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

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Hepatology. 2010 Jun 30. [Epub ahead of print]

Virologic response rates of weight-based taribavirin versus ribavirin in

treatment-naive patients with genotype 1 chronic hepatitis C.

Poordad F, Lawitz E, Shiffman ML, Hassanein T, Muir AJ, Bacon BR, Heise J,

Halliman D, Chun E, Hammond J.

Cedars-Sinai Medical Center, Los Angeles, CA.

Abstract

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. (HEPATOLOGY 2010).

PMID: 20721883

[Guest guest]

Hepatology. 2010 Jun 30. [Epub ahead of print]

Virologic response rates of weight-based taribavirin versus ribavirin in

treatment-naive patients with genotype 1 chronic hepatitis C.

Poordad F, Lawitz E, Shiffman ML, Hassanein T, Muir AJ, Bacon BR, Heise J,

Halliman D, Chun E, Hammond J.

Cedars-Sinai Medical Center, Los Angeles, CA.

Abstract

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. (HEPATOLOGY 2010).

PMID: 20721883