Virologic response rates of weight-based taribavirin versus ribavirin in treatment-naive patients with genotype 1 chronic hepatitis C.

Abstract

UNLABELLED:

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.

CONCLUSION:

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.

• Authors: Fred Poordad, Eric Lawitz, Mitchell L Shiffman, Tarek Hassanein, Andrew J Muir, Bruce R Bacon, Jamie Heise, Deanine Halliman, Eric Chun, Janet Hammond
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 52 Issue 4 Pg. 1208-15 (Oct 2010) ISSN: 1527-3350 [Electronic] United States
• PMID: 20721883 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Antiviral Agents
• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• peginterferon alfa-2b
• taribavirin

Topics

• Adolescent
• Adult
• Anemia, Hemolytic (chemically induced)
• Antiviral Agents (administration & dosage)
• Body Weight
• Female
• Hepacivirus (genetics)
• Hepatitis C, Chronic (drug therapy)
• Humans
• Interferon alpha-2
• Interferon-alpha (administration & dosage)
• Male
• Middle Aged
• Polyethylene Glycols (administration & dosage)
• Recombinant Proteins
• Ribavirin (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Treatment Outcome
• Viral Load