By Liz Highleyman

Given the suboptimal response to interferon-based therapy for chronic hepatitis C virus (HCV) infection -- especially for patients with hard-to-treat HCV genotype 1 -- researchers have explored alternative treatment strategies including variable durations based on early response.

At the recent 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008) in San Francisco, Peter Ferenci and colleagues from Austria reported results from a study of response-guided therapy based on HCV viral load levels at weeks 4 and 12 of therapy.

This prospective study included 551 chronic hepatitis C patients with HCV genotypes 1 or 4. Most (about 65%) were men and the mean age ranged from 41 to 47 years.

All participants started treatment with 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000-1200 mg/day weight-adjusted ribavirin. Those who did not achieve rapid virological response (RVR), defined as HCV RNA < 50 IU/mL at week 4, were randomly assigned to complete a total of 48 or 72 weeks of treatment. In the latter group, the pegylated interferon dose was reduced to 136 mcg/week starting at week 49.

Complete early virological response (EVR) was defined as HCV RNA > 50 IU/mL at week 4 but < 50 IU/mL at week 12. Partial EVR was defined as HCV RNA > 50 IU/mL at week 4 and > 50 IU/mL at week 12, but with > 2 log drop. Participants who did not achieve EVR were offered the opportunity to continue treatment until week 24. If HCV RNA had become undetectable at that point, they were assigned to 72 week treatment. All patients stopped therapy if HCV RNA remained detectable at week 24.

Sustained virological response (SVR) was defined as undetectable HCV RNA (< 50 IU/mL) after 24 weeks of post-treatment follow-up.

Results

• 517 patients completed 4 weeks of therapy.

• Within this group, 289 patients had detectable HCV RNA at week 4 but ? 2 log drop by week 12, and therefore were randomized to 48 or 72 week treatment.

• Similar proportions of patients achieved an end-of-treatment (EOT) response in the 72 week and 48 week groups (73% vs 77%, respectively).

• However, the relapse rate was significantly lower in patients treated for 72 weeks rather than weeks (19% vs 34%, respectively).

• Thus, in an intent-to-treat analysis, the SVR rate was higher in the 72 week group compared with the 48 week group (59% vs 51%, respectively).

• Among patients with complete EVR at week 12, SVR rates were 72% in the 48 week group and 83% in the 72 week group.

• Among those with partial EVR at week 12, the corresponding SVR rates were 31% and 37%, respectively.

• The relapse rate was higher for genotype 4 patients.

• Low baseline HCV RNA (< 400,000 IU/mL) and less extensive fibrosis were predictors of sustained response.

Based on these findings, the investigators concluded, "Response-guided therapy is an effective strategy for optimizing treatment of patients infected with HCV genotype 1 [or] 4."

"The drop-out rate is higher in patients assigned to a 72-week regimen," they continued, "thus additional support is needed for those undergoing extended treatment to minimize drop-out and maximize SVR."

However, they stated, "The additional safety burden of a 72-week treatment was acceptable in light of the reduction in the rate of relapse."

Internal Medicine 3, Medical University of Vienna, Wien, Austria; Department of Internal Medicine, Kaiser-Franz-Josef-Spital, Wien, Austria; Department of Internal Medicine IV, Wilhelminenspital, Wien, Austria; Department of Internal Medicine, Elisabethinen Hospital, Linz, Austria; Department of Internal Medicine I, Hospital Hietzing, Wien, Austria; Department of Internal Medicine, Medical University, Graz, Austria; Department of Internal Medicine IV, Rudolfshospital, Wien, Austria; LKH Hörgas-Enzenbach, Gratwein, Austria; Krankenhaus, Oberndorf, Austria; Roche Austria, Wien, Austria.

11/18/08

Reference
P Ferenci, H Laferl, T Scherzer, and others. Response-guided therapy with peginterferon alfa-2a (40KD) plus ribavirin in patients with chronic hepatitis C genotype 1 or 4: Prospective randomized study of extended therapy in patients without a rapid virological response. 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008). San Francisco. October 31-November 4, 2008. Abstract 116.