title: Early virologic responses and hematologic safety of direct-acting antiviral therapies in veterans with chronic hepatitis C.
abstract: OBJECTIVE
  There are limited data on the early effectiveness of direct-acting antiviral (DAA) therapies for patients with hepatitis C virus (HCV) infection in routine medical practice. We aimed to evaluate real-world experience with DAA-based regimens.
  
  
  METHODS
  By using the Veterans Affairs' Clinical Case Registry, we conducted a prospective observational intent-to-treat analysis of veterans infected with HCV genotype 1 who began treatment with pegylated interferon, ribavirin, and boceprevir (BOC, n = 661) or telaprevir (TVR, n = 198) before January 2012. We determined rates of virologic response at treatment weeks 4, 8, 12, and 24; futility; early discontinuation; and adverse hematologic events.
  
  
  RESULTS
  About one third of patients discontinued treatment by week 24 (30% BOC, 34% TVR). A higher percentage of treatment-naive, noncirrhotic patients receiving BOC had undetectable levels of virus at week 24 than patients receiving TVR (74% vs 60%; P = .03). There were no significant differences in rates of early response within subgroups of cirrhotic patients, prior relapsers, prior partial responders, or prior null responders. By week 24, treatment was determined to be futile for 14% of patients receiving BOC and 17% of those receiving TVR. No differences were observed in overall rates of anemia (50% BOC, 49% TVR) or thrombocytopenia (16% BOC, 18% TVR); higher rates of neutropenia were observed in BOC-treated patients (34% BOC, 21% TVR; P = .008).
  
  
  CONCLUSIONS
  HCV-infected veterans treated in routine medical practice with DAA-based regimens (BOC or TVR) had rates of early response comparable with those reported in clinical trials. However, they had higher rates of futility and early discontinuation than clinical trial participants. Further studies are needed to determine rates of sustained viral response.
authors.affiliation: Population Health Program/Office of Public Health, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA.
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Belperio
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Hwang
authors.forename: I Chun
authors.initials: IC
authors.lastname: Thomas
authors.forename: Larry A
authors.initials: LA
authors.lastname: Mole
authors.forename: Ramsey C
authors.initials: RC
authors.lastname: Cheung
authors.forename: Lisa I
authors.initials: LI
authors.lastname: Backus
mesh_terms: D000368:Aged; D000740:Anemia / Q000139:chemically induced*; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D011446:Prospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D014728:Veterans; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D009842:Oligopeptides; 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; D007372:Interferons; D011392:Proline
keywords: APRI; BOC; Cirrhosis; DAA; HCV; ICD-9; International Classification of Diseases, 9th revision; OR; PEG; Protease Inhibitor; RBV; SVR; TVR; Therapy; VA; Veterans Affairs; aspartate aminotransferase/platelet ratio index; boceprevir; direct-acting antiviral; hepatitis C virus; odds ratio; pegylated interferon; ribavirin; sustained virologic response; telaprevir