Virologic response rates of weight-based taribavirin versus ribavirin in treatment-naive patients with genotype 1 chronic hepatitis C.
Ribavirin-induced hemolytic anemia can prompt dose reductions and lower sustained virologic response (SVR) rates in the treatment of patients with chronic hepatitis C. The study aimed to determine if weight-based dosing of taribavirin (TBV), an oral prodrug of ribavirin (RBV), demonstrated efficacy comparable to RBV while maintaining its previously demonstrated anemia advantage with fixed dose administration. A U.S. phase 2b randomized, open-label, active-controlled, parallel-group study was conducted in 278 treatment-naive patients infected with genotype 1 who were stratified by body weight and baseline viral load. Patients were randomized 1:1:1:1 to receive TBV (20, 25, or 30 mg/kg/day) or RBV (800-1400 mg/day) with pegylated interferon alfa-2b for 48 weeks. The SVR rates in this difficult-to-cure patient demographics (mean age, 49 years; 61% male; 30% African American or Latino; high viral load; advanced fibrosis; and mean weight, 82 kg) were 28.4%, 24.3%, 20.6%, and 21.4% in the 20, 25, and 30 mg/kg TBV groups and the RBV group, respectively. There were no statistical differences in the efficacy analyses. Anemia rates were significantly lower (P < 0.05) in the 20 and 25 mg/kg/day TBV treatment groups (13.4% and 15.7%, respectively) compared to RBV (32.9%). The most common adverse events in all groups were fatigue, diarrhea, and insomnia. Diarrhea, reported in 38% of TBV patients versus 21% of RBV patients, was generally mild and not dose-limiting.


CONCLUSIONS
All TBV doses demonstrated efficacy and tolerability comparable to that of RBV; however, the 25 mg/kg dose demonstrated the optimal balance of safety and efficacy. Anemia rates were significantly lower for TBV given at 20-25 mg/kg than RBV. These data suggest weight-based dosing with TBV provides a safe and effective treatment alternative to RBV for chronic hepatitis C. American Association for the Study of Liver Diseases.
Poordad
Fred
F
Hepatology and Liver Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. fred.poordad@cshs.org
Lawitz
Eric
E
Shiffman
Mitchell L
ML
Hassanein
Tarek
T
Muir
Andrew J
AJ
Bacon
Bruce R
BR
Heise
Jamie
J
Halliman
Deanine
D
Chun
Eric
E
Hammond
Janet
J
D000293:Adolescent; D000328:Adult; D000743:Anemia, Hemolytic / Q000139:chemically induced; D000998:Antiviral Agents / Q000008:administration & dosage; D001835:Body Weight; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C026956:taribavirin