Provided by Healio
June 20, 2013
Nearly all patients with chronic hepatitis C who achieved sustained virologic response to therapy with pegylated interferon, ribavirin and direct-acting antivirals continued to have undetectable HCV RNA over long-term follow-up in a recent study.
Researchers followed 103 white patients with chronic HCV who had participated in randomized, controlled trials or an extended access program in which they achieved sustained virologic response (SVR) at 24 weeks after completing combination therapy with peginterferon alfa-2a and ribavirin and a direct-acting antiviral (DAA). Evaluated DAAs included protease inhibitors (90.3% of cases), NS5B polymerase inhibitors (6.8%) and both in combination (2.9%). Patients were followed for a median of 21 months after achieving SVR (range 7 to 64 months).
The cohort included 80 treatment-naive patients, 17 who had been nonresponsive and six who had relapsed during prior therapy. Nearly all patients were infected with HCV genotype 1, including 34 with genotype 1a and 67 with 1b, while two patients had genotype 4.
Relapse occurred in two patients who had genotype 1b and had been treated with faldaprevir. Both patients achieved undetectable HCV RNA levels at 4 weeks, and cloning sequencing after relapse indicated identical sequences to those observed at baseline. Viral resistance was unseen in either case.
One treatment-naive, noncirrhotic woman who relapsed had detectable HCV RNA 8 months after therapy cessation, which increased to pretreatment levels in subsequent months. Retreatment with 24 weeks of peginterferon, ribavirin and telaprevir resulted in undetectable RNA levels. The second relapser, a treatment-naive cirrhotic man, had detectable HCV RNA 12 months after therapy ended that returned to pretreatment levels shortly after detection.
“To the best of our knowledge, this is the first study reporting long-term virological outcomes in patients with hepatitis C after successful antiviral triple therapy,” the researchers wrote. “Our study shows that HCV eradication by triple therapy remains durable and confirms an excellent long-term prognosis of HCV patients with SVR. To assess the long-term clinical benefit of triple therapy, studies with a longer follow-up and larger patient numbers are needed.”
Disclosure: See the study for a full list of relevant disclosures.
Sustained virological response, historically, has been tantamount to a cure in patients who are treated for hepatitis C. The problem, of course, is that with every change in therapy, it's necessary to validate that the concept of SVR - no virus detectable in the blood 6 months after stopping treatment - actually applies. It applies for pegylated interferon and ribavirin, and now we're seeing evidence that it also applies when we're using direct-acting antiviral agents in addition.
[This is] an important study to do. I think the strength of it is that it has at least a moderate number of patients, over 100, and they found, not surprisingly, that SVR 24 weeks after stopping treatment seems to be associated with permanent eradication of detectable virus. Again, this is not surprising, but still an important detail that needs to be hammered out, and the study goes a long way toward doing that.
The limitations of the study are that they looked at many different direct-acting agents, and so the number of patients treated with any particular direct-acting agent is somewhat limited. This really comes into focus when we look at the two breakthrough patients: They were both treated with the same drug. So [the study] raises, but doesn't answer the question: "Is faldaprevir different than the other agents that were tested?" It's really impossible to say, because the numbers are too small, but it raises the question of whether this agent is going to be associated with a higher rate of breakthrough than the other agents tested here.
Instead of 100 patients, I'd like to see 1,000, and certainly there are many many hundreds of patients who have been in randomized trials, and this data is or will soon become available. So I think that this is a good beginning, but we just need to see larger numbers, and we need to see numbers that are specific to each and every direct-acting antiviral drug.
William Carey, MD
Professor of medicine, Cleveland Clinic Liver College of Medicine
Founding member, Cleveland Clinic Hepatology section
Disclosures: Dr. Carey reported no relevant financial disclosures.