Role of telaprevir plasma levels for predicting response to antiviral therapy in patients with hepatitis C virus genotype 1 infection.

Abstract

OBJECTIVE:

Telaprevir (TVR)-based triple therapy has substantially improved cure rates of hepatitis C virus (HCV) genotype 1 infection but side effects are frequent and often severe. Therefore, response predictors are needed for early identification of patients not responding to TVR-based triple therapy.

MATERIAL AND METHODS:

Forty-five patients (mean age: 54 ± 13 years; male gender: 60%; treatment-experienced: 82%; cirrhosis: 58%) with HCV genotype 1 infection were treated with a TVR-based triple-therapy regimen. TVR plasma levels were analyzed by liquid chromatography electrospray-ionization-tandem mass spectrometry at weeks 2, 4, 8, and 12 of antiviral therapy. On-treatment HCV RNA response was assessed at weeks 4, 12, and 24 by real-time polymerase chain reaction.

RESULTS:

An extended rapid virological response (eRVR) and sustained virological response (SVR) was achieved in 21 of 45 patients (47%) and 36 of 45 (80%) patients, respectively. Mean ± standard deviation TVR plasma levels at week 2 were 3.4 ± 0.2 log10 ng/ml and did not differ over time (when assessed at weeks 4, 8, and 12). TVR plasma levels at week 2 were significantly higher in patients who achieved an eRVR compared to those who did not achieve eRVR (3.5 ± 0.1 vs. 3.3 ± 0.2 log10 ng/ml; p = 0.003) but were neither associated with SVR nor with treatment-related anemia.

CONCLUSION:

TVR plasma levels are associated with on-treatment response but not with overall treatment efficacy. Given the high overall response rates to TVR-based triple therapy, our data suggest that TVR trough levels may not be a useful predictor of treatment response, and routine drug-level monitoring is not required.

• Authors: Harald Farnik, Nerea Ferreirós, Sandra Labocha, Gerd Geisslinger, Stefan Zeuzem, Christoph Sarrazin, Johannes Vermehren
• Journal: Scandinavian journal of gastroenterology (Scand J Gastroenterol) Vol. 49 Issue 12 Pg. 1473-9 (Dec 2014) ISSN: 1502-7708 [Electronic] England
• PMID: 25384840 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Antiviral Agents
• Interferon-alpha
• Oligopeptides
• Recombinant Proteins
• Polyethylene Glycols
• telaprevir
• peginterferon alfa-2a

Topics

• Adult
• Aged
• Antiviral Agents (blood, pharmacokinetics, therapeutic use)
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (genetics)
• Hepatitis C, Chronic (drug therapy, virology)
• Humans
• Interferon-alpha (therapeutic use)
• Logistic Models
• Male
• Middle Aged
• Oligopeptides (blood, pharmacokinetics, therapeutic use)
• Polyethylene Glycols (therapeutic use)
• Recombinant Proteins (therapeutic use)
• Treatment Outcome
• Viral Load