Details

Autor(en) / Beteiligte

• De Meyer, Sandra
• Dierynck, Inge
• Ghys, Anne
• Beumont, Maria
• Daems, Bjorn
• Van Baelen, Ben
• Sullivan, James C.
• Bartels, Douglas J.
• Kieffer, Tara L.
• Zeuzem, Stefan
• Picchio, Gaston

Titel

Characterization of telaprevir treatment outcomes and resistance in patients with prior treatment failure: Results from the REALIZE trial

Ist Teil von

• Hepatology (Baltimore, Md.), 2012-12, Vol.56 (6), p.2106-2115

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Erscheinungsjahr

2012

Quelle

Wiley-Blackwell Full Collection

Beschreibungen/Notizen

• 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)