title: Benefit of Treatment Individualization in Patients with Chronic Hepatitis C Receiving Peginterferon Alfa-2a and Ribavirin in a Large Noninterventional Cohort Study.
abstract: OBJECTIVE
  Individualization of treatment with peginterferon alfa and ribavirin in patients with chronic hepatitis C showed benefit in controlled trials and was implemented in treatment guidelines to increase response rates and to reduce side effects and costs. However, it is unknown whether individualization was adopted in routine daily practice and whether it translated into improved outcomes.
  
  
  METHODS
  From a large noninterventional cohort study, clinical and virologic response data of 10,262 HCV patients who received peginterferon alfa-2a and ribavirin between 2003-2007 and 2008-2011 were analyzed. To account for treatment individualization, a matched-pair analysis (2,997 matched pairs) was performed. Variation in treatment duration and dosing of ribavirin were analyzed as indicators for individualization.
  
  
  RESULTS
  Sustained virological response (SVR) rates were similar between 2003-2007 and 2008-2011 (62.0% vs. 63.7%). Patients with comorbidities were more abundant in the later period, (44.3% vs. 57.1%). The subsequent matched-pair analysis demonstrated higher SVR rates in the 2008-2011 period (64.3%) than in the 2003-2007 period (61.2%, p=0.008). More patients received abbreviated or extended treatment regimens in the later than the earlier period as an indicator of treatment individualization. To the same end, ribavirin doses were higher in the later period (12.6 versus 11.6 mg/kg/day). Factors independently associated with SVR included HCV genotype, low baseline viral load, younger age, route of infection, absence of concomitant diseases, lower APRI score, normal gamma-GT, higher ribavirin doses, no substitution for drug abuse, treatment duration, and treatment in the 2008-2011 period.
  
  
  CONCLUSIONS
  Treatment individualization with peginterferon alfa and ribavirin was implemented in daily routine between 2003-2007 and 2008-2011, SVR rates improved in the same period. These findings may be most relevant in resource-limited settings.
authors.affiliation: Practice of Gastroenterology, Berlin, Germany.
authors.forename: Wolf Peter
authors.initials: WP
authors.lastname: Hofmann
authors.affiliation: Center for HIV and Hepatogastroenterology, Düsseldorf, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Mauss
authors.affiliation: Infektiologikum, Frankfurt, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lutz
authors.affiliation: Practice of Hepatology, Göttingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schober
authors.affiliation: Practice of Hepatology, Hannover, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Böker
authors.affiliation: Practice of Gastroenterology, Kassel, Germany.
authors.forename: Gero
authors.initials: G
authors.lastname: Moog
authors.affiliation: Center of Infectious Diseases, Berlin, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Baumgarten
authors.affiliation: Institute for Clinical Research and Statistics, Offenbach, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Pfeiffer-Vornkahl
authors.affiliation: Virology, Roche Pharma AG, Grenzach-Wyhlen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Alshuth
authors.affiliation: Center of Gastroenterology, Herne, Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Hüppe
authors.affiliation: Department of Gastroenterology, Hepatology, and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.affiliation: Department of Gastroenterology, Hepatology, and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.affiliation: Dept. of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.
authors.forename: Eckart
authors.initials: E
authors.lastname: Schott
mesh_terms: D000328:Adult; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a