title: Overall safety profile of boceprevir plus peginterferon alfa-2b and ribavirin in patients with chronic hepatitis C genotype 1: a combined analysis of 3 phase 2/3 clinical trials.
abstract: OBJECTIVE
  Triple therapy with peginterferon/ribavirin (PR) plus an NS3 protease inhibitor has emerged as the standard-of-care for patients with chronic hepatitis C genotype-1. We provide a detailed safety analysis comparing PR to boceprevir plus PR (BOC/PR) across three phase 2/3 studies.
  
  
  METHODS
  SPRINT-1 was an open-label phase 2 study in 595 treatment-naive patients. In the two phase 3 studies, 1500 patients (1097 treatment-naive, SPRINT-2; 403 treatment-failure, RESPOND-2) were randomized to receive PR alone, or one of two regimens where BOC was added to PR after a 4-wk PR lead-in. In this analysis, the respective BOC/PR and PR arms were combined for all three trials. The benefit of shortened duration of treatment using response-guided therapy (RGT) was also explored in the SPRINT-2 trial.
  
  
  RESULTS
  Only two adverse events, anaemia and dysgeusia, occurred 20% more often with the BOC-containing regimens compared with PR. Nausea, diarrhoea and neutropenia were the only other common events with an incidence of at least 5% greater when BOC was added to the PR backbone. The proportions of patients reporting serious adverse events (AE), life-threatening AEs, and study drug discontinuation because of an AE were similar in the PR and BOC/PR arms. In treatment-naive patients, RGT generally did not result in a lower frequency of common AEs; however, RGT led to decreased exposure to all 3 study drugs and to a decrease in the mean duration of several clinically relevant AEs such as anaemia, neutropenia, fatigue and depression, as well as earlier normalization of haemoglobin and neutrophil counts.
  
  
  CONCLUSIONS
  The safety profile of BOC combination therapy largely reflects the known profile of peginterferon and ribavirin, with incremental haematolgical effects and dysgeusia. Shorter treatment duration with RGT significantly reduced the duration of AEs.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School (MHH), Hannover, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Jonathan
authors.initials: J
authors.lastname: McCone
authors.forename: Mitchell N
authors.initials: MN
authors.lastname: Davis
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Rossaro
authors.forename: Eugene
authors.initials: E
authors.lastname: Schiff
authors.forename: Mitchel L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Bruce
authors.initials: B
authors.lastname: Bacon
authors.forename: Marc
authors.initials: M
authors.lastname: Bourliere
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
authors.forename: Savino
authors.initials: S
authors.lastname: Bruno
authors.forename: Luis
authors.initials: L
authors.lastname: Balart
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
authors.forename: Paul
authors.initials: P
authors.lastname: Kwo
authors.forename: Fred
authors.initials: F
authors.lastname: Poordad
authors.forename: Franco
authors.initials: F
authors.lastname: Felizarta
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
authors.forename: Frans A
authors.initials: FA
authors.lastname: Helmond
authors.forename: Heather L
authors.initials: HL
authors.lastname: Sings
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Pedicone
authors.forename: Margaret
authors.initials: M
authors.lastname: Burroughs
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Brass
authors.forename: Janice K
authors.initials: JK
authors.lastname: Albrecht
authors.forename: John M
authors.initials: JM
authors.lastname: Vierling
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects*; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives*; D011994:Recombinant Proteins / Q000009:adverse effects; D012254:Ribavirin / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; 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; C417083:peginterferon alfa-2b
keywords: Victrelis; antiviral therapy