1. J Clin Gastroenterol. 2013 Feb 24. [Epub ahead of print]

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.

Marcellin P, Craxi A, Brandao-Mello CE, Di Bisceglie AM, Andreone P, Freilich B, 
Rajender Reddy K, Olveira Martín A, Teuber G, Messinger D, Hooper G, Wat C,
Tatsch F, Jensen DM.

*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.

GOALS:: 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. STUDY:: 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.

PMID: 23442834  [PubMed - as supplied by publisher]