Efficacy of Low-dose Peg-Intron

By Liz Highleyman

The recommended dose of pegylated interferon alfa-2b (Peg-Intron) is 1.5 mcg per kilogram of body weight per week when used in combination with ribavirin, or 1.0 mcg/kg/week when used as monotherapy. Two recent studies looked at the effectiveness of lower doses, which could reduce the cost of therapy and the incidence of side effects.

Study 1 As reported in the June 2006 American Journal of Gastroenterology, the first research team conducted a prospective randomized trial of standard-dose versus low-dose Peg-Intron plus ribavirin. Treatment-naïve patients weighing less than 75 kg received 50 or 100 mcg/week, while those weighing 75 kg or more received 150 mcg/week, all with 1000 mg daily ribavirin. Patients were treated for 24 weeks or 48 weeks, depending on virological response at week 24.

Results

The overall sustained virological response (SVR) rate was 45% for standard-dose Peg-Intron compared with 33% for low-dose therapy (P = 0.02).

For patients with HCV genotypes 2 or 3, the SVR rates were 65% for standard-dose and 56% for low-dose Peg-Intron (P = 0.51).

For patients with genotype 1, the corresponding rates were 38% and 24% (P = 0.03).

For genotype 1 patients whose doses exceeded the so-called "1-2-5" threshold -- that is, at least 1.25 mcg/kg weekly Peg-Intron plus at least 12.5 mg/kg ribavirin daily -- the SVR rate was 51%.

Conclusion

The authors concluded, "The results of this study underscore the importance of adequate dosing of ribavirin as well as pegylated interferons in achieving an SVR when treating genotype 1 chronic hepatitis C patients with combination therapy."

Study 2

The second research team noted that regulatory approval of the 1.5 mcg/kg weekly dose of Peg-Intron in combination with ribavirin was based on a study using Peg-Intron doses of either 0.5 or 1.5 mcg/kg/week, despite previous research showing a flat dose-response curve at doses of 1.0 mcg/kg/week or higher.

As reported in the July 2006 Journal of Viral Hepatitis, they conducted an open-label randomized study of 227 patients with chronic hepatitis C and Metavir fibrosis scores of F2 or lower, comparing 1.0 mcg/kg versus 1.5 mcg/kg weekly Peg-Intron plus 400 mg twice daily ribavirin. Patients were treated for 24 or 48 weeks, depending on genotype.

Results

Sustained virological response rates did not differ significantly between the two doses of Peg-Intron in patients with HCV genotypes 1 or 4.

Among genotype 1 or 4 patients, 38% (22/58) in the 1.0 mcg/kg/wk group achieved SVR, compared with 39% (27/70) in the 1.5 mcg/kg/wk arm (P = ns).

Among patients with genotypes 2 or 3, the corresponding SVR rates were 71% (39/55) vs 81% (29/36) (P = ns).

Adverse events led to temporary or permanent dose reduction in fewer patients in the 1.0 mug/kg/wk dose group (48/113 patients; 42%) compared with the 1.5 mug/kg/wk group (63/106 patients; 59%) (P = 0.015).

89% of patients treated for 24 weeks, but only 58% of those treated for 48 weeks, tolerated therapy without dose reduction or premature termination (P < 0.001).

Conclusion

The authors concluded, "In combination with ribavirin, [Peg-Intron] 1.0 mcg/kg was as effective as 1.5 mcg/kg but was better tolerated in patients with chronic hepatitis C and up to moderate fibrosis."

These two studies are not strictly comparable, since the first team used fixed doses of Peg-Intron for patients above and below the 75 kg threshold (about 165 pounds, a typical weight for a large woman or a small man), and the second study used lower doses of ribavirin, which plays a role in preventing HCV relapse. Further study is needed to clarify optimal Peg-Intron dosing for individual patients.

8/01/06

References

E L Krawitt, S R Gordon, N D Grace, and others. A study of low dose peginterferon alpha-2b with ribavirin for the initial treatment of chronic hepatitis C. American Journal of Gastroenterology. 101(6): 1268-1273. June 2006.

S Meyer-Wyss, P Rich, H Egger, and others. Comparison of two PEG-interferon alpha-2b doses (1.0 or 1.5 mug/kg) combined with ribavirin in interferon-naive patients with chronic hepatitis C and up to moderate fibrosis. Journal of Viral Hepatitis 13(7): 457-465. July 2006.