Multicenter prospective study to optimize the efficacy of triple therapy with telaprevir in patients with genotype 1b hepatitis C virus infection according to an algorithm based on the drug Adherence, IL‐28B Gene Allele and Viral Response Trial (AG &amp; RGT)

Sugawara, Kayoko; Koushima, Youhei; Inao, Mie; Nakayama, Nobuaki; Nagoshi, Sumiko; Yakabi, Koji; Tamano, Masaya; Asabe, Shinichi; Nishikawa, Ko; Harada, Youji; Sekine, Chuichi; Fukuya, Yuji; Funyu, Junji; Hashimoto, Yoshiaki; Mochida, Satoshi

doi:10.1111/hepr.12475

Cited by 4 publications

(3 citation statements)

References 18 publications

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“…Cirrhotic patients were included in the CUPIC cohort if they had prior failure of treatment with interferon with or without ribavirin. Prior response to antiviral therapy has been shown to be a strong predictive factor of SVR under triple therapy , a finding that our study confirms for the particular subset of cirrhotic patients. However, information on prior treatment response is nonexistent in naïve patients.…”

Section: Discussionsupporting

confidence: 83%

The CUPIC algorithm: an accurate model for the prediction of sustained viral response under telaprevir or boceprevir triple therapy in cirrhotic patients

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Ducancelle

Vergniol

et al. 2015

Journal of Viral Hepatitis

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Triple therapy using boceprevir or telaprevir remains the reference treatment for genotype 1 chronic hepatitis C in countries where new interferon-free regimens have not yet become available. Antiviral treatment is highly required in cirrhotic patients, but they represent a difficult-to-treat population. We aimed to develop a simple algorithm for the prediction of sustained viral response (SVR) in cirrhotic patients treated with triple therapy. A total of 484 cirrhotic patients from the ANRS CO20 CUPIC cohort treated with triple therapy were randomly distributed into derivation and validation sets. A total of 52.1% of patients achieved SVR. In the derivation set, a D0 score for the prediction of SVR before treatment initiation included the following independent predictors collected at day 0: prior treatment response, gamma-GT, platelets, telaprevir treatment, viral load. To refine the prediction at the early phase of the treatment, a W4 score included as additional parameter the viral load collected at week 4. The D0 and W4 scores were combined in the CUPIC algorithm defining three subgroups: 'no treatment initiation or early stop at week 4', 'undetermined' and 'SVR highly probable'. In the validation set, the rates of SVR in these three subgroups were, respectively, 11.1%, 50.0% and 82.2% (P < 0.001). By replacing the variable 'prior treatment response' with 'IL28B genotype', another algorithm was derived for treatment-naïve patients with similar results. The CUPIC algorithm is an easy-to-use tool that helps physicians weigh their decision between immediately treating cirrhotic patients using boceprevir/telaprevir triple therapy or waiting for new drugs to become available in their country.

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Section: Discussionsupporting

confidence: 83%

The CUPIC algorithm: an accurate model for the prediction of sustained viral response under telaprevir or boceprevir triple therapy in cirrhotic patients

Boursier

Ducancelle

Vergniol

et al. 2015

Journal of Viral Hepatitis

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“…In our previous trial to optimize the efficacy of triple therapy with telaprevir in patients infected with genotype 1b HCV [16], a history of previous Peg-IFN plus ribavirin therapies, IL28B-related gene SNPs, telaprevir adherence, virologic response during the therapy, and the period of Peg-IFN plus ribavirin administrations were identified as significant factors associated with SVR achievement. For dual oral therapy with daclatasvir plus asunaprevir, however, none of these factors were associated with SVR achievement, while resistanceassociated variants (RAVs) to daclatasvir were shown to be crucial for the development of virologic failure during and after treatment [14,15,17]: an SVR was obtained in 91.3 % of patients with NS5A-Y93 wild-type HCV strains at baseline, while the SVR rate was 43.3 % among those with pre-existing HCV strains showing NS5A-Y93H mutation [15].…”

Section: Introductionmentioning

confidence: 99%

Significance of variants associated with resistance to NS5A inhibitors in Japanese patients with genotype 1b hepatitis C virus infection as evaluated using cycling-probe real-time PCR combined with direct sequencing

et al. 2015

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“…A recent study showed that in patients who become negative for HCV RNA at or after 12 weeks of treatment, the rate of complete response can be improved by the use of PEG-IFN/RBV combination therapy for 72 weeks ( 18 ). Although further studies with a larger sample size are required, the use of the highly sensitive HCV-RNA quantitative assay may improve the prediction of therapeutic outcomes.…”

Section: Discussionmentioning

confidence: 99%

Clinical efficacy of the highly sensitive hepatitis C virus RNA quantitative assay in patients with relapse following interferon-based therapy with second-generation direct-acting antivirals

et al. 2016

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For refractory chronic hepatitis C, interferon (IFN)-based triple-agent combination therapy with second-generation direct-acting antivirals (DAAs) has been established as the standard treatment method. The rate of decrease in the viral load and the negative conversion of hepatitis C virus (HCV) RNA in the early phase following treatment initiation are considered important factors for predicting the therapeutic outcome. In the present study, the Roche Cobas AmpliPrep/COBAS TaqMan (CAP/CTM) HCV v2.0 assay and the AccuGENE m-HCV RNA quantitative assay [Abbott RealTime HCV (ART) assay] were analyzed for their clinical efficacy and ability to predict therapeutic outcomes in the early phase in patients with relapse following IFN-based second-generation DAA therapy. Of the 56 patients who received IFN-based second-generation DAA therapy since December 2013, 6 achieved an end-of-treatment response (ETR), but subsequently experienced relapse. In these 6 patients, fluctuations in viral loads in the early phase detected by the CAP/CTM and ART assays were compared. At 4 weeks after treatment initiation, 4 of the 6 patients were diagnosed as negative by the CAP/CTM assay, whereas 2 of these 4 patients were not identified as negative by the ART assay. Of the 2 patients, one was signal-positive with an HCV RNA load <1.08 Log IU/ml, and the other patient had a viral load of 1.12 Log IU/ml. At 8 weeks after treatment initiation, 1 patient was found to be negative by the CAP/CTM assay, but signal-positive with a viral load <1.08 Log IU/ml by the ART assay. From 4 to 8 weeks after treatment initiation, 3 of the 6 patients appeared to be discrepant cases. In conclusion, of the 6 patients who achieved an ETR, 4 were determined to have achieved a rapid virological response (RVR) by the CAP/CTM assay, but may not have actually become negative. The ART assay is highly sensitive, has a wide measurement range, may be suitable for monitoring HCV RNA loads, and is expected to have an important role in providing a predictive marker for early therapeutic outcomes. In discrepant cases in which no RVR is proved by either assay, it was assumed important to consider continuation of treatment and to attempt to achieve a sustained virological response.

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Multicenter prospective study to optimize the efficacy of triple therapy with telaprevir in patients with genotype 1b hepatitis C virus infection according to an algorithm based on the drug Adherence, IL‐28B Gene Allele and Viral Response Trial (AG & RGT)

Abstract: Triple therapy yielded a high SVR rate in the AG & RGT trial via attenuation of viral relapse by prolonged ribavirin/PEG IFN-α-2b administration. © 2015 The Japan Society of Hepatology.

Cited by 4 publications

References 18 publications

The CUPIC algorithm: an accurate model for the prediction of sustained viral response under telaprevir or boceprevir triple therapy in cirrhotic patients

The CUPIC algorithm: an accurate model for the prediction of sustained viral response under telaprevir or boceprevir triple therapy in cirrhotic patients

Significance of variants associated with resistance to NS5A inhibitors in Japanese patients with genotype 1b hepatitis C virus infection as evaluated using cycling-probe real-time PCR combined with direct sequencing

Clinical efficacy of the highly sensitive hepatitis C virus RNA quantitative assay in patients with relapse following interferon-based therapy with second-generation direct-acting antivirals

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