Sustained virologic response rates with telaprevir by response after 4 weeks of lead-in therapy in patients with prior treatment failure

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• 作者：Graham R. Foster¹ ; ^{g.r.foster@qmul.ac.uk} ; Stefan Zeuzem² ; Pietro Andreone³ ; Stanislas Pol⁴ ; Eric J. Lawitz⁵ ; Moises Diago⁶ ; Stuart Roberts⁷ ; Paul J. Pockros⁸ ; Zobair Younossi⁹ ; Isabelle Lonjon-Domanec¹⁰ ; Sandra De Meyer¹¹ ; Don Luo¹² ; Shelley George¹³ ; Maria Beumont¹¹ ; Gaston Picchio¹²
• 关键词：HCV ; hepatitis C virus ; SVR ; sustained virologic response ; DAA ; direct-acting antiviral ; FDA ; Food and Drug Administration ; EMA ; European Medicines Agency ; SD ; standard deviation ; BMI ; body mass index
• 刊名：Journal of Hepatology
• 出版年：2013
• 出版时间：March, 2013
• 年：2013
• 卷：58
• 期：3
• 页码：488-494
• 全文大小：709 K

文摘

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Background & Aims

For hepatitis C virus (HCV)-infected patients who have not responded to previous PegIFN/ribavirin treatment, it is unclear whether subsequent direct-acting antiviral therapy outcomes are better predicted by prior treatment response or by on-treatment response to a PegIFN/ribavirin lead-in.

Methods

In REALIZE, treatment-experienced patients randomized to the lead-in telaprevir arm received 4 weeks of PegIFN-¦Á-2a (180 ¦Ìg/week) and ribavirin (1000-1200 mg/day), then 12 weeks of telaprevir (750 mg every 8 h) plus PegIFN-¦Á-2a/ribavirin, followed by 32 weeks of PegIFN-¦Á-2a/ribavirin. This subanalysis only included patients in the lead-in telaprevir arm with available week 4 on-treatment response data (n = 240).

Results

After 4 weeks of PegIFN/ribavirin, 90 % of relapsers, 60 % of partial responders, and 41 % of null responders in the lead-in telaprevir arm had ?1 log₁₀ HCV RNA reduction. Sustained virologic response (SVR) rates for telaprevir-treated patients with ?1 versus <1 log₁₀ HCV RNA reduction after the PegIFN/ribavirin lead-in were 94 % versus 62 % in relapsers, 59 % versus 56 % in partial responders and 54 % versus 15 % in null responders.

Conclusions

In prior relapsers and partial responders there is no apparent benefit of assessing response after a PegIFN/ribavirin lead-in with the aim of guiding telaprevir-based treatment. For patients known to be prior null responders, on-treatment response after a 4-week PegIFN/ribavirin lead-in may provide clinically useful prognostic information. However, withholding telaprevir-containing therapy in uncategorised treatment-experienced patient populations (i.e., that could include prior relapsers or partial responders), using response after a PegIFN/ribavirin lead-in could potentially exclude some patients with a high chance of SVR.