title: Optimizing choice of oral interferon-free treatment for genotype 1 hepatitis C virus using testing for NS5A resistance: a cost-utility analysis from the perspective of the Italian National Health Service.
abstract: BACKGROUND
  Patients with genotype-1 hepatitis C virus infection who have failed to respond to standard therapy or who relapse following treatment may be considered for an interferon-free regimen incorporating a nonstructural protein 5A (NS5A) inhibitor. Sustained virologic response (SVR) with these regimens is typically >90%, but this is reduced in patients with NS5A resistance. European Association for Study of the Liver guidelines recommend simeprevir + sofosbuvir ± ribavirin (SMV+SOF±R) for re-treating patients failing an NS5A inhibitor-containing regimen. An alternative strategy would be to test for NS5A resistance prior to treatment, with therapy optimized based on the results. This study investigates the cost-effectiveness of this strategy.
  
  
  METHODS
  A Markov model was used to estimate disease progression for treatment-experienced genotype 1 patients with severe fibrosis or compensated cirrhosis. Targeted treatment with either SMV+SOF±R or sofosbuvir + ledipasvir ± ribavirin (SOF+LDV±R) based on pretreatment NS5A resistance testing was compared to routine SOF+LDV±R without testing. Treatment duration was 12 or 24 weeks for patients with severe fibrosis or compensated cirrhosis (Metavir F3/F4). SVR data for the treatment options were based on the results of published clinical trials. The analysis was carried out from the perspective of the Italian National Health Service.
  
  
  RESULTS
  Optimized treatment using NS5A resistance testing yielded 0.163 additional QALYs and increased costs of €2,789 per patient versus no testing. The incremental cost-effectiveness ratio (ICER) was €17,078/QALY. Sensitivity analysis identified the SVR attributable to each of the treatment regimens as the most sensitive determinant of ICER (range: €10,055/QALY-€43,501/QALY across plausible range). Probabilistic sensitivity analysis demonstrated that, at a willingness-to-pay threshold of €30,000/QALY, the probability that NS5A-directed treatment will be cost-effective is 81.4%.
  
  
  CONCLUSIONS
  Optimizing therapy with either SMV+SOF±R or SOF+LDV±R based on pretreatment NS5A resistance testing was cost-effective from the perspective of the Italian National Health Service, in treatment-experienced patients with severe fibrosis or compensated cirrhosis.
authors.affiliation: Pharmerit BV, Marten Meesweg, Rotterdam, the Netherlands.
authors.forename: Kirsten Y
authors.initials: KY
authors.lastname: Westerhout
authors.affiliation: Pharmerit BV, Marten Meesweg, Rotterdam, the Netherlands.
authors.forename: Walter
authors.initials: W
authors.lastname: Bouwmeester
authors.affiliation: Janssen EMEA, Turnhoutseweg, Beerse, Belgium.
authors.forename: Inge
authors.initials: I
authors.lastname: Duchesne
authors.affiliation: Janssen EMEA, Turnhoutseweg, Beerse, Belgium.
authors.forename: Marta
authors.initials: M
authors.lastname: Pisini
authors.affiliation: Pharmerit BV, Marten Meesweg, Rotterdam, the Netherlands.
authors.forename: Marjanne A
authors.initials: MA
authors.lastname: Piena
authors.affiliation: Janssen-Cilag SpA, Via Michelangelo Buonarroti, Cologno Monzese, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Damele
authors.affiliation: Janssen EMEA, Turnhoutseweg, Beerse, Belgium.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Gueron
authors.affiliation: Pharmerit BV, Marten Meesweg, Rotterdam, the Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Treur
authors.affiliation: JB Medical Ltd, Old Brickworks, Little Cornard, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Belsey
keywords: NS5A inhibitor; health economics; hepatitis C; ledipasvir; simeprevir; sofosbuvir