Re-treatment of patients with chronic hepatitis C who do not respond to peginterferon-alpha2b: a randomized trial.
BACKGROUND
Many patients with chronic hepatitis C have not responded to therapy with pegylated interferon plus ribavirin.


OBJECTIVE
To evaluate use of peginterferon-alpha2a plus ribavirin to re-treat nonresponders to peginterferon-alpha2b plus ribavirin.


METHODS
Randomized, parallel-group trial conducted between September 2003 and February 2007. Patients and researchers were not blinded to intervention assignment. Random assignment was centralized, computer-generated, and stratified by geographic region, hepatitis C virus (HCV) genotype, and histologic diagnosis.


METHODS
106 international centers.


METHODS
950 nonresponders to 12 or more weeks of therapy with peginterferon-alpha2b plus ribavirin.


METHODS
Peginterferon-alpha2a, 360 microg/wk, for 12 weeks, then 180 microg/wk to complete 72 weeks (group A) or 48 weeks (group B), or peginterferon-alpha2a, 180 microg/wk for 72 weeks (group C) or 48 weeks (group D). All patients received ribavirin, 1000 or 1200 mg/d.


METHODS
Sustained virologic response (SVR), defined as undetectable (<50 IU/mL) HCV RNA levels 24 weeks after the end of treatment.


RESULTS
The SVR rates in groups A (n = 317), B (n = 156), C (n = 156), and D (n = 313) were 16%, 7%, 14%, and 9%, respectively (relative risk [RR] for group A vs. group D [the primary comparison], 1.80 [95% CI, 1.17 to 2.77]; P = 0.006). Extended treatment duration increased SVR rates (16% for 72 weeks [groups A and C] vs. 8% for 48 weeks [groups B and D]; RR, 2.00 [CI, 1.32 to 3.02]; P < 0.001). Complete viral suppression (HCV RNA level <50 IU/mL)at week 12 was achieved in 21% of patients in groups A and B and 13% of those in groups C and D. Rates of SVR were 49% (77 of 157 patients) and 4% (32 of 719 patients) among those with and without complete viral suppression at week 12, respectively.


CONCLUSIONS
Nonresponders to peginterferon-alpha2a plus ribavirin were not evaluated.


CONCLUSIONS
Re-treating nonresponders to therapy with peginterferon-alpha2b plus ribavirin for 72 weeks significantly increases SVR rates compared with re-treating them for 48 weeks. The overall SVR rate was low, but patients who are most likely to respond to re-treatment can be identified at week 12.


BACKGROUND
Roche.
Jensen
Donald M
DM
Center for Liver Diseases, University of Chicago Hospitals, Chicago, Illinois 60637, USA. djensen@medicine.bsd.uchicago.edu
Marcellin
Patrick
P
Freilich
Bradley
B
Andreone
Pietro
P
Di Bisceglie
Adrian
A
Brandão-Mello
Carlos E
CE
Reddy
K Rajender
KR
Craxi
Antonio
A
Martin
Antonio Olveira
AO
Teuber
Gerlinde
G
Messinger
Diethelm
D
Thommes
James A
JA
Tietz
Andreas
A
D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; 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 / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D019233:Retreatment; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a