Characterization of telaprevir treatment outcomes and resistance in patients with prior treatment failure : results from the REALIZE trial
Copyright © 2012 American Association for the Study of Liver Diseases..
UNLABELLED: 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 [IC(50) ] increase: V36A/M, T54A/S, R155I/K/M/T, and A156S) and higher-level (>25-fold IC(50) 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2012 |
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| Erschienen: |
2012 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:56 |
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| Enthalten in: |
Hepatology (Baltimore, Md.) - 56(2012), 6 vom: 15. Dez., Seite 2106-15 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
De Meyer, Sandra [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.02.2013 Date Revised 02.12.2018 published: Print Citation Status MEDLINE |
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| doi: |
10.1002/hep.25962 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM219511306 |
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| 100 | 1 | |a De Meyer, Sandra |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Characterization of telaprevir treatment outcomes and resistance in patients with prior treatment failure |b results from the REALIZE trial |
| 264 | 1 | |c 2012 | |
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| 500 | |a Date Completed 28.02.2013 | ||
| 500 | |a Date Revised 02.12.2018 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2012 American Association for the Study of Liver Diseases. | ||
| 520 | |a UNLABELLED: 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 [IC(50) ] increase: V36A/M, T54A/S, R155I/K/M/T, and A156S) and higher-level (>25-fold IC(50) 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Interferon-alpha |2 NLM | |
| 650 | 7 | |a Oligopeptides |2 NLM | |
| 650 | 7 | |a RNA, Viral |2 NLM | |
| 650 | 7 | |a Recombinant Proteins |2 NLM | |
| 650 | 7 | |a Polyethylene Glycols |2 NLM | |
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| 650 | 7 | |a Ribavirin |2 NLM | |
| 650 | 7 | |a 49717AWG6K |2 NLM | |
| 650 | 7 | |a telaprevir |2 NLM | |
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| 700 | 1 | |a Dierynck, Inge |e verfasserin |4 aut | |
| 700 | 1 | |a Ghys, Anne |e verfasserin |4 aut | |
| 700 | 1 | |a Beumont, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Daems, Bjorn |e verfasserin |4 aut | |
| 700 | 1 | |a Van Baelen, Ben |e verfasserin |4 aut | |
| 700 | 1 | |a Sullivan, James C |e verfasserin |4 aut | |
| 700 | 1 | |a Bartels, Douglas J |e verfasserin |4 aut | |
| 700 | 1 | |a Kieffer, Tara L |e verfasserin |4 aut | |
| 700 | 1 | |a Zeuzem, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Picchio, Gaston |e verfasserin |4 aut | |
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