May 22, 2001 (Atlanta) -- Cure is not a word used lightly by doctors, researchers, or patients. But here at the Digestive Disease Week conference, the word is being used in connection with two combination therapies for hepatitis C.
Last fall, there was a report that a more active, once-weekly form of a drug called interferon -- when combined with the antiviral drug ribavirin -- appears to cure more than half of the people with hepatitis C virus who participated in the study. Now, new findings presented at the conference show that a second version of this interferon, combined with ribavirin, also works well to treat hepatitis C.
The new interferons are called "pegylated" versions, because they are linked to a chemical called polyethylene glycol, or PEG. This makes the drugs stay in the body much longer. Instead of the frequent injections needed for standard interferon, a patient needs only one shot per week of the new PEG-interferons. But that's not the only difference -- the PEG-interferons work much better than standard interferon both alone and in the current state-of-the-art combination with ribavirin.
The FDA already has approved PEG-Intron, made by Schering. The new findings reported here show that Pegasys, made by Roche, works about as well as PEG-Intron in combination with ribavirin. Overall, 56% of patients who got the new Pegasys/ribavirin combination were still hepatitis C negative 24 weeks after taking the drugs for 48 weeks. This is close to the 61% of patients who had a sustained response to Schering's PEG-Intron/ribavirin combination in an earlier study, in which dosages of the PEG-interferon were adjusted for patients' body weight.
"And sustained response means clearance of the virus with [the body's own] normal liver enzymes six months after the end of treatment, which at that point implies a cure," says Michael W. Fried, MD, who reported the new Pegasys/ribavirin findings. Fried is director of clinical hepatology at the University of North Carolina, Chapel Hill.
"When I started therapy I felt really, really tired --- I just wanted to sleep all the time," Marichal tells WebMD. "It was hard to do simple things like taking groceries from the car without having to lie down for an hour. And it got progressively worse, although after about six months I got used to it. Also I started getting hives, and that was really bad. I had to take Benadryl, and that made me even sleepier. I also got really depressed. I felt like crying all the time, and I couldn't understand what was happening to me. So they put me on Paxil for that, but that had side effects, too."
Depression, fatigue, and flulike symptoms are common among people who take interferon therapy. And ribavirin causes birth defects, so both women and men must avoid conceiving a child while taking the drug. But even though she suffered from the treatment, Marichal is very happy.
"I would do it again -- being cured is the end result," she says.
Most hepatitis C patients in the U.S. are infected with a strain of hepatitis C called genotype 1 -- the hardest of all hepatitis C strains to cure. In the new Pegasys/ribavirin study, 46% of people infected with genotype 1 became hepatitis C negative and stayed that way. In the earlier PEG-Intron/ribavirin study, this occurred in 48% of genotype 1 patients.
The new study compared 453 patients taking Pegasys/ribavirin with 224 patients taking Pegasys alone (plus a fake injection to simulate combination therapy), and with 444 patients getting standard interferon/ribavirin treatment. Any patient not responding within 12 weeks was offered the chance to switch treatment. Among standard-treatment patients, 45% had a sustained response, while only 30% had sustained responses to Pegasys alone. The response, though, was 56% among patients on the new combination therapy.
One important study finding was that a majority of the patients who became hepatitis C negative did so early in the treatment. This gives doctors an early chance to see whether the drug combination is working -- and to switch treatments if it is not.
All of the patients in this and previous large-scale trials of PEG-interferon had never taken interferon before. But another important study reported here shows that the new drugs can work even in patients for whom standard daily-dose interferon/ribavirin therapy didn't work.
Ira M. Jacobson, MD, chief of the division of gastroenterology and hepatology at Weill Medical College of Cornell University in New York, reported combined results for patients who had failed standard interferon/ribavirin treatment and were taking one of two different doses of PEG-Intron/ribavirin.
Halfway through their 48 weeks of treatment, 35% of these difficult-to-treat patients were hepatitis C negative.
"These studies are important because they investigate possible new treatment options for patients with disease [that is resistant to treatment], in whom it is difficult to achieve a sustained response," Jacobson says.