Pegylated interferon alfa-2b plus ribavirin in the retreatment of interferon-ribavirin nonresponder patients.
OBJECTIVE
Inadequate data are available about retreatment of nonresponders to interferon (IFN) and ribavirin. Thus, this study evaluated the efficacy and tolerability of a 48-week therapy with pegylated IFN-alpha-2b plus high-dose ribavirin in patients who have failed to respond to the combination. Treatment up to 48 weeks also in patients who have failed to clear hepatitis C virus (HCV) RNA by week 24 was also evaluated.


METHODS
One hundred forty-one patients who previously did not respond to IFN and ribavirin, 86% with genotype 1 or 4 infection, 52% with high viral load (>800.000 IU/mL), 22% with cirrhosis, were retreated with pegylated IFN-alpha-2b 1.5 microg/kg per week and ribavirin 1000-1200 mg/day for 48 weeks and followed up for 24 weeks.


RESULTS
By intent-to-treat analysis, 20% of patients achieved a sustained virologic response (SVR). SVR of genotype 1 patients was 19%. Independent predictors of SVR were low gamma-glutamyltransferase levels (OR, 22.9; 95% CI: 6.6-79.6) and low viral load (OR, 3.8; 95% CI: 1.1-12.6). Twelve (23%) out of 51 patients who were HCV RNA positive after 24 weeks of therapy achieved a late virologic response (after week 24) and 5 (10%) of them, all with genotype 1, achieved an SVR. Genotype was not associated with response (P = .2) or with early response (P = .3).


CONCLUSIONS
Retreatment with pegylated IFN-alpha-2b and ribavirin of multi-experienced and "difficult to treat" nonresponder patients produced a very promising SVR. Accurate selection of patients, such as those with low viral load and low gamma-glutamyltransferase levels, and prolongation of therapy beyond 24 weeks also in HCV RNA-positive patients may further increase the rate of SVR.
Taliani
Gloria
G
Department of Infectious and Tropical Diseases, La Sapienza University, Rome, Italy. gloria.taliani@uniroma1.it
Gemignani
Giulia
G
Ferrari
Carlo
C
Aceti
Antonio
A
Bartolozzi
Dario
D
Blanc
Pier Luigi
PL
Capanni
Marco
M
Esperti
Francesco
F
Forte
Paolo
P
Guadagnino
Vincenzo
V
Mari
Terenzio
T
Marino
Nicoletta
N
Milani
Stefano
S
Pasquazzi
Caterina
C
Rosina
Floriano
F
Tacconi
Danilo
D
Toti
Mario
M
Zignego
Anna Linda
AL
Messerini
Luca
L
Stroffolini
Tommaso
T
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D007372:Interferons / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D019233:Retreatment; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load; D005723:gamma-Glutamyltransferase / Q000097:blood
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D007372:Interferons; D005723:gamma-Glutamyltransferase; C417083:peginterferon alfa-2b