title: Predicting early and sustained virological responses in prior nonresponders to pegylated interferon alpha-2b plus ribavirin retreated with peginterferon alpha-2a plus ribavirin and the benefit-risk ratio of retreatment.
abstract: OBJECTIVE
  To evaluate the predictive value of complete early virological response (cEVR) on sustained virological response (SVR) following retreatment with peginterferon alpha-2a (40 kDa) plus ribavirin in previous nonresponders to peginterferon alpha-2b (12 kDa).
  
  
  BACKGROUND
  In the randomized multinational retreatment with Pegasys in patients not responding to PegIntron therapy study, a 72-week regimen of peginterferon alpha-2a (40 kDa) plus ribavirin improved SVR rates over a standard 48-week regimen in previous nonresponders to peginterferon alpha-2b (12 kDa). cEVR, defined as hepatitis C virus RNA <50 IU/mL at treatment week 12, was an important predictor of SVR.
  
  
  METHODS
  We conducted an exploratory analysis of the retreatment with Pegasys in patients not responding to PegIntron therapy study data to better define the predictive value of cEVR for SVR in this patient population.
  
  
  RESULTS
  In total, 157 of the 942 patients achieved a cEVR (16.7%). SVR rates were higher with 72 versus 48 weeks of retreatment in patients with a cEVR (57% vs. 35%), whereas SVR rates were <5% in patients without cEVR in both groups. The relative adverse event (AE) burden was lower with 72 weeks of treatment (8.1 vs. 10.1 AEs/y of treatment) as was the estimated number of AEs per SVR achieved (55 vs. 100). Cumulative treatment duration required to achieve 1 SVR was lower with 72 weeks of treatment (6.7 vs. 10.0 y/SVR) and lower still assuming that treatment was stopped at week 12 for non-cEVR patients (3.6 vs. 7.1 y/SVR).
  
  
  CONCLUSIONS
  cEVR is a reliable predictor of SVR in patients retreated with peginterferon alpha-2a (40 kDa) plus ribavirin. Seventy-two-week retreatment has a more favorable benefit-risk ratio than 48 weeks, especially when cEVR is used to identify patients most likely to be cured.
authors: *Hôpital Beaujon, Boulevard du Général Leclerc, Clichy, France †Instituto Di Clinica Medica Policlinico, Palermo ∥Department of Clinical Medicine, University of Bologna, Bologna, BO, Italy ‡Internal Medicine Department, Hepatology Division, Gaffrèe e Güinle University Hospital, College of Medicine & Surgery, University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil §Department of Internal Medicine, Saint Louis University School of Medicine, St Louis ¶Kansas City Gastroenterology and Hepatology, LLC, Kansas City, MO #Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA **Hospital La Paz de Madrid, Madrid, Spain ††Interdisziplinäres Facharztzentrum Sachsenhausen, MVZ-Sachsenhausen, Frankfurt ‡‡IST GmbH, Mannheim, Germany §§Roche Products Ltd, Welwyn, UK ∥∥F. Hoffmann-La Roche Ltd, Basel, Switzerland ¶¶Center for Liver Diseases, University of Chicago Hospitals, Chicago, IL.
authors: Patrick
authors: P
authors: Marcellin
authors: Antonio
authors: A
authors: Craxi
authors: Carlos E
authors: CE
authors: Brandao-Mello
authors: Adrian M
authors: AM
authors: Di Bisceglie
authors: Pietro
authors: P
authors: Andreone
authors: Bradley
authors: B
authors: Freilich
authors: K
authors: K
authors: Rajender Reddy
authors: Antonio
authors: A
authors: Olveira Martín
authors: Gerlinde
authors: G
authors: Teuber
authors: Diethelm
authors: D
authors: Messinger
authors: Greg
authors: G
authors: Hooper
authors: Cynthia
authors: C
authors: Wat
authors: Fernando
authors: F
authors: Tatsch
authors: Donald M
authors: DM
authors: Jensen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D019233:Retreatment; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a