Weight-Based Ribavirin with Peginterferon Boosts Virologic Response in HCV

From Digestive Disease Week 2006

Ira M. Jacobson, MD

LOS ANGELES?Patients with chronic hepatitis C virus (HCV) infection have significantly better outcomes when weight-based (rather than fixed) dosing of ribavirin (eg, Copegus, Rebetol) is combined with peginterferon alfa-2b (Peg-Intron) therapy, reported investigators at Digestive Disease Week.

The new data from the Weight-Based Dosing of PEG-Intron and Rebetol (WIN-R) trial also showed that the combination resulted in higher rates of sustained virologic response in patients with HCV genotype 1 (HCV-1), which is more difficult to treat than HCV-2 or HCV-3, and that 24 weeks of weight-based therapy for patients with HCV-2 or HCV-3 is as effective as 48 weeks of treatment for achieving sustained virologic response.

"These WIN-R findings help us better understand how to optimize hepatitis C treatment for our patients and how certain patient characteristics affect response to therapy in real-world community settings," said Ira M. Jacobson, MD, chief of the division of gastroenterology and hepatology at New York-Presbyterian Hospital/Weill Cornell Medical Center, New York City.

WIN-R included 4913 patients with HCV infection who were randomized to receive 1.5 ?g/kg peginterferon alfa-2b weekly, combined with ribavirin as a fixed 800-mg daily dose or a weight-based daily dose of 800 mg for patients weighing <65 kg; 1000 mg for those weighing 65 to 85 kg; 1200 mg for 86 to 105 kg; and 1400 mg for 106 to 125 kg.

Patients with HCV-1 were treated for 48 weeks; those with HCV-2 or HCV-3 were randomized to treatment for either 24 or 48 weeks.

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Among all patients, sustained virologic response was achieved by 44% of those receiving weight-based dosing of ribavirin compared with 41% with the fixed dose ( = .01). In those with HCV-1 infection, sustained response was achieved by 34% of those receiving weight-based dosing compared with 29% in the fixed-dose groups ( = .004).

WIN-R included a total of 1829 patients with HCV-2 or HCV-3 infection. In these patients, 24 weeks of combination therapy was as effective, and better tolerated, than 48 weeks of treatment. Overall, in the weight-based dosing arms, the sustained virologic response rate was 68% in the 24-week group and 60% in the 48-week treatment group.

Patients in the 24-week treatment arm with genotype 2 had a sustained response of 71% compared with 60% for those with HCV-3; relapse rates were 6% for those with HCV-2 and 10% for those with HCV-3.

Investigators concluded that a 24-week combination treatment course with a fixed dose of ribavirin is sufficient for patients with HCV-2 but weight-based doses of ribavirin may benefit those with HCV-3 who have a high viral load.

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For patients with stage 0 to 2 fibrosis, no difference was seen in virologic response between the weight-based and the fixed-dosed ribavirin dosing. However, in patients with stage 3 to 4 fibrosis, sustained response was 43% in the weight-based dose group compared with 37% in the fixed-dose group ( = .02).

The investigators therefore recommend weight-based ribavirin dosing to increase virologic response in patients with advanced fibrosis or cirrhosis.

In other HCV research, treatment with an investigational oral protease inhibitor, VX-950 (Vertex Pharmaceuticals), 750 mg 3 times daily, combined with standard doses of pegylated interferon alfa-2a (Pegasys) and ribavirin for 28 days reduced viral load to undetectable levels in all 12 HCV-1 patients. After 12 weeks of follow-up treatment with pegylated interferon and ribavirin alone, 11 patients maintained undetectable viral loads.

"These results are highly encouraging for the initiation of future VX-950 studies that seek to evaluate the potential for viral eradication with short- duration therapy," said lead investigator Eric Lawitz, MD, Alamo Medical Research, San Antonio, Tex.