Limits...
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.

Show MeSH

Related in: MedlinePlus

Results of bayesian mixed treatment comparison for treatment-naïve patients. The upper node part indicates the treatment group [Node labels: A, standard treatment (Peg-IFN-α/RBV 48 weeks); B, fixed-length treatment (FLT) with long tail (TVR 12/24 weeks/Peg-IFN-α/RBV 48 weeks); C, FLT with short tail (TVR 12 weeks/Peg-IFN-α/RBV 24 weeks); D, response-guided treatment (RGT) with tail (TVR 12 weeks/Peg-IFN-α/RBV 24 and/or 24 weeks); E, RGT tail (TVR 12 weeks/Peg-IFN-α/RBV 12 or 36 weeks), the lower node part gives the median proportion of patients (in percent) with sustained virological response (SVR, credible 95% bayesian intervals in square brackets). The edges indicate comparisons with the arrowhead indicating the comparator (i.e. baseline). The odds ratio of the respective comparison is shown with credible 95-% intervals of the bayesian analysis in square brackets. Dashed lines (and red text color) indicate comparison that was not observed but only simulated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3852825&req=5

Figure 4: Results of bayesian mixed treatment comparison for treatment-naïve patients. The upper node part indicates the treatment group [Node labels: A, standard treatment (Peg-IFN-α/RBV 48 weeks); B, fixed-length treatment (FLT) with long tail (TVR 12/24 weeks/Peg-IFN-α/RBV 48 weeks); C, FLT with short tail (TVR 12 weeks/Peg-IFN-α/RBV 24 weeks); D, response-guided treatment (RGT) with tail (TVR 12 weeks/Peg-IFN-α/RBV 24 and/or 24 weeks); E, RGT tail (TVR 12 weeks/Peg-IFN-α/RBV 12 or 36 weeks), the lower node part gives the median proportion of patients (in percent) with sustained virological response (SVR, credible 95% bayesian intervals in square brackets). The edges indicate comparisons with the arrowhead indicating the comparator (i.e. baseline). The odds ratio of the respective comparison is shown with credible 95-% intervals of the bayesian analysis in square brackets. Dashed lines (and red text color) indicate comparison that was not observed but only simulated.

Mentions: The primary efficacy endpoint (Figure 4) SVR, was reached significantly more often in the two FLT TVR regimens (75% [CrI 53 to 87%] in group B, 72% [CrI 50 to 87%] in group C) and in the long RGT triple regimen (group D: 75% [CrI 53 to 88%]) compared to standard treatment (group A: 46% [CrI 27 to 67%]). There was no significant difference for the short RGT TVR regimen (group E: 57% [CrI 32 to 78%]) compared to the standard treatment. Comparison of the TVR regimens shows that there was no significant difference between the two FLT regimens and the long RGT treatment. All three were found to be superior to the short RGT regimen. This result implies that the long RGT regimen is not inferior to a 48 weeks FLT regimen (OR of group D vs. B: 1 [CrI 0.6 to 1.5]). Furthermore, the long RGT regimen and the 48 weeks FLT regimen were not superior to the 24 weeks FLT (OR of group B vs. C 1.2 [CrI 0.8 to 1.9] and D vs. C 1.2 [CrI 0.7 to 1.9]).


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)

Results of bayesian mixed treatment comparison for treatment-naïve patients. The upper node part indicates the treatment group [Node labels: A, standard treatment (Peg-IFN-α/RBV 48 weeks); B, fixed-length treatment (FLT) with long tail (TVR 12/24 weeks/Peg-IFN-α/RBV 48 weeks); C, FLT with short tail (TVR 12 weeks/Peg-IFN-α/RBV 24 weeks); D, response-guided treatment (RGT) with tail (TVR 12 weeks/Peg-IFN-α/RBV 24 and/or 24 weeks); E, RGT tail (TVR 12 weeks/Peg-IFN-α/RBV 12 or 36 weeks), the lower node part gives the median proportion of patients (in percent) with sustained virological response (SVR, credible 95% bayesian intervals in square brackets). The edges indicate comparisons with the arrowhead indicating the comparator (i.e. baseline). The odds ratio of the respective comparison is shown with credible 95-% intervals of the bayesian analysis in square brackets. Dashed lines (and red text color) indicate comparison that was not observed but only simulated.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Results of bayesian mixed treatment comparison for treatment-naïve patients. The upper node part indicates the treatment group [Node labels: A, standard treatment (Peg-IFN-α/RBV 48 weeks); B, fixed-length treatment (FLT) with long tail (TVR 12/24 weeks/Peg-IFN-α/RBV 48 weeks); C, FLT with short tail (TVR 12 weeks/Peg-IFN-α/RBV 24 weeks); D, response-guided treatment (RGT) with tail (TVR 12 weeks/Peg-IFN-α/RBV 24 and/or 24 weeks); E, RGT tail (TVR 12 weeks/Peg-IFN-α/RBV 12 or 36 weeks), the lower node part gives the median proportion of patients (in percent) with sustained virological response (SVR, credible 95% bayesian intervals in square brackets). The edges indicate comparisons with the arrowhead indicating the comparator (i.e. baseline). The odds ratio of the respective comparison is shown with credible 95-% intervals of the bayesian analysis in square brackets. Dashed lines (and red text color) indicate comparison that was not observed but only simulated.
Mentions: The primary efficacy endpoint (Figure 4) SVR, was reached significantly more often in the two FLT TVR regimens (75% [CrI 53 to 87%] in group B, 72% [CrI 50 to 87%] in group C) and in the long RGT triple regimen (group D: 75% [CrI 53 to 88%]) compared to standard treatment (group A: 46% [CrI 27 to 67%]). There was no significant difference for the short RGT TVR regimen (group E: 57% [CrI 32 to 78%]) compared to the standard treatment. Comparison of the TVR regimens shows that there was no significant difference between the two FLT regimens and the long RGT treatment. All three were found to be superior to the short RGT regimen. This result implies that the long RGT regimen is not inferior to a 48 weeks FLT regimen (OR of group D vs. B: 1 [CrI 0.6 to 1.5]). Furthermore, the long RGT regimen and the 48 weeks FLT regimen were not superior to the 24 weeks FLT (OR of group B vs. C 1.2 [CrI 0.8 to 1.9] and D vs. C 1.2 [CrI 0.7 to 1.9]).

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