International, multicenter, randomized, controlled study comparing dynamically individualized versus standard treatment in patients with chronic hepatitis C.
OBJECTIVE
The aim of this study was to increase virologic response rates by individualized treatment according to the early virologic response.


METHODS
Serum HCV-RNA was frequently quantified in patients with chronic hepatitis C (n=270) treated with peginterferon alfa-2a (180 microg/week) and ribavirin (1000-1200 mg/day). After 6 weeks patients were classified as rapid (RVR), slow (SPR), flat (FPR), or null responders (NUR) and randomized within each viral kinetic class to continue therapy either with an individualized or standard regimen. Individualized therapy comprised peginterferon monotherapy (48 weeks) or shorter combination therapy (24 weeks) for RVR, triple therapy with histamine (1 mg/day) (48 weeks) or prolonged combination therapy (72 weeks) for SPR, triple therapy for FPR, and high-dose peginterferon (360 microg/week) plus ribavirin for NUR patients.


RESULTS
Patients were categorized as RVR (n=171), SPR (n=65), FPR (n=10), or NUR (n=22). Overall end-of-treatment and sustained virologic response rates were 77 and 60% in the individualized and 77 and 66% in the standard treatment arm, respectively. Histamine in addition to peginterferon and ribavirin and high-dose peginterferon plus ribavirin did not improve virologic response rates in patients with FPR and NUR, respectively.


CONCLUSIONS
An improvement in virologic efficacy was not achieved with the available individualized treatment options.
Zeuzem
Stefan
S
Saarland University Hospital, Homburg/Saar, Germany. Zeuzem@uniklinik-saarland.de
Pawlotsky
Jean-Michel
JM
Lukasiewicz
Esther
E
von Wagner
Michael
M
Goulis
Ioannis
I
Lurie
Yoav
Y
Gianfranco
Elia
E
Vrolijk
Jan-Maarten
JM
Esteban
Juan I
JI
Hezode
Christophe
C
Lagging
Martin
M
Negro
Francesco
F
Soulier
Alexandre
A
Verheij-Hart
Elke
E
Hansen
Bettina
B
Tal
Ronen
R
Ferrari
Carlo
C
Schalm
Solko W
SW
Neumann
Avidan U
AU
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood / Q000187:drug effects / Q000235:genetics*; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D012449:Safety; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D004337:Drug Carriers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a