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EASL 2013: Anemia Is a Common Side Effect of First-generation HCV Protease Inhibitors

About half of patients taking boceprevir (Victrelis) or telaprevir (Incivek or Incivo) developed anemia and approximately one-third experienced skin rash, but sustained response rates were high in an analysis of a population representative of people with chronic hepatitis C in North America, researchers reported at the EASL International Liver Congress (EASL 2013) last month in Amsterdam.

Treatment response rates were generally high in Phase 3 pivotal trials supporting approval of the first 2 HCV protease inhibitors, but clinical studies often include an easier-to-treat population than the range of patients who will need to be treated in the "real world."

Michael Fried from the University of North Carolina at Chapel Hill and fellow investigators with the HCV-TARGET consortium evaluated the safety and efficacy of triple therapy using boceprevir or telaprevir plus pegylated interferon and ribavirin in a broad population including patients under-represented in clinical trials. The consortium used standardized data abstraction and a common database to enable consistent data collection.

HCV-TARGET enrolled 1919 participants at 44 academic and 59 community medical centers in the U.S. and Canada. A total of 1457 people were included in the current analysis. About 60% were men, 72% were white, and 21% were black. The mean age was 62 years, with 80% were in the 40 to 64 year age range. Just under 60% had harder-to-treat HCV genotype 1a and nearly 40% (n=550) had cirrhosis -- substantially more than in Phase 3 trials.

Participants were evenly divided between treatment-naive and treatment-experienced. About three-quarters used telaprevir, the rest boceprevir. About half (46%) were still on treatment but had passed 16 weeks, 6% had less than 16 weeks on treatment, and 22% had completed a full course of triple therapy.

Results

• Virological response rates after 12 weeks on treatment were 91%-96% for telaprevir recipients and 63%-87% for boceprevir recipients, with previously untreated patients doing better than prior non-responders.
• 23% of participants discontinued treatment early: 8% due to lack of efficacy, 9% due to adverse events, 5% for other reasons, and 2% for multiple reasons.
• Side effects were common, with 80% of telaprevir recipients and 71% of boceprevir recipients experiencing any adverse events:

o   62% and 54%, respectively, developed anemia;

o   51% and 24%, respectively, experienced any rash;

o   29% and 4% experienced anorectal symptoms such as itching.

• 10% of participants taking either protease inhibitor experienced serious adverse events.
• Looking at both drugs combined, people with cirrhosis were more likely to develop anemia (22% vs 14% of non-cirrhotics) and to stop treatment due to adverse events (12% vs 7%).
• Anemia was most commonly managed with ribavirin dose reduction rather than erythropoietin (EPO) or blood transfusion.
• 11% of patients with cirrhosis experienced liver decompensation (ascites, hepatic encephalopathy, bleeding varices), including 2 who died from sepsis.

"In this interim analysis, the safety and on-treatment efficacy of telaprevir and boceprevir in the real-world setting are comparable to that observed in registration trials," the investigators concluded. "Although no new safety signals were observed, anemia emerged as the most relevant adverse event impacting clinical care."

5/15/13

Reference

MW Fried, KRReddy, AM Di Bisceglie, et al. HCV-TARGET: a longitudinal, observational study of North American patients with chronic hepatitis C (HCV) treated with boceprevir or telaprevir. 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013). Amsterdam. April 24-28, 2013. Abstract 818.