Journal article
Characterization of Telaprevir Treatment Outcomes and Resistance in Patients With Prior Treatment Failure: Results From the REALIZE Trial
Hepatology (Baltimore, Md.), Vol.56(6), pp.2106-2115
12/01/2012
DOI: 10.1002/hep.25962
PMID: 22806681
Abstract
In the Phase 3 REALIZE study, 662 genotype 1 hepatitis C virus (HCV)-infected patients with prior peginterferon/ribavirin treatment failure (including relapsers, partial, and null responders) were randomized to 12 weeks of telaprevir given immediately (T12/PR48) or following 4 weeks of peginterferon/ribavirin (lead-in T12/PR48), or 12 weeks of placebo (PR48), combined with a total of 48 weeks of peginterferon alfa-2a/ribavirin. Sustained virologic response (SVR) rates were 64% (T12/PR48), 66% (lead-in T12/PR48), and 17% (PR48). This analysis aimed to characterize treatment outcomes and viral variants emerging in telaprevir-treated patients not achieving SVR. HCV NS3.4A population sequencing was performed at baseline, during treatment, and follow-up. Telaprevir-resistant variants were classified into lower-level (3- to 25-fold 50% inhibitory concentration [IC50] increase: V36A/M, T54A/S, R155I/K/M/T, and A156S) and higher-level (>25-fold IC50 increase: V36M+R155K and A156T/V) resistance. Resistant variants were uncommon at baseline. Overall, 18% (52%, 19%, and 1% of prior null and partial responders and relapsers, respectively) of telaprevir-treated patients had on-treatment virologic failure, with no significant difference with or without a lead-in. Virologic failure during the telaprevir-treatment phase was predominantly associated with higher-level resistance; virologic failure during the peginterferon/ribavirin-treatment phase was associated with higher- or lower-level, or wildtype variants, depending on genotype. Relapse occurred in 9% of patients completing assigned treatment and was generally associated with lower-level resistant variants or wildtype. Resistant variants were no longer detectable by study end (median follow-up of 11 months) in 58% of non-SVR patients. Conclusion: In REALIZE, variants emerging in non-SVR, telaprevir-treated patients were similar irrespective of the use of a lead-in and were consistent with those previously reported. In most patients, resistant variants became undetectable over time. (HEPATOLOGY 2012;56:2106-2115)
Details
- Title: Subtitle
- Characterization of Telaprevir Treatment Outcomes and Resistance in Patients With Prior Treatment Failure: Results From the REALIZE Trial
- Creators
- Sandra De Meyer - JanssenInge Dierynck - JanssenAnne Ghys - JanssenMaria Beumont - JanssenBjorn Daems - JanssenBen Van Baelen - JanssenJames C. Sullivan - Vertex PharmaceuticalsDouglas J. Bartels - Vertex PharmaceuticalsTara L. Kieffer - Vertex PharmaceuticalsStefan Zeuzem - Goethe University FrankfurtGaston Picchio - Janssen
- Resource Type
- Journal article
- Publication Details
- Hepatology (Baltimore, Md.), Vol.56(6), pp.2106-2115
- Publisher
- Wiley
- DOI
- 10.1002/hep.25962
- PMID
- 22806681
- ISSN
- 0270-9139
- eISSN
- 1527-3350
- Number of pages
- 10
- Grant note
- Vertex Pharmaceuticals Janssen Pharmaceuticals; Johnson & Johnson; Johnson & Johnson USA; Janssen Biotech Inc
- Language
- English
- Date published
- 12/01/2012
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984284341202771
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