Daily High-Dose Infergen Treatment Clears Hepatitis C Virus Better than Standard Dosing

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An intensive initial course of interferon therapy provides the best clearance of hepatitis C virus from the blood in patients with chronic infection. In a study of different doses and schedules of administration of interferon alfacon-1 (Infergen, Amgen), "induction therapy" with 15 mcg daily provided the greatest reduction in virus at week 4. Patients with either high or low baseline viral titers benefited.

No ideal treatment yet exists for chronic HCV infection, and treatment failure is a common outcome. While longer duration and combination therapy including ribavirin have helped to some degree, better treatment options are needed, especially to improve the initial response rates.

At the November meeting of the American Association for the Study of Liver Diseases, Paul Pockros, M.D., head of the Gastroenterology Division at Scripps Clinic in La Jolla, California presented early results on 169 patients in his ongoing multi-center trial to see if induction therapy could improve the early virologic response without causing substantial side effects.

These treatment-naïve patients were stratified into two groups according to baseline HCV RNA levels: less than or equal to 106 copies/ml, and greater than 106 copies/ml. They received one of five, 4-week interferon alfacon-1 dosing regimens: 7.5 mcg twice a day; 15 mcg once daily; 15 mcg three times a week; 9 mcg once daily; and 9 mcg three times a week. After the 4-week induction period at one of these doses, all patients received 44 weeks of 9 mcg interferon alfacon-1 three times a week, followed by 24 weeks of observation.

The greatest reduction in HCV RNA levels at the end of the four-week induction period occurred in the patients who received 15 mcg daily, for patients with high or low baseline viral levels.

At week 4, once or twice daily induction therapy, as well as 15 mcg TIW, resulted in undetectable HCV RNA in 25-29% of patients who started out with high baseline viral titers. For patients with low baseline titers, once or twice daily induction therapy produced undetectable virus in 64-78% of the patients in the groups at week 4.

A twice daily dose of 7.5 mcg appeared to produce less viral suppression than did 15 mcg once a day when measured at the end of the induction period for the high viral baseline patients. However, this difference was not statistically significant.

Patients tolerated induction with 15 mcg once a day well. But 7.5 mcg twice daily caused almost three times the need for dose reductions and twice the number of drug discontinuations during the induction period compared to 15 mcg once a day. The reason for this finding was not apparent, considering the total daily dose is the same.

Induction dosing with 15 mcg of interferon alfacon-1 once a day appeared to be best at reducing viral levels, according to the interim results of this study. "I think this was a well tolerated regimen," Dr. Pockros said. "I think the key take home lesson here is that patients can handle the daily dosing. It's a reasonable approach to treatment."

Looking ahead, the study suggests that combining strategies to treat HCV infection may prove useful. "I think the real clinical implication will be that induction dosing may be the correct strategy when you combine this drug with ribavirin," Dr. Pockros suggested. "And that trial is being initiated right now, where we're using induction dosing at 9 mcg daily plus ribavirin." His thought is that ribavirin may help reduce the rate of relapse when added to an induction regimen using interferon alfacon-1.

Reports of Dr. Pockros' study and several others from the AASLD meeting are available at Med Onscene at http://www.medonscene.com. The site offers health professionals the opportunity to earn continuing medical, nursing, or pharmacy education credits by completing the educational activity in liver disease.
Distributed by: Patients Network; A service of Patients Network, Inc.


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