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| |  DDW: Pegasys and Ribavirin Effective at 24 weeks in Patients With Hepatitis C and Advanced Fibrosis/Cirrhosis By Larry Schuster SAN FRANCISCO, CA -- May 22, 2002 -- Swiss researchers say 24 weeks of Pegasys (pegylated interferon alfa-2a) and ribavirin cleared Hepatitis C virus RNA in serum in almost 90 percent of patients with advanced HCV-associated fibrosis/cirrhosis. The treatment combination is also acceptably tolerated, reported Dr. Eberhard L. Renner, University Hospital, in Zurich, speaking here Monday at Digestive Disease Week 2002, based on interim results in 88 patients of the investigational drug Pegasys (Roche) and ribavirin at the midpoint of the phase III trial. The treatment phase of the trial continues through to 48 weeks. The researchers compared efficacy and tolerability of PEG-IFN (180ug sc weekly) and RIBA (1000/1200 mg vs. 600/800 mg po QD) in treatment-naive patients with HCV-associated advanced fibrosis/cirrhosis in an open-label, randomized, controlled, trial in 11 Swiss centers. Patients had not previously been treated, included both genders with HCV-associated biopsy-proven advanced fibrosis/cirrhosis (Metavir F3-F4) and less than 8 Child-Pugh points, elevated ALT and positive HCV-RNA in serum (Amplicor® HCV MonitorTM). Randomization (1:1) was stratified according to genotype (2/3 vs. other; Inno-Lipa®) to PEG-IFN (180ug sc once weekly) and either RIBA (75kg or less: 1000mg, >75kg: 1200mg po QD) or (75kg or less: 600mg, >75kg: 800mg po QD) for 48 weeks with 24 weeks of follow-up. So far, 88 patients were enrolled including 40 (45 percent) females; 30 (45 percent) genotype two-three, 40 (45 percent) genotype one. Forty-three patients were randomized to higher, 45 patients to lower RIBA dose. At 24 weeks of treatment, HCV-RNA in serum was negative (<1000 cps/ml) after two, four, eight, 12 and 24 weeks of treatment in 24/71 (34 percent), 36/65 (55 percent), 43/63 (68 percent), 37/53 (70 percent) and 25/28 (89 percent) patients, respectively, with no difference between treatment arms. Treatment prematurely terminated in five (six percent) patients for AEs, of which two were severe (attempted suicide, incidental PEG-IFN over-dose). Dose reduction was necessary in 38 (43 percent) patients with no difference between treatment arms. In which proportion this high initial response rate translates into sustained HCV clearance remains to be seen. Based on previous studies, Renner, head of hepatology at University Hospital, said he expects a sustained clearance in 50 to 60 percent of patients. He said the drug is very similar to Peg Intron A, which is already approved in the United States. Pegasys, which could gain FDA approval by the end of the year, is one amino acid different and is pegylated differently so that the drug is cleared through the liver. In contrast, he said Peg Intron A is cleared through the kidneys, Renner said. Pegasys administration is by ready-to-use syringe. He said he anticipates that Peg Intron A, which now requires the patient to do some preparation of the solution, also will likely adopt a similar system, he said. Investigators targeted patients with advanced fibrosis/cirrhosis because previous studies have tended to exclude this more difficult population, he said. The study was supported by Roche Pharma (Schweiz) AG, Switzerland.
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