Studies look at effect of lower doses of Peg-Interferon and Ribavirin for people with Genotypes 2 or 3

7th July 2008 By Liz Highleyman hivandhepatitis.com

In an effort to reduce the cost and side effects of treatment for chronic hepatitis C virus (HCV) infection, researchers have explored lower doses of pegylated interferon and/or ribavirin for patients with easier-to-treat HCV genotypes 2 or 3.

As reported in the May 28, 2008 online edition of the Journal of Viral Hepatitis, Swedish researchers assessed whether a lower-than-standard fixed dose of pegylated interferon plus ribavirin for 24 weeks would produce an adequate sustained virological response (SVR) rate for genotype 2 or 3 patients.

As background, they noted that previous research has shown that pegylated interferon monotherapy using a lower-than-standard dose yielded the same SVR rate as standard doses in this population.

In the present study, 100 consecutive chronic hepatitis C patients (59 with genotype 3, 41 with genotype 2) were treated with low-dose 135 mcg/week pegylated interferon alfa-2a (Pegasys) in combination with 11 mg/kg/day ribavirin for 24 weeks; the standard Pegasys dose is 180 mcg/week.

Results

• 70% of genotype 2 patients and 71% with genotype 3 achieved rapid viral response (RVR), or HIV RNA < 15 IU/mL at week 4 of treatment.

• Overall, 85% of genotype 2 patients and 86% with genotype 3 went on to achieve SVR.

• Significantly more genotype 2 patients with RVR achieved SVR (96%) compared with genotype 2 patients who failed to achieve RVR (66%) (P = 0.009).

• For patients with genotype 3, the corresponding SVR rates were 95% with RVR and 65% without RVR (P = 0.002).

"We found that 135 mcg [pegylated interferon] alfa-2a weekly was sufficient for treatment of genotype 2 and 3 chronic hepatitis C when combined with ribavirin dosed daily according to body weight," the investigators concluded. "This combination yielded high SVR rates (85-86%) and may be cost-saving."

In a related analysis, the Australia Hepatitis Study Group assessed the efficacy and tolerability of ribavirin administered at half the standard dose for patients with HCV genotype 2 or 3. Results were reported in the June 2008 issue of Hepatology.

This study included 282 treatment-naive genotype 2 or 3 chronic hepatitis C patients randomly assigned to receive either 400 mg/day or 800 mg/day fixed-dose ribavirin in combination with 180 mcg/week pegylated interferon alfa-2a for 24 weeks.

Results

• Overall, 97 of 141 patients (68.8%) using the standard ribavirin dose achieved SVR, compared with 90 of 141 patients (63.8) using the lower dose.

• Relapse rates in the standard-dose and low-dose groups were similar, at 17% vs 20%, respectively.

• Among genotype 3 patients, the standard-dose and low-dose SVR rates were 67.5% and 63.9%, respectively.

• Among genotype 2 patients, the corresponding SVR rates were more divergent, at 77.8% and 55.6%, respectively.

• The incidence of adverse events, laboratory abnormalities, and dose reductions were similar in the 2 ribavirin dose groups.

Based on these findings, the authors concluded, "The results suggest that when administered for 24 weeks with peginterferon alfa-2a, ribavirin doses of 400 and 800 mg/day produce equivalent outcomes in patients infected with HCV genotype 3."

7/08/08

References

O Weiland, A Hollander, L Mattsson, and others. Lower-than-standard dose peg-IFN alfa-2a for chronic hepatitis C caused by genotype 2 and 3 is sufficient when given in combination with weight-based ribavirin. Journal of Viral Hepatitis. May 27, 2008 [Epub ahead of print].

P Ferenci, H Brunner, H Laferl, and other (for the Australia Hepatitis Study Group). A randomized, prospective trial of ribavirin 400 mg/day versus 800 mg/day in combination with peginterferon alfa-2a in hepatitis C virus genotypes 2 and 3. Hepatology 47(6): 1816-1823. June 2008. Abstract