DIRECT ANTIVIRAL DRUGS FOR THE TREATMENT OF CHRONIC HEPATITIS C PATIENTS WITH GENOTYPE 1 OR 4 IN FRANCE - COST-EFFECTIVENESS OF OMBITASVIR/PARITAPREVIR/RITONAVIR WITH OR WITHOUT DASABUVIR BY FIBROSIS SUBGROUP

Purpose: Particularly in the era of highly-effective but costly direct acting antivirals (DAAs) the treatment of patients with mild chronic hepatitis C (CHC) is still debated. We evaluated long-term health economic outcomes of different antiviral treatments including ombitasvir/paritaprevir/ritonavir±dasabuvir (OBV/PTV/r±DSV) for CHC patients infected with genotype (GT) 1 or 4 in France based on their fibrosis stages.

Method(s): A Markov-cohort simulation model for the French health-care context was developed and applied to evaluate different antiviral treatment regimens: peginterferon+ribavirin (P+R), telaprevir+P+R (TVR+PR), boceprevir+P+R (BOC+P+R), sofosbuvir+P+R (SOF+P+R), simeprevir+P+R (SIM+P+R), SOF+R, SOF+SIM, SOF+daclatasvir±R (SOF+DAC±R), SOF+ledipasvir±R (SOF+LDV±R), OBV/PTV/r±DSV±R. Progression rates were retrieved from published observational studies. Antiviral treatment was based on European and French treatment guidelines. We used international clinical trial data for SVR, adverse events, discontinuation and change in treatment-related quality-of-life (QoL). French data on population characteristics, disease-related QoL, and costs (index year 2014/15) were taken from published literature, databases and original studies. We adopted the collective payers’ perspective with 4% annual discount rate for costs and effects. Separate analyses were performed for different fibrosis stages (mild, moderate, cirrhosis) considering specific population characteristics in these groups. Outcomes included lifetime costs, life years (LY), quality-adjusted life years (QALY), and the incremental cost-effectiveness ratio (ICER). Comprehensive sensitivity analyses were performed.

Result(s): New DAAs achieved highest effectiveness. Among the most effective therapies, OBV/PTV/r+DSV±R achieved lowest ICERs, falling below 51,000 Euro/QALY in GT1 treatment-naïve patients across all fibrosis subgroups and below 22,500 Euro/QALY in treatment-experienced mild to moderate CHC patients.  ICER in treatment-experienced patients with cirrhosis was higher. In GT4 treatment-naïve and -experienced mild to moderate CHC patients, OBV/PTV/r+R again achieved lowest ICERs (< 37,000 Euro/QALY) among the most effective DAAs. Cirrhotic GT4 patients were not evaluated in the analyses. Regimens achieving very small additional effects versus OBV/PTV/r+DSV±R had high ICERs making them unlikely to be cost-effective. In sensitivity analyses, the most influential parameters were the SVRs of different regimens, discount rate, progression to advanced disease and the disutility for being viral-positive.

Conclusion(s): Based on our analyses, ICERs of different DAAs vary substantially across fibrosis subgroups. The informed selection of optimal DAA medication for each fibrosis subgroup is crucial and the optimal choice depends on the willingness-to-pay in France. Across all fibrosis subgroups there are cost-effective choices of DAA regimens including OBV/PTV/r+DSV±R.