| Head-to-Head Study Compares Early Impact of Peginterferon Alfa-2a and Peginterferon Alfa-2b in Treatment-na飗e Patients with HCV Genotype 1
Two pegylated interferons are currently available for the treatment of chronic hepatitis C (CHC), peginterferon alfa-2a (40KD) (Pegasys) and peginterferon alfa-2b (12 KD) (Peg-Intron). These formulations have different pharmacokinetic (PK) profiles which may result in differential viral clearance.
In this report, researchers present interim results of PK and changes in HCV-RNA levels during the first 8 weeks of treatment with both pegylated interferons in combination with equal dose of ribavirin (RBV; Copegus or Rebetol in CHC patients.
A total of 344 genotype 1, interferon na飗e, high viral load (> 800,000 IU/mL) HCV patients will be randomized to weekly treatment with either Pegasys 180 μg or PEG-Intron 1.5 μg/kg, plus RBV 1000-1200 mg daily, for a total of 12 weeks.
Patients will return weekly for their pegylated interferon injection, safety assessments, serum HCV-RNA measurements and serum trough interferon levels by RIA.
Results
At this time, 107 patients have completed ≥4 weeks and 83 patients have completed ≥8 weeks of therapy.
Baseline characteristics, including body weight, were similar between patient groups. PK parameters for weeks 1-4 have been assayed in 28 patients.
Week 4 trough serum concentrations (Mean ?SEM) of the protein moieties of Pegasys and Peg-Intron were 9670 ?449 pg/mL and 256 ?140 pg/mL, respectively. Mean HCV-RNA changes from baseline (log10) at week 8 in the PEGASYS/RBV arm was 3.22 ?0.236 and 2.65 ?0.279 in the PEG-Intron/RBV arm (Figure).
Total HCV clearance over 8 weeks as measured by area under the virus-load time curve (HCV-AUC) minus baseline (mean AUCMB ?SEM) were 15.8 ?1.47 and 14.3 ?1.65 for each combination, respectively.
At week 4, 22/53 patients in each group had ≥2 log10 drop or negative HCV-RNA (responders); at week 8, the numbers of responders were 29/44 on Pegasys and 22/44 on Peg-Intron, respectively.
No patients have discontinued from the Pegasys/RBV arm due to adverse events; 1 patient (2%) has discontinued from the Peg-Intron/RBV arm due to adverse events.
No unexpected adverse events related to either study medication have been noted.
Conclusion
In conclusion, the authors write, 揑nterim results suggest a difference between the forms of pegylated interferon for PK and viral clearance in patients with chronic HCV genotype 1.?/span>
揟he data collected thus far indicate (1) Pegasys achieves high and persistent interferon trough serum levels for the first 4 weeks of treatment; (2) at week 8, mean log10 HCV-RNA decreases were 3.22 ?0.236 in patients treated with Pegasys versus 2.65 ?0.279 in those treated with Peg-Intron.?
Commentary
Called PEAK (Pegasys Early virologic response And Kinetics), the present study compares early viral load reductions with Pegasys and Peg-Intron and uses equal doses of ribavirin and the same ribavirin dose reduction schedules for managing side effects.?This allows for a balanced comparison of early viral load reductions with Pegasys and Peg-Intron in this trial.?
揟he goal of hepatitis C therapy is to push levels of the virus down to an undetectable level and keep them there.?These interim results show that in patients who completed eight weeks of therapy average levels of the virus were lower in patients treated with Pegasys compared to patients treated with Peg-Intron,?said Adrian M. Di Bisceglie, MD, Chief of Hepatology, Saint Louis University School of Medicine, and the study抯 lead investigator.?揟his study will end at week 12, the point at which early virologic response is determined.?Research has shown that patients who do not respond by week 12 are unlikely to respond to a full course of treatment. ?/font>
揑t is very important to note that PEAK will enable physicians to make an unbiased head-to-head comparison of the early viral kinetics effects of Pegasys and Peg-Intron on viral load because the medications will be administered with the same ribavirin dosing regimen,?said Juan Carlos Lopez-Talavera, M.D., Ph.D., Senior Medical Director, Roche.牋 揥e are very excited by the preliminary findings from PEAK and expect to see final results by the end of 2005.?/font>
Author Disclosure Block: A.M. Di Bisceglie, Roche Laboratories, Inc. C, I; Schering Plough C; V.K. Rustgi, Roche Laboratories, Inc. C, I; Schering Plough O; P. Thuluvath, Roche Laboratories, Inc. I; M. Davis, Roche Laboratories, Inc. I; R. Ghalib, Roche Laboratories, Inc. I; M.F. Lyons, Roche Laboratories, Inc. I; M.S. Ondovik, Roche Laboratories, Inc. E; J. Lopez-Talavera, Roche Laboratories, Inc. E; F. Hamzeh, Roche Laboratories, Inc. E.
11/01/04 Reference
A M Di Bisceglie and others. Pharmacokinetics and Pharmacodynamics of Pegylated Interferon Alfa-2a or Alfa-2b with Ribavirin in Treatment Naive Patients with Genotype 1 Chronic Hepatitis C.?Abstract LB-18 (oral). 55th AASLD. October 29-November 2, 2004. Boston, MA. | 
发表于 2004-11-3 00:34
