Neil Canavan

December 06, 2011

December 6, 2011 (San Francisco, California) — Adding the recently approved protease inhibitor telaprevir to pegylated interferon (peginterferon) plus ribavirin therapy achieved a 47% sustained viral response (SVR) in hard-to-treat patients with hepatitis C virus (HCV) infection and cirrhosis who had previously failed the standard 2-drug regimen. This finding comes from a subset analysis of the phase 3 REALIZE trial, presented here at The Liver Meeting 2011: American Association for the Study of Liver Diseases 62nd Annual Meeting.

The REALIZE investigators originally looked at telaprevir in combination with peginterferon plus ribavirin in patients with HCV genotype 1 who had had a previous null or partial response, or who had relapsed after treatment with the 2-drug regimen. REALIZE had 3 treatment groups — 2 with different schedules of triple therapy and a third with placebo plus the 2-drug regimen.

Stanislas Pol, MD, PhD, from the Université Paris Descartes, Institut National de la Santé et de la Recherche Médicale, and Assistance Publique-Hôpitaux de Paris, Cochin Hospital, France, and colleagues performed the subanalysis of the REALIZE trial to gauge the effect of triple therapy on a subset of patients with Child class A cirrhosis who had responded poorly to the 2-drug regimen. "For this analysis, we pooled the 2 telaprevir arms since there was no difference in safety and efficacy" between the 2, he explained.

The REALIZE study population consisted of 169 patients with cirrhosis (stage F4) and 493 patients without cirrhosis (stages F0 to F3). For the entire cohort, median age was 52 years, 93% was white, 88% had an HCV RNA level of at least 800,000 IU/mL, and median body mass index was 28 kg/m². Just more than half of the patients were infected with HCV genotype 1a.

There were more null responders in the group with cirrhosis (36% vs 25%), but fewer relapsers (43% vs 57%).

Results showed that in patients with no, minimal, or portal fibrosis (F0 to F2), SVR was achieved in 75% of patients receiving telaprevir and in 22% of those receiving placebo.

"If we consider SVR according to fibrosis stage and prior response, we see no clear impact of fibrosis stage on the overall SVR rate of around 85%. For prior partial responders, there was a significant impact by fibrosis stage, with a decrease in SVR rate from 77% to 56% in patients with mild fibrosis, declining to 34% in those patients with cirrhosis," Dr. Pol told Medscape Medical News.

In previous null responders, the SVR rate after triple therapy was 41% in the patients without cirrhosis, 42% in those with mild fibrosis, and 14% in those with cirrhosis.

More than half (53%) of these previously treated patients with cirrhosis did not achieve an SVR with the addition of telaprevir, compared with 27% of patients without cirrhosis.

Regarding safety, the prevalence of rash was higher in patients with than without cirrhosis (67% vs 53%), but other rates for common adverse events were similar. For hematologic events, anemia was more frequent in patients with cirrhosis (42% vs 34%). In addition, neutropenia was higher (25% vs 17%) and, "as might be expected, platelet counts were lower in the cirrhotic subset," Dr. Pol noted.

Can Early Responders Stop Treatment?

The relatively high response rate in patients with cirrhosis and HCV who had failed previous treatment with peginterferon and ribavirin raises the question of whether treatment can be stopped early with triple therapy.

Michael Bernstein, MD, director of the hepatitis clinic at the Coney Island Hospital, Brooklyn, New York, asked: "If they had an extended RVR [rapid virologic response], if they were negative for virus at week 4 and again at week 12, for which there was evidence in REALIZE, then perhaps they could get just 24 weeks of treatment. That's called response-guided therapy."

Dr. Bernstein's reasoning is that in patients without cirrhosis, an extended RVR is indicative of a greater than 90% SVR rate.

"The current recommendation is to treat these patients for 48 weeks, whether they have an extended RVR or not. In this study, this is a special subgroup of patients — even a sub-subgroup — because it is not just cirrhotics, but cirrhotics who have not responded previously to treatment.... It may be feasible to stop [treatment] at 24 weeks if they have this very favorable RVR," he told Medscape Medical News. As phase 4 data accrue, evidence might support doing so.

Dr. Pol reports being a consultant for Bristol-Myers Squibb, Boehringer Ingelheim, Tibotec, Novartis, and Gilead; and receiving grants for research from Bristol-Meyers Squibb, Gilead, Roche, and Schering-Plough/Merck. Dr. Bernstein has disclosed no relevant financial relationships.

The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting. Abstract 31. Presented November 6, 2011.

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