Retreating chronic hepatitis C with daily interferon alfacon-1/ribavirin after nonresponse to pegylated interferon/ribavirin: DIRECT results

Abstract

Up to 50% of patients with chronic hepatitis C fail to respond to initial therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV). With unsuccessful viral eradication, these patients remain at risk for developing progression of their liver disease. Retreatment with PEG-IFN/RBV yields sustained virologic response (SVR) rates that are under 10%. A wholly synthetic interferon, interferon alfacon-1 or consensus interferon (CIFN) given with RBV, was evaluated in patients who failed initial PEG-IFN/RBV therapy. The intent-to-treat analysis included 487 patients; 245 received CIFN 9 g/day and RBV, and 242 received CIFN 15 g/day and RBV. Within this group of patients, 59.3% had documented advanced fibrosis at baseline liver biopsy (stage F3 or F4). SVR rates were 6.9% (17/245 patients) in the 9 g group and 10.7% (26/242) in the 15 g group. In the intent-to-treat analysis, SVR rates were higher among patients with a >2-log 10 decrease in hepatitis C virus RNA during prior PEG-IFN/RBV therapy: 11% (4/38) in the 9 g group and 23% (7/31) in the 15 g group. Among patients with lower baseline fibrosis scores (F0-F3), SVR rates were 7.8% (15/192) in the 9 g group and 13.1% (23/175) in the 15 g group. In this same group of patients (F0-F3), if a >2-log 10 decrease in hepatitis C virus RNA with previous PEG-IFN/RBV treatment was achieved, SVR rates improved to 10.7% and 31.6% in the 9 g and 15 g groups, respectively. CIFN/RBV combination retreatment was safe and well tolerated. Conclusion: Retreatment of PEG-IFN and RBV nonresponders with CIFN and RBV is safe and efficacious and can be considered a retreatment strategy for patients failing previous therapy with PEG-IFN/RBV, especially in interferon-sensitive patients with lower baseline fibrosis scores.

Efficacy of Treatment With Pegylated Interferon and Ribavirin in Patients With Chronic HCV Infection “Under Real Life“ Conditions

“…Previous treatment was performed with standard interferon alfa 2b and ribavirin mostly (in 2/3 of patients) or with interferon monotherapy and combination of peginterferon plus ri-bavirin in the other third of patients. Low SVR of treatment experienced genotype 1 patients is in accordance with the data of other investigators [50,[57][58][59][60] and are very similar to the findings obtained in observational French study: they found SVR 39 % in ITT population: 43 % in naive and 31 % in treatment-failure patients, but was lower in comparing with the results of others [61]. HCV genotypes are considered as the strongest baseline predictors for response for dual therapy and our data confirmed that: HCV genotype 1 is the major negative predictor of SVR -"difficult to treat genotype" by univariate and multivariate analysis.…”

“…Majority of RCT and community based studies found that high pretreatment viral load and presence of advanced fibrosis or cirrhosis are strong independent negative predictors of SVR in combined antiviral treatment [15,24,25,40,44,[45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62].…”

“…Data regarding those variables are contradictory: some investigators found positive predictivity of ALT activity higher than 3 times UNL and higher HAI scores for SVR [44,59,72,73], the others did not confirm any correlation of ALT and SVR [70].…”

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“…The higher rate of SVR in this study may be attributable to direct transition from PEG to CIFN in cohort A1 to cohort A2. The DIRECT trial had a median washout interval of 506 days between PEG and CIFN initiation, 22 whereas all our patients were transitioned directly. The SVR rate in this study also was greater than a veterans administration trial showing a 6% and 31% SVR rate in nonresponders and relapsers.…”

“…17,20,21 Interferon alfacon-1 or consensus interferon (CIFN) (Infergen, Boehringer Ingelheim, Austria, GmbH) is a synthetic interferon that has been shown to be effective in the retreatment of PEG/RBV nonresponders and partial responders pre-LT to achieve a SVR in 7% to 30% of patients depending on fibrosis stage and prior response to PEG/RBV. 22 There are no published studies of CIFN in the post-LT patient. We sought to evaluate our experience with use of CIFN/RBV for recurrent HCV.…”