Hepatitis Central

Five times a week dosing of consensus interferon is twice as effective as the same dose administered three times a week for 48 weeks, according to preliminary results in a study of previously untreated Hepatitis C patients.

For patients in the five times per week group, 69% (9/13) were HCV RNA negative at 12 weeks of treatment. The three times per week group showed a 38% (5/13) HCV RNA negative rate.

A subset of patients has reached the 48 week point in treatment, which is often considered a standard time for evaluating treatment success. For patients who have completed 48 weeks of treatment, 75% of patients (6/8) receiving 15 micrograms of consensus interferon (Infergen) five times a week showed no sign of virus in their blood at 48 weeks, compared to 33% (1/3) who received the same dose of the medication three times a week. All of the patients cited in the end of treatment data had genotype-1 virus.

"The end of treatment data is really exciting," says lead researcher Carl Jones, DO, gastroenterology fellow at Allegheny General Hospital in Pittsburgh, Pennsylvania. "A significant portion of those patients are probably going to have a sustained response." Dr. Jones will soon test four patients who are six months post treatment for sustained viral response. "By the end of June I should have some sustained response data," he says, adding, "But the end of treatment data looks very solid."

Dr. Jones is conducting one of several studies examining the efficacy of induction therapy with consensus interferon - high doses administered more frequently than three times a week. (See Special Report.) The study is tracking 50 previously untreated HCV patients evenly split into two groups, each receiving 15 micrograms consensus interferon for 48 weeks, either three times a week or five times a week. Their HCV RNA levels will be tested six months later to determine sustained response. Genotype-1 patients make up 84% of the subjects. (The total study involves 50 patients. Interim data analyses involve different numbers of patients because patients entered the study at different times and therefore complete treatment "time points" at different times.)

Dr. Jones is encouraged that viral clearance at the end of treatment in his study is significantly higher than has been shown in other studies. He points to the study by Dr. John McHutchison and others that looked at treatment rates with interferon alone and with combination therapy (McHutchison JG et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic Hepatitis C. N Engl J Med. 1998:339:1485-1492). In that study, 29% of patients receiving interferon monotherary and 38% receiving combination therapy had a negative HCV RNA reading at the end of treatment.

"I suspect that a significant portion of [our] patients are going to get a sustained response," says Dr. Jones. "I'm thrilled with the data right now."

Limited side effects

Patients in the five times a week group are tolerating the higher frequency regimen well, Dr. Jones says. Of the total of 50 patients enrolled, only one patient has dropped out of the study, and ten have required dose reductions. Six patients from the five times a week group were reduced to three times a week dosing because of hematologic side effects (thrombocytopenia and neutropenia), and two were reduced because of flu-like symptoms. None of these patients required further dose reductions. Two patients in the three times a week group needed dose reductions for flu-like symptoms.

Dr. Jones notes that patients in the three times a week group experience more flu-like and fatigue symptoms than patients in the five time a week group. "It's an interesting phenomenon," Dr. Jones says. "Fatigue and flu-like symptoms are significantly less in the five time a week arm. What they've been telling me is that when they're off the drug for two days [over the weekend], their worst day is when they go back on Monday. Monday evening they get flu-like symptoms. Tuesday, Wednesday, Thursday, and Friday their symptoms are minimal."

Dr. Jones believes that data from the study will support use of induction therapy for more patients. "I have a couple of patients on seven days a week now that are combination therapy failures, and they are tolerating the 15 micrograms seven times a week," he says. "I think it's a tolerable dose versus higher doses of conventional interferon where you have log[arithmic] increases in the side effects. I'm not seeing that with consensus interferon."

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