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Treatment of chronic HCV genotype 1 infection with telaprevir: a Bayesian mixed treatment comparison of fixed-length and response-guided treatment regimens in treatment-naïve and -experienced patients.

Goralczyk AD, Cameron S, Amanzada A - BMC Gastroenterol (2013)

Bottom Line: In RGT-regimens patients that did not achieve extended rapid-virological-response (eRVR) within the first 4-12 weeks undergo treatment for 48-weeks, whereas in fixed-length-treatment (FLT) patients are treated for a fixed-duration regardless of their RVR.Patients treated with short RGT (simulated group E) did also have a significant improvement when they were treatment-experienced (simulated OR 3.6 (CrI 1.6-8.2)), whereas the effect was not significant in treatment-naïve patients (OR E vs.A 1.6 (CrI 0.9-2.7)).

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Gastroenterology and Endocrinology, University Medical Center Goettingen, Georg-August-University Goettingen, Goettingen, Germany. ahmad.amanzada@med.uni-goettingen.de.

ABSTRACT

Background: Telaprevir (TVR) has been approved for response-guided-therapy (RGT) of chronic hepatitis C (HCV) genotype-1-infection in treatment-naïve and -experienced patients. In RGT-regimens patients that did not achieve extended rapid-virological-response (eRVR) within the first 4-12 weeks undergo treatment for 48-weeks, whereas in fixed-length-treatment (FLT) patients are treated for a fixed-duration regardless of their RVR.

Methods: This systematic review and Bayesian mixed-treatment-comparison (MTC) aimed to compare the efficacy and safety of standard-therapy with pegylated-interferon-α/ribavirin (Peg-IFN-α/RBV (48 weeks), group A), FLT with TVR, Peg-IFN-α/RBV for 12 weeks with a long (+36 weeks, group B) or short (+12 weeks, group C) tail of Peg-IFN-α/RBV treatment, and RGT with 12 weeks of TVR, Peg-IFN-α/RBV followed by 12 weeks of Peg-IFN-α/RBV (group D) or no therapy (group E).

Results: We identified seven randomized controlled trials including 3505 patients. Compared to standard-treatment (group A), treatment-naïve patients allocated to groups B, C, and D were significantly more likely to achieve sustained-virological-response (SVR, odds ratios (OR): B vs. A 3.5 (credibility interval [CrI] 2.2-5.4), C vs. A 3.0 (CrI 1.8-4.9), D vs. A 3.4 (CrI 2.5-4.6)). Treatment-experienced patients achieved increased SVR rates when they were treated in group B (OR: 8.2 (CrI 5.0-13.5)), C (OR 7.0 (CrI 3.9-12.8)), or simulated group D (OR 8.2 (CrI 4.3-15.3)). Patients treated with short RGT (simulated group E) did also have a significant improvement when they were treatment-experienced (simulated OR 3.6 (CrI 1.6-8.2)), whereas the effect was not significant in treatment-naïve patients (OR E vs. A 1.6 (CrI 0.9-2.7)).

Conclusion: Long FLT and RGT regimens are useful treatment options for HCV-genotype-1 in both treatment-naïve and -experienced patients. A short 24-weeks FLT regimen does not seem to be inferior and should further be evaluated in clinical trials to reduce side effects and costs of treatment.

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Treatment regimens; TVR: telaprevir; IFN: pegylated interferon-α; RBV: ribavirin.
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Figure 1: Treatment regimens; TVR: telaprevir; IFN: pegylated interferon-α; RBV: ribavirin.

Mentions: Additionally, included trials had to report results on at least two of the following five treatment groups (Figure 1): (A) standard treatment with Peg-IFN-α and RBV for 48 weeks; (B) FLT with either 12 weeks of TVR in combination with Peg-IFN-α and RBV followed by 36 weeks of treatment with Peg-IFN-α and RBV or 24 weeks of treatment with TVR, Peg-IFN-α, and RBV followed by 24 weeks of Peg-IFN-α and RBV (overall treatment duration 48 weeks); (C) 12 weeks of TVR in combination with Peg-IFN-α and RBV followed by 12 weeks of treatment with Peg-IFN-α and RBV (overall treatment duration 24 weeks); (D) RGT with 12 weeks of TVR, Peg-IFN-α and RBV followed by 12 weeks of treatment with Peg-IFN-α and RBV for patients that had eRVR and 36 weeks of treatment for patients that had no eRVR; (E) RGT with 12 weeks of TVR, Peg-IFN-α and RBV followed by no further treatment for patients that had eRVR or 36 weeks of treatment with Peg-IFN-α and RBV for patients that had no eRVR. Treatment arms in which patients received no RBV or a treatment duration with TVR that was less than 12 weeks duration were excluded.


Treatment of chronic HCV genotype 1 infection with telaprevir: a Bayesian mixed treatment comparison of fixed-length and response-guided treatment regimens in treatment-naïve and -experienced patients.

Goralczyk AD, Cameron S, Amanzada A - BMC Gastroenterol (2013)

Treatment regimens; TVR: telaprevir; IFN: pegylated interferon-α; RBV: ribavirin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3852825&req=5

Figure 1: Treatment regimens; TVR: telaprevir; IFN: pegylated interferon-α; RBV: ribavirin.
Mentions: Additionally, included trials had to report results on at least two of the following five treatment groups (Figure 1): (A) standard treatment with Peg-IFN-α and RBV for 48 weeks; (B) FLT with either 12 weeks of TVR in combination with Peg-IFN-α and RBV followed by 36 weeks of treatment with Peg-IFN-α and RBV or 24 weeks of treatment with TVR, Peg-IFN-α, and RBV followed by 24 weeks of Peg-IFN-α and RBV (overall treatment duration 48 weeks); (C) 12 weeks of TVR in combination with Peg-IFN-α and RBV followed by 12 weeks of treatment with Peg-IFN-α and RBV (overall treatment duration 24 weeks); (D) RGT with 12 weeks of TVR, Peg-IFN-α and RBV followed by 12 weeks of treatment with Peg-IFN-α and RBV for patients that had eRVR and 36 weeks of treatment for patients that had no eRVR; (E) RGT with 12 weeks of TVR, Peg-IFN-α and RBV followed by no further treatment for patients that had eRVR or 36 weeks of treatment with Peg-IFN-α and RBV for patients that had no eRVR. Treatment arms in which patients received no RBV or a treatment duration with TVR that was less than 12 weeks duration were excluded.

Bottom Line: In RGT-regimens patients that did not achieve extended rapid-virological-response (eRVR) within the first 4-12 weeks undergo treatment for 48-weeks, whereas in fixed-length-treatment (FLT) patients are treated for a fixed-duration regardless of their RVR.Patients treated with short RGT (simulated group E) did also have a significant improvement when they were treatment-experienced (simulated OR 3.6 (CrI 1.6-8.2)), whereas the effect was not significant in treatment-naïve patients (OR E vs.A 1.6 (CrI 0.9-2.7)).

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Gastroenterology and Endocrinology, University Medical Center Goettingen, Georg-August-University Goettingen, Goettingen, Germany. ahmad.amanzada@med.uni-goettingen.de.

ABSTRACT

Background: Telaprevir (TVR) has been approved for response-guided-therapy (RGT) of chronic hepatitis C (HCV) genotype-1-infection in treatment-naïve and -experienced patients. In RGT-regimens patients that did not achieve extended rapid-virological-response (eRVR) within the first 4-12 weeks undergo treatment for 48-weeks, whereas in fixed-length-treatment (FLT) patients are treated for a fixed-duration regardless of their RVR.

Methods: This systematic review and Bayesian mixed-treatment-comparison (MTC) aimed to compare the efficacy and safety of standard-therapy with pegylated-interferon-α/ribavirin (Peg-IFN-α/RBV (48 weeks), group A), FLT with TVR, Peg-IFN-α/RBV for 12 weeks with a long (+36 weeks, group B) or short (+12 weeks, group C) tail of Peg-IFN-α/RBV treatment, and RGT with 12 weeks of TVR, Peg-IFN-α/RBV followed by 12 weeks of Peg-IFN-α/RBV (group D) or no therapy (group E).

Results: We identified seven randomized controlled trials including 3505 patients. Compared to standard-treatment (group A), treatment-naïve patients allocated to groups B, C, and D were significantly more likely to achieve sustained-virological-response (SVR, odds ratios (OR): B vs. A 3.5 (credibility interval [CrI] 2.2-5.4), C vs. A 3.0 (CrI 1.8-4.9), D vs. A 3.4 (CrI 2.5-4.6)). Treatment-experienced patients achieved increased SVR rates when they were treated in group B (OR: 8.2 (CrI 5.0-13.5)), C (OR 7.0 (CrI 3.9-12.8)), or simulated group D (OR 8.2 (CrI 4.3-15.3)). Patients treated with short RGT (simulated group E) did also have a significant improvement when they were treatment-experienced (simulated OR 3.6 (CrI 1.6-8.2)), whereas the effect was not significant in treatment-naïve patients (OR E vs. A 1.6 (CrI 0.9-2.7)).

Conclusion: Long FLT and RGT regimens are useful treatment options for HCV-genotype-1 in both treatment-naïve and -experienced patients. A short 24-weeks FLT regimen does not seem to be inferior and should further be evaluated in clinical trials to reduce side effects and costs of treatment.

Show MeSH
Related in: MedlinePlus