The Relative Efficacy of Boceprevir and Telaprevir in the Treatment of Hepatitis C Virus Genotype 1

Kieran, Jennifer; Schmitz, Susanne; O’Leary, Aisling; Walsh, Cathal; Bergin, Colm; Norris, Suzanne; Barry, Michael

doi:10.1093/cid/cis880

Cited by 24 publications

(29 citation statements)

References 26 publications

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“…Because the loss rate of infected cells is strongly related to the treatment duration needed to achieve SVR (15), our results suggest that the time to achieve SVR in this population could be longer than what had been predicted from clinical trials (15). Consistent with this prediction, the relapse rate in the ANRS CO20-CUPIC trial was 41% in both treatment groups (13), i.e., much higher than that reported in treatment-experienced patients in phase 3 clinical trials (12% to 27%) (9,11,22).…”

Section: Discussionsupporting

confidence: 72%

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Using Pharmacokinetic and Viral Kinetic Modeling To Estimate the Antiviral Effectiveness of Telaprevir, Boceprevir, and Pegylated Interferon during Triple Therapy in Treatment-Experienced Hepatitis C Virus-Infected Cirrhotic Patients

Laouénan

Marcellin

Lapalus

et al. 2014

Antimicrob Agents Chemother

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Triple therapy combining a protease inhibitor (PI) (telaprevir or boceprevir), pegylated interferon (PEG-IFN), and ribavirin (RBV) has dramatically increased the chance of eradicating hepatitis C virus (HCV). However, the efficacy of this treatment remains suboptimal in cirrhotic treatment-experienced patients. Here, we aimed to better understand the origin of this impaired response by estimating the antiviral effectiveness of each drug. Fifteen HCV genotype 1-infected patients with compensated cirrhosis, who were nonresponders to prior PEG-IFN/RBV therapy, were enrolled in a nonrandomized study. HCV RNA and concentrations of PIs, PEG-IFN, and RBV were frequently assessed in the first 12 weeks of treatment and were analyzed using a pharmacokinetic/viral kinetic model. The two PIs achieved similar levels of molar concentrations (P ‫؍‬ 0.5), but there was a significant difference in the 50% effective concentrations (EC 50 ) (P ‫؍‬ 0.008), leading to greater effectiveness for telaprevir than for boceprevir in blocking viral production (99.8% versus 99.0%, respectively, P ‫؍‬ 0.002). In all patients, the antiviral effectiveness of PEG-IFN was modest (43.4%), and there was no significant contribution of RBV exposure to the total antiviral effectiveness. The second phase of viral decline, which is attributed to the loss rate of infected cells, was slow (0.19 day ؊1 ) and was higher in patients who subsequently eradicated HCV (P ‫؍‬ 0.03). The two PIs achieved high levels of antiviral effectiveness. However, the suboptimal antiviral effectiveness of PEG-IFN/RBV and the low loss of infected cells suggest that a longer treatment duration might be needed in cirrhotic treatment-experienced patients and that a future IFN-free regimen may be particularly beneficial in these patients.

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Section: Discussionsupporting

confidence: 72%

“…For both PI drugs, no significant increases in trough concentrations over time were observed, consistent with the fact that they have short elimination half-lives (22). Therefore, concentrations for both telaprevir and boceprevir were fitted using a constant model, where C ss is the trough concentration:…”

Section: Methodsmentioning

confidence: 79%

Using Pharmacokinetic and Viral Kinetic Modeling To Estimate the Antiviral Effectiveness of Telaprevir, Boceprevir, and Pegylated Interferon during Triple Therapy in Treatment-Experienced Hepatitis C Virus-Infected Cirrhotic Patients

Laouénan

Marcellin

Lapalus

et al. 2014

Antimicrob Agents Chemother

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“…To check validity of pooling, we compared baseline characteristics and treatment outcomes between telaprevir and boceprevir patients. [14]…”

Section: Methodsmentioning

confidence: 99%

Limited Generalizability of Registration Trials in Hepatitis C: A Nationwide Cohort Study

et al. 2016

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BackgroundApproval of drugs in chronic hepatitis C is supported by registration trials. These trials might have limited generalizability through use of strict eligibility criteria. We compared effectiveness and safety of real world hepatitis C patients eligible and ineligible for registration trials.MethodsWe performed a nationwide, multicenter, retrospective cohort study of chronic hepatitis C patients treated in the real world. We applied a combined set of inclusion and exclusion criteria of registration trials to our cohort to determine eligibility. We compared effectiveness and safety in eligible vs. ineligible patients, and performed sensitivity analyses with strict criteria. Further, we used log binomial regression to assess relative risks of criteria on outcomes.ResultsIn this cohort (n = 467) 47% of patients would have been ineligible for registration trials. Main exclusion criteria were related to hepatic decompensation and co-morbidity (cardiac disease, anemia, malignancy and neutropenia), and were associated with an increased risk for serious adverse events (RR 1.45–2.31). Ineligible patients developed significantly more serious adverse events than eligible patients (27% vs. 11%, p< 0.001). Effectiveness was decreased if strict criteria were used.ConclusionsNearly half of real world hepatitis C patients would have been excluded from registration trials, and these patients are at increased risk to develop serious adverse events. Hepatic decompensation and co-morbidity were important exclusion criteria, and were related to toxicity. Therefore, new drugs should also be studied in these patients, to genuinely assess benefits and risk of therapy in the real world population.

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“…There were SR and MA reviews comparing the benefits and harms of pegylated interferon plus ribavirin and interferon plus ribavirin,16 the safety and effects of pegylated interferon α-2a or α-2b plus ribavirin,17,18 the efficacy of adding statins to interferon α plus ribavirin,19 the relative efficacy among boceprevir and telaprevir,20 comparison of the efficacy and safety of telaprevir,21 the comparative effectiveness of antiviral treatment,22 antiviral therapy (interferon-α plus cyclosporine A and tacrolimus) for recurrent HCV after liver transplantation,23 and interferon for interferon-nonresponding and relapsing patients with chronic HCV 24. Moreover, there were studies on the effects of nitazoxanide (a synthetic nitrothiazolyl-salicylamide derivative and an antiprotozoal agent),25 and the association between 25-hydroxyvitamin D and a sustained virological response (SVR) 26…”

Section: Hcvmentioning

confidence: 99%

Overview and recent trends of systematic reviews and meta-analyses in hepatology

Kim

Baik

2014

Clin Mol Hepatol

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A systematic review (SR) is a research methodology that involves a comprehensive search for and analysis of relevant studies on a specific topic. A strict and objective research process is conducted that comprises a systematic and comprehensive literature search in accordance with predetermined inclusion/exclusion criteria, and an assessment of the risk of bias of the selected literature. SRs require a multidisciplinary approach that necessitates cooperation with clinical experts, methodologists, other experts, and statisticians. A meta-analysis (MA) is a statistical method of quantitatively synthesizing data, where possible, from the primary literature selected for the SR. Review articles differ from SRs in that they lack a systematic methodology such as a literature search, selection of studies according to strict criteria, assessment of risk bias, and synthesis of the study results. The importance of evidence-based medicine (EBM) in the decision-making for public policy has recently been increasing thanks to the realization that it should be based on scientific research data. SRs and MAs are essential for EBM strategy and evidence-based clinical practice guidelines. This review addresses the current trends in SRs and MAs in the field of hepatology via a search of recently published articles in the Cochrane Library and Ovid-MEDLINE.

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The Relative Efficacy of Boceprevir and Telaprevir in the Treatment of Hepatitis C Virus Genotype 1

Cited by 24 publications

References 26 publications

Using Pharmacokinetic and Viral Kinetic Modeling To Estimate the Antiviral Effectiveness of Telaprevir, Boceprevir, and Pegylated Interferon during Triple Therapy in Treatment-Experienced Hepatitis C Virus-Infected Cirrhotic Patients

Using Pharmacokinetic and Viral Kinetic Modeling To Estimate the Antiviral Effectiveness of Telaprevir, Boceprevir, and Pegylated Interferon during Triple Therapy in Treatment-Experienced Hepatitis C Virus-Infected Cirrhotic Patients

Limited Generalizability of Registration Trials in Hepatitis C: A Nationwide Cohort Study

Overview and recent trends of systematic reviews and meta-analyses in hepatology

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