between 0.52-0.76 (highest in people with the CC sub-genotype, those who respond best to interferon-based treatment). For people with a score of F4 (cirrhosis), the corresponding loss in QALYs of waiting one year is 28 weeks.
The gain in QALYs in F0-F3 patients by immediate treatment was significantly lower (0.04-0.07 QALYs). The loss in QALYs would be very low in people with scores of F0-F3: four weeks in people with an F3 score, and three weeks in those with scores of F0-F2.
All other factors being equal, the gain in QALYs in younger people was higher than that in older people, Chhatwal said.
Among previously treated patients, prioritisation of previous relapsers over previous partial responders and previous null responders would achieve greater gains in QALYs owing to the higher likelihood of sustained virologic response in these patients.
Their recommended prioritisation order (from highest to lowest) by patient characteristics is:
- Cirrhosis
- [a] younger age,
- [b] prior relapser,
- [c] treatment naive or previous partial responder,
- [d] IL-28B genotype CC,
- [e] others),
- (2) METAVIR score F3
- [a] younger age,
- [b] others, and
- (3) METAVIR score F0–F2.
The authors say that their modelling exercise provides a needs-based prioritisation score of patients that they call “clinically intuitive”, which will “maximize the value of DAAs to society”.
Chhatwal J et al. Prioritization of hepatitis C patients for treatment with direct acting antiviral agents. The 63rd Annual Meeting of the American Association for the Study of Liver Diseases, Boston, parallel session 22, abstract 152, 2012.