Triple Therapy Can Help in Advanced Hep C

By Michael Smith, North American Correspondent, MedPage Today

Published: April 28, 2013

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

AMSTERDAM -- About 40% of people with advanced hepatitis C (HCV) can benefit from triple therapy even if they have cirrhosis and previous treatment failures, a researcher said here.

An interim analysis of a large cohort of patients in France found that benefit following treatment with one of the recently approved HCV protease inhibitors, telaprevir (Incivek) or boceprevir (Victrelis), when each was combined with pegylated interferon and ribavirin, according to Helene Fontaine, MD, of Cochin Hospital AP-HP in Paris.

But the benefit was counterbalanced by a high risk of serious adverse events, Fontaine reported at the meeting of the European Association for the Study of the Liver (EASL).

Triple therapy has been shown to improve outcomes for most HCV patients, commented Laurent Castera, MD, PhD, of Centre Hospitalier Universitaire in Bordeaux, France, who was not involved in the study but who moderated an EASL press conference.

But it's not well understood how very sick patients will respond to treatment because they have been largely left out of clinical trials, he said, and those who have been treated have generally had poor outcomes.

"The paradox is that for the patients who most need treatment – patients with cirrhosis and treatment-experienced patients – results have been pretty disappointing," he said.

The current study, which is from the French early access program, may go some way toward clarifying what can be expected from triple therapy in very sick patients, he said.

The CUPIC study (for Compassionate Use of Protease Inhibitors in viral C Cirrhosis) now includes some 674 cirrhotic or treatment-experienced patients treated at 56 sites from Feb. 15, 2011 to April 12, 2013.

The primary endpoint is the rate of undetectable HCV RNA 24 weeks after the end of the therapy (SVR₂₄). But since many patients have not reached that mark, Fontaine reported SVR₁₂ data for 485 patients, or 72% of the cohort.

In that subgroup, 295 patients were treated with telaprevir (Incivek) and 190 with boceprevir (Victrelis), both combined with pegylated interferon and ribavirin, Fontaine said. The study is observational, with no randomization, and the treatment choice is left to the patient and his or her doctor, she noted.

Response rates – defined as undetectable HCV viremia -- in the telaprevir patients reached a high of 81% at week 12 of treatment, but then tailed off to 56% at week 48, the end of treatment, Fontaine said.

Twelve weeks later, 40% of patients still had undetectable HCV RNA and had achieved an SVR₁₂.

The pattern among the boceprevir patients was "not different," Fontaine said – the response rates peaked during therapy, fell to 57% at the end of treatment, and 41% of patients achieved SVR₁₂.

In either case, patients who had previously responded to treatment pegylated interferon and ribavirin but then relapsed did better, with SVR₁₂ rates of 53% for telaprevir and 51% for boceprevir, than those who had never responded or had a partial response.

In addition, patients with the HCV 1a genotype did worse than those with genotype 1b, regardless of the protease inhibitor.

A multivariate analysis found that patients who relapsed had an odds ratio for SVR₁₂ of 2.03 (95% CI 1.38 to 3.0) compared with null or partial responders (P=0.0003).

The analysis also showed that genotype 1b patients had an OR for SVR₁₂ of 1.92 (95% CI 1.3 to 2.84) compared with genotype 1a (P=0.0011).

On the other hand, Fontaine said, rates of serious adverse events were high in both groups.

Among telaprevir patients, there were 535 serious adverse events among 160 patients while 63 patients stopped treatment because of serious adverse events. There were seven deaths.

The researchers noted that 9.1% of patients had severe infections and 12.9% had severe anemia. Anemia of 8 g/dL or blood transfusion was reported in 17.8% of cases.

Among boceprevir patients, the pattern was similar: There were 321 serious adverse events among 97 patients and 27 patients stopped treatment because of serious adverse events. There were three deaths.

Also, 4.2% of patients had severe infections and 10% had severe anemia. Anemia of less than 8 g/dL or blood transfusion was reported in 8.7% of cases.

She concluded that while some patients – especially those who had relapsed after previous therapy and those with genotype 1b disease – can do well on triple therapy, the benefit "should be balanced" with the risks of serious adverse events.

The study was supported by ANRS. Fontaine reported financial links with Jannsen, BMS, MSD, Roche, and Gilead.

Castera reported financial links with BMS, Merck, Gilead, and Echosens.

Primary source: European Association for the Study of the Liver
Source reference:
Fontaine H, et al. "SVR12 Rates and Safety of Triple Therapy Including Telaprevir or Boceprevir in 221 Cirrhotic Non-Responders Treated in the Frent Early Access Program (ANRS CO20-CUPIC)." EASL 20113;abstract 60.

Source