Hepatitis C Therapy Should Be Individually Tailored; Starting Virus Levels, Genotype Predict Response to Interferon Treatment

PHILADELPHIA, May 8, 2000 /PRNewswire/ — The following was issued today by Patients Network, Inc.:

Viral genotype and baseline virus levels predict response to interferon (IFN) treatment for patients with chronic Hepatitis C virus (HCV) infection. Therapy with interferon alfacon-1 (Infergen, Amgen) should be tailored for each patient’s condition.

Today’s standard treatments do not adjust therapy based on individual patient’s requirements. But patients with genotype 2 or 3 virus generally respond better than those with genotype 1. So do patients with lower baseline virus levels. (About 70% of HCV patients in the U.S. have genotype 1 virus.)

F. Blaine Hollinger, MD, Professor of Medicine, Virology, and Epidemiology at Baylor College of Medicine in Houston, says a clinical trial he did shows that many patients will respond if given enough interferon, “and if you give them daily doses, for example, instead of three times a week or every other day.”

The study he presented at the 1999 meeting of the American Association for the Study of Liver Diseases provides evidence that optimal IFN doses and schedules may differ depending on genotype and baseline virus concentration.

The patients were divided into two groups, according to their baseline levels of virus (HCV RNA levels): low, with less than or equal to 106 copies/ml; and high, with greater than 106 copies/ml.

Researchers compared the effect of five different induction regimens of IFN alfacon-1 on virus elimination in these patients. They received one of five four-week IFN induction regimens: (1) 7.5 mcg twice a day; (2) 15 mcg once daily; (3) 15 mcg three times a week; (4) 9 mcg daily; or (5) 9 mcg three times a week. After the four-week induction period, all subjects received 9 mcg three times a week for an additional 44 weeks.

Patients with low baseline viral concentrations had rapid and consistent decreases in virus levels by week 4 with all induction dosing regimens except 9 mcg three times a week. Within 2 weeks, most patients on the effective regimens had low or undetectable virus levels. Levels continued to decrease or remained low after the 4 week induction period. Patients on the 9 mcg three times a week induction dose required 12 weeks of treatment before their virus levels became undetectable .

Patients with high baseline virus levels did not experience as rapid a decrease as did those with low baseline levels. And for some, levels rebounded after switching to 9 mcg three times a week. The researchers speculate that longer induction periods may be necessary for patients with higher baseline viral loads.

Besides the faster rate of viral decrease in patients with low baseline levels, more of them responded to every induction dosing regimen when measured at 4 and 12 weeks, compared to patients with high levels.

For patients with genotype 1 virus and low baseline virus levels, induction dosing with 15 mcg of IFN daily or 7.5 mcg twice daily produced a more rapid decrease in viral levels than the other induction doses. But genotype 1 patients had rebounds in their virus levels after switching to 9 mcg three times a week. Again, the researchers suggested that longer induction periods may be necessary for these patients.

Based on the rate of viral decrease, the researchers calculated the optimal induction period for genotype 1 patients. A dose of 15 mcg once daily required the shortest induction period, 10.4 weeks, to bring virus down to undetectable levels. The standard dose of 9 mcg three times a week required 13.7 weeks.

The researchers concluded that treatment of chronic HCV patients should be tailored based on their genotype and viral loads. Patients with low baseline viral concentrations or who are not genotype 1 can achieve maximum benefit when treated with 9 mcg of IFN alfacon-1 daily for 4 weeks and then switched to 9 mcg three times a week for 44 weeks. However, patients with high baseline viral levels or who are genotype 1 may do better if treated with 15 mcg of IFN alfacon-1 daily for 10 weeks, followed by 9 mcg three times a week for the duration.

Dr. Hollinger already individualizes therapy based on viral load and genotype, and he goes further by monitoring treatment efficacy along the way. “We often will treat a patient for four weeks with high dose induction therapy, and then look and find out whether they have undetectable virus at that time,” he says. “If they do, then I will switch them to every other day therapy. If they don’t, I’ll continue on for at least 10 weeks of daily therapy and then switch them to every other day after that and continue the therapy for perhaps in that case up to a year instead of six months.”

Besides genotype and viral load, Dr. Hollinger thinks race may be another important parameter to consider. “We haven’t looked yet at the response rates of African Americans versus Caucasians in this study, but I think that’s probably a very important issue as well,” he says. African Americans often have more resistant disease than Caucasians.

A report of Dr. Hollinger’s study and several other highlights from the AASLD meeting are available at the Med On Scene site 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 based on AASLD meeting reports. A service of Patients Network, Inc.

SOURCE Patients Network, Inc.