Evidence map›Paper›PMID 24982076›Full record

Trial reportAntimicrobial agents and chemotherapy2014

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.

Cédric Laouénan, Patrick Marcellin, Martine Lapalus, Feryel Khelifa-Mouri, Nathalie Boyer, Fabien Zoulim, Lawrence Serfaty, Jean-Pierre Bronowicki, Michelle Martinot-Peignoux, Olivier Lada and 8 more

Open access · bronzeAbstract readClinical TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.1field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Trial
  2. Modelling hepatitis C therapy--predicting effects of treatment.Nature reviews. Gastroenterology & hepatology · 2015
    Review
  3. HCV Kinetic Models and Their Implications in Drug Development.CPT: pharmacometrics & systems pharmacology · 2015
    Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 4 institutions in 1 country.

Cédric LaouénanINSERM, IAME, UMR 1137, University Paris Diderot, Sorbonne Paris Cité, Paris, France AP-HP, Hôpital Bichat, Department of Biostatistics, Paris, France cedric.laouenan@inserm.fr.
Patrick MarcellinINSERM, CRI Paris Montmartre, UMR 1149, University Paris Diderot, Clichy, France AP-HP, Hôpital Beaujon, Hepatology, Physiopathology and Treatment of Viral Hepatitis, Clichy, France.
Martine LapalusINSERM, CRI Paris Montmartre, UMR 1149, University Paris Diderot, Clichy, France.
Feryel Khelifa-MouriAP-HP, Hôpital Beaujon, Hepatology, Physiopathology and Treatment of Viral Hepatitis, Clichy, France.
Nathalie BoyerAP-HP, Hôpital Beaujon, Hepatology, Physiopathology and Treatment of Viral Hepatitis, Clichy, France.
Fabien ZoulimINSERM, UMR 1052, University of Lyon, Lyon, France Hospices Civils de Lyon, Department of Hepatology, Lyon, France.
Lawrence SerfatyAP-HP, Hôpital Saint-Antoine, Department of Hepatology, Paris, France.
Jean-Pierre BronowickiINSERM, UMR 954, University of Lorraine, Vandoeuvre-les-Nancy, France Centre Hospitalier Universitaire de Nancy, Department of Hepatology, Vandoeuvre-les-Nancy, France.
Michelle Martinot-PeignouxINSERM, CRI Paris Montmartre, UMR 1149, University Paris Diderot, Clichy, France.
Olivier LadaINSERM, CRI Paris Montmartre, UMR 1149, University Paris Diderot, Clichy, France.
Tarik AsselahINSERM, CRI Paris Montmartre, UMR 1149, University Paris Diderot, Clichy, France AP-HP, Hôpital Beaujon, Hepatology, Physiopathology and Treatment of Viral Hepatitis, Clichy, France.
Céline DorivalINSERM, UMR 707, University Pierre et Marie Curie, Paris, France.
Christophe HézodeINSERM, UMR 955, University Paris-Est, Créteil, France AP-HP, Hôpital Henri Mondor, Department of Hepatology, Créteil, France.
Fabrice CarratINSERM, UMR 707, University Pierre et Marie Curie, Paris, France AP-HP, Hôpital Saint-Antoine, Department of Public Health, Paris, France.
Florence NicotCHU Toulouse, IFB Purpan, Virology Laboratory, Toulouse, France.
Gilles PeytavinINSERM, IAME, UMR 1137, University Paris Diderot, Sorbonne Paris Cité, Paris, France AP-HP, Hôpital Bichat, Department of Clinical Pharmacokinetics, Paris, France.
France MentréINSERM, IAME, UMR 1137, University Paris Diderot, Sorbonne Paris Cité, Paris, France AP-HP, Hôpital Bichat, Department of Biostatistics, Paris, France.
Jeremie GuedjINSERM, IAME, UMR 1137, University Paris Diderot, Sorbonne Paris Cité, Paris, France.
Inserm · FRHôpital Beaujon · FRSorbonne Université · FRUniversité Claude Bernard Lyon 1 · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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 (EC50) (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.

Indexed as

AdultAntiviral AgentsDrug Therapy, CombinationFemaleHepacivirusHepatitis CHumansInterferon-alphaKineticsMaleMiddle AgedModels, BiologicalOligopeptidesPolyethylene GlycolsProlineRecombinant ProteinsAntiviral AgentsInterferon-alphaN-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamideOligopeptidespeginterferon alfa-2aPolyethylene GlycolsProlineRecombinant Proteinstelaprevir

Identifiers

PMID24982076
PMCPMC4135822
OpenAlexW2012900888

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.