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ICAAC 2014: Telaprevir and Boceprevir Have Limited Efficacy in Real-world Use


Hepatitis C treatment using the first-generation HCV protease inhibitors telaprevir (Incivek or Incivo) or boceprevir (Victrelis) cured only 71% of people with easier-to-treat HCV genotypes 1b, falling to 47% for those with genotype 1a, researchers reported at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy this month in Washington, DC.

The advent of direct-acting antivirals (DAAs) that target different steps of the HCV lifecycle has brought about a revolution in treatment. The first 2 approved DAAs, boceprevir and telaprevir, had to be used with pegylated interferon and ribavirin. While they produced higher rates of post-treatment sustained virological response (SVR) than pegylated interferon/ribavirin alone -- about 65% and 75%, respectively, for previously untreated patients -- they were inconvenient to take and added their own side effects (most prominently skin rash and anemia).

Gil Ben Yakov and colleagues conducted a study of real-world outcomes among chronic hepatitis C patients treated at Soroka Medical Center in Beer Sheva -- the largest medical center in southern Israel, which serves a population of over 1 million and manages the vast majority of hepatitis C cases in the region. The center started treating people with HCV genotype 1 using the first-generation DAAs, especially after they were included as a treatment option by the national health care system.

This retrospective analysis included 55 hepatitis C patients treated with triple therapy in the outpatient liver clinic between September 2011 and November 2013 and completed a 6-month period of post treatment follow-up, allowing researchers to evaluate SVR24, or continued undetectable HCV RNA at 24 weeks after finishing therapy. About 70% (39 patients) used telaprevir while 16 used boceprevir.


  • Overall, 34 of 55 patients, or 62%, achieved SVR.
  • SVR rates were 47% for people with harder-to-treat HCV genotype 1a and 71% for those with genotype 1b.
  • SVR rates were similar for people with absent to moderate liver fibrosis (stage F0-F2) and those with advanced fibrosis or cirrhosis (F3-F4), at 64% and 63%, respectively.
  • SVR rates were 57% for treatment-naive patients, 83% for prior relapsers (who responded well during previous treatment but relapsed during follow-up), and 57% for prior non-responders to interferon/ribavirin.

These response rates are considerably lower than SVR rates in the 80%-90% range seen in clinical trials of newer DAAs added to pegylated interferon/ribavirin, and in the 90%-100% range for next-generation DAAs in interferon-free regimens. The new drugs are also easier to take, better tolerated, and allow for shorter treatment.

"In our experience, [protease inhibitor]-based triple [therapy] for HCV genotype 1, though more effective than previous dual treatment, is still limited in effectiveness and holds major safety issues," the researchers concluded. "In light of the era where new, much more effective and safe DAAs begin to emerge, the triple therapy in our view should be given mainly to patients with advanced disease [who] cannot wait for the new drugs to be available and affordable."

Ben Yakov suggested that triple therapy using the older DAAs might continue to be used in resource-limited countries that cannot afford the higher cost of the newer drugs. However, eliminating interferon, shortening treatment, and not having to manage side effects could make the new therapies cost-effective.



G Ben Yakov, D Montano, A Abu Freha, et al. Triple Therapy for HCV Genotype 1 - Real Life Experience in a Referral Center in Southern Israel. 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2014). Washington, DC, September 5-9, 2014. Abstract V-479.