title: Comparative effectiveness of the hepatitis C virus protease inhibitors boceprevir and telaprevir in a large U.S. cohort.
abstract: BACKGROUND
  Limited data exist on the effectiveness of boceprevir and telaprevir in routine practice.
  
  
  OBJECTIVE
  To assess the comparative effectiveness of boceprevir and telaprevir regimens.
  
  
  METHODS
  In this observational, intent-to-treat cohort analysis of hepatitis C genotype 1-infected veterans initiated on peginterferon/ribavirin and boceprevir (n = 661) or telaprevir (n = 198), we determined sustained virological response (SVR), treatment discontinuation rates and adverse haematological events. Inverse probability-of-treatment weighting (IPTW) was used to estimate the effect of one drug over the other, with matched pairs and unweighted logistic regression on the entire cohort for comparison.
  
  
  RESULTS
  Of 835 veterans, SVR occurred in 50% and 52% receiving boceprevir- and telaprevir-based treatment, respectively (P = 0.72). No significant differences occurred among subgroups: cirrhotics (37% vs. 39%, P = 0.94), null responders (23% vs. 18%, P = 0.81), partial responders (39% vs. 58%, P = 0.15) and relapsers (60% vs. 77%, P = 0.11). Early discontinuation rates for boceprevir and telaprevir, respectively, were 31% and 28% by week 24 (P = 0.46) and 54% and 45% by 48 weeks (in those completing at least 28 weeks) (P = 0.14). Choice of telaprevir over boceprevir was significantly associated with SVR in multivariate models (IPTW OR: 1.57, 95% CI: 1.10-2.25, P = 0.01; matched-pairs OR: 1.91, 95% CI: 1.23-3.00, P = 0.004; unweighted OR: 1.50 95% CI: 1.05-2.14, P = 0.02). Rates of haematological adverse events in boceprevir- and telaprevir-treated patients were as follows: anaemia 59% vs. 51%, P = 0.30, thrombocytopenia 41% vs. 48%, P = 0.26, neutropenia 41% vs. 27%, P = 0.04.
  
  
  CONCLUSIONS
  Sustained virological response was more likely with telaprevir-based regimens compared with boceprevir-based regimens in routine medical practice, after accounting for patient differences. Early discontinuation and haematological events, however, were similar.
authors.affiliation: Office of Public Health/Population Health Program, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA; Department of Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
authors.forename: L I
authors.initials: LI
authors.lastname: Backus
authors.forename: P S
authors.initials: PS
authors.lastname: Belperio
authors.forename: T A
authors.initials: TA
authors.lastname: Shahoumian
authors.forename: R
authors.initials: R
authors.lastname: Cheung
authors.forename: L A
authors.initials: LA
authors.lastname: Mole
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D057186:Comparative Effectiveness Research; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced; D014481:United States / Q000453:epidemiology; D014728:Veterans
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011480:Protease Inhibitors; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline