Peginterferon alfa-2a (40KD) plus ribavirin in chronic hepatitis C patients who failed previous interferon therapy

Abstract

Background:The management of patients with chronic hepatitis C who have relapsed or failed to respond to interferon based therapies is an important issue facing hepatologists. Aims: We evaluated the efficacy and safety of peginterferon alfa-2a (40KD) plus ribavirin in this population by conducting a multicentre open label study. Patients: Data from adults with detectable serum hepatitis C virus (HCV) RNA who had not responded or had relapsed after previous conventional interferon or conventional interferon/ribavirin combination therapy were analysed. Methods: Patients were retreated with peginterferon alfa-2a (40KD) 180 mg/week plus ribavirin 800 mg/day for 24 or 48 weeks at the investigators' discretion. The study was conceived before the optimal dose of ribavirin (1000/1200 mg/day) for patients with genotype 1 was known. The primary endpoint was sustained virological response (SVR), defined as undetectable HCV RNA (,50 IU/ml) after 24 weeks of follow up. The analysis was conducted by intention to treat. Results: A total of 312 patients (212 non-responders, 100 relapsers) were included. Of these, 28 patients were treated for 24 weeks and 284 for 48 weeks. Baseline characteristics between non-responders and relapsers were similar although more non-responders had genotype 1 infection (87% v 69%). Overall SVR rates were 23% (48/212) for non-responders and 41% (41/100) for relapsers. When data were analysed by genotype, SVR rates were 24% (61/253) in genotype 1 and 47% (28/59) in genotype 2/3. Conclusions: These results in a large patient cohort demonstrate that it is possible to cure a proportion of previous non-responders and relapsers by retreating with peginterferon alfa-2a (40KD) plus ribavirin.

Retreatment of hepatitis C patients who previously experienced treatment failure

“…Some authors showed that, after previous treatment with conventional IFN, with or without RBV, relapsers have significantly higher SVR when retreated with PEG-IFN alpha-2b and RBV than do nonresponders to previous treatment (55% vs. 20%; p<0.001) [9]. The same was observed by Sherman et al, who found that, after retreatment with PEG-IFN alpha-2a and RBV, the SVR rate was 23% in nonresponders and 41% in relapsers [12]. The results of the retreatment of true nonresponders to PEG-IFN and RBV obtained by the Brazilian researchers are better than those reported in international studies [10,11].…”

“…Of the relapsers treated, 57% [10] and 62% [11] achieved an SVR. These SVR rates in relapsers are higher than, for example, the rates of 41% and 59% obtained, respectively, in Canada (by Sherman et al) and in France (by Moucari et al) [12,13]. In analyzing the response in relapsers by genotype, the Brazilian researchers found that an SVR was achieved in 69-70% of those infected with genotype 3, compared with 43-44% of those infected with genotype 1 [10,11].…”

Retreatment with pegylated interferon plus ribavirin of chronic hepatitis C non-responders to interferon plus ribavirin: A meta-analysis

“…Of the remaining 42 full-text articles, 30 were excluded because they did not meet inclusion criteria, leaving 14 fulllength papers [3][4][5][6][7][8][9][10][11][12][13][14][15][16] meeting criteria for inclusion in the meta-analysis. Finally, 6 abstracts identified by manual search [17][18][19][20][21][22], were also included, only for the evaluation of the publication bias.…”

“…Several studies of retreatment with pegylated IFN (PEG-IFN) plus ribavirin in patients who failed to respond to the combination of pegylated and non-pegylated IFN plus ribavirin have been published [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. The results of these studies are inconclusive or conflicting because of the relatively small samples and the differences in patient characteristics, study design combining relapsers and nonresponders, doses of IFN and ribavirin administered in the first course, and retreatment regimens.…”

Efficacy and safety of simeprevir in combination with peginterferon and ribavirin for patients with hepatitis C genotype 1 infection: A meta-analysis of randomized trials

“…Therefore, we believe that the addition of SMV to PegIFN/RBV may significantly improve the SVR. AEs in these included RCTs were clinically manageable and the most common AEs caused by the triple regimen were headache, fatigue, and influenza-like illness; all of which were well-known AEs associated with the dual regimen (28)(29)(30)(31)(32)(33)(34)35). Our meta-analysis showed that the pooled incidence of AEs with triple therapy was similar to that with the dual regimen, suggesting that addition of SMV to PegIFN/RBV at least did not exacerbate the AEs of the dual regimen.…”