Tolerability And Early Efficacy Of Pegylated Consensus Interferon-α (PEG-CIFN) In The Treatment Of Chronic Hepatitis C

Background:Hepatitis C is a challenge worldwide, approvedanti-HCV medications hasn’t been shown to be efficacious to allpatients.Some where are difficult to treat could benefit from Consensusinterferon (CIFN), pegylated CIFN were expected to be more effectiveand safer.Objective:To explore and evaluate the tolerance and antiviralactivity of pegylated recombinant human consensus interferon-α variant（PEG-CIFN）in adults with HCV infection and develop a new safer andmore effective peginterferon.Methods:48adult subjects chronically infected with HCV weretreated by a new peg-interferon(The recombinant human consensusinterferon-α variant (PEG-CIFN)）in a phase one clinical trial. They weredivided into5groups：PEG-CIFN1.0μg/kg (10people), PEG-CIFN1.5μg/kg(10people), PEG-CIFN2.0μg/kg (9people), PEG-CIFN3.0μg/kg (10people) for dose escalation, Pegasys180μg (9people) is positivecontrol.The subjects were treated for4weeks in PEG-CIFN3.0μg/kggroup to evaluate tolerance. The other subjects were treated for14weekswith subcutaneously once a week and were not given drug at the secondand14thweek due to pharmacokenatic blood collection. Symptoms wereobserved and laboratory tests, collected to monitor adverse reactions andadjusting drug dosage, and to evaluate safety and tolerance. HCV RNA level were tested by COBAS Taqman HCV Test system of Roche at the0thweek,4thweek,8thweek and14thweek.Results:Adverse events were well tolerated and none led todiscontinuation of treatment in all dose groups in study period. Theeffects of all PEG-CIFN groups on Platelet drop is weaker than that of Pegasys.The Rapid virologic response (RVR) of PEG-CIFN1.5μg/kg group,PEG-CIFN2.0μg/kg group,PEG-CIFN3.0μg/kg and Pegasys180μg groupwere70%(7/10),77.8%(7/9),(60%,6/10),77.8%(7/9) respectively. They weresignificantly higher than that in PEG-CIFN1.0μg/kg group (10%,1/10)(p<0.05).The Extended rapid virologic response (eRVR) of PEG-CIFN1.0μg/kg group, PEG-CIFN1.5μg/kg group, PEG-CIFN2.0μg/kg groupand Pegasys180μg group were10%(1/10),70%(7/10),77.8%(7/9),66.7%(6/9)respectively.The Early virologic response (EVR) of PEG-CIFN1.0μg/kggroup, PEG-CIFN1.5μg/kg group, PEG-CIFN2.0μg/kg group and Pegasys180μg group were30%(3/10),90%(9/10),88.8%(8/9),88.8%(8/9) respectively.Conclusions:PEG-CIFN (1.0,1.5,2.0,3.0μg/kg)was well toleratedand was found to have dose-dependent effectiveness in chronic hepatitisC subjects.The virological response rates between PEG-CIFN1.5,2.0μg/kg and pegylated IFNα-2a are close, there were no statisticaldifference. The patients who infected1b HCV may have good curativeeffect. Comprehensive consideration, PEG-CIFN1.5μg/kg can be usedas clinical recommended dose. In the treatment of4weeks,8weeks,14weeks, PEG-CIFN is superior to pegylated IFNα-2a in maintainingplatelet levels.