Detection of low HCV viraemia by repeated HCV RNA testing predicts treatment failure to triple therapy with telaprevir

Maasoumy, Benjamin; Cobb, Bryan; Bremer, Birgit; Luk, Kevin; Halfon, Philippe; Aslam, Shagufta; Manns, Michael P.; Cornberg, Markus; Wedemeyer, Heiner

doi:10.1111/apt.12544

Cited by 30 publications

(30 citation statements)

References 13 publications

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“…This discrepancy in eligibility for shorter treatment is explained by the probabilities of detection of HCV RNA at the LOD of HCV RNA assays. In another study, Maasoumy et al showed that rates of detectable and undetectable HCV RNA at week 4 of triple therapy showed considerable variation of approximately 30% just by measuring the same samples several times using different versions of the Roche Cobas AmpliPrep/Cobas HCV test and HPS assay (24). Braun et al also demonstrated different rates of detectability by replicate testing of WHO standards at low viral loads using HPS or ART (25).…”

Section: Discussionmentioning

confidence: 99%

An OPTIMIZE Study Retrospective Analysis for Management of Telaprevir-Treated Hepatitis C Virus (HCV)-Infected Patients by Use of the Abbott RealTi m e HCV RNA Assay

et al. 2015

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e Protease inhibitor (PI)-based response-guided triple therapies for hepatitis C virus (HCV) infection are still widely used. Noncirrhotic treatment-naive and prior relapser patients receiving telaprevir-based treatment are eligible for shorter, 24-week total therapy if HCV RNA is undetectable at both weeks 4 and 12. In this study, the concordance in HCV RNA assessments between the Roche High Pure System/Cobas TaqMan and Abbott RealTime HCV RNA assays and the impacts of different HCV RNA cutoffs on treatment outcome were evaluated. A total of 2,629 samples from 663 HCV genotype 1 patients receiving telaprevir/pegylated interferon/ribavirin in OPTIMIZE were analyzed using the High Pure System and reanalyzed using Abbott RealTime (limits of detection, 15.1 IU/ml versus 8.3 IU/ml; limits of quantification, 25 IU/ml versus 12 IU/ml, respectively). Overall, good concordance was observed between the assays. Using undetectable HCV RNA at week 4, 34% of the patients would be eligible for shorter treatment duration with Abbott RealTime versus 72% with the High Pure System. However, using <12 IU/ml for Abbott RealTime, a similar proportion (74%) would be eligible. Of the patients receiving 24-week total therapy, 87% achieved a sustained virologic response with undetectable HCV RNA by the High Pure System or <12 IU/ml by Abbott RealTime; however, 92% of the patients with undetectable HCV RNA by Abbott RealTime achieved a sustained virologic response. Using undetectable HCV RNA as the cutoff, the more sensitive Abbott RealTime assay would identify fewer patients eligible for shorter treatment than the High Pure System. Our data confirm the <12-IU/ml cutoff, as previously established in other studies of the Abbott RealTime assay, to determine eligibility for shortened PI-based HCV treatment. (The study was registered with ClinicalTrials.gov under registration no. NCT01241760.)

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Section: Discussionmentioning

confidence: 99%

An OPTIMIZE Study Retrospective Analysis for Management of Telaprevir-Treated Hepatitis C Virus (HCV)-Infected Patients by Use of the Abbott RealTi m e HCV RNA Assay

et al. 2015

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“…We thank Heron and colleagues for their interest in our report 1,2 and agree that the cost-effectiveness of this therapy is called into question by the number of patients who are unable to complete treatment and successfully achieve sustained virological response. We are analysing the cost-effectiveness of this regimen using real-world data.…”

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confidence: 86%

Commentary: detection of low level viraemia in telaprevir‐based triple therapy for hepatitis C virus

Elsharkawy

2014

Aliment Pharmacol Ther

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1, 2 and agree that the cost-effectiveness of this therapy is called into question by the number of patients who are unable to complete treatment and successfully achieve sustained virological response. We are analysing the cost-effectiveness of this regimen using real-world data.Ribavirin dose reduction during treatment was not recorded in more than 50% of our patients. As decisions on adverse event management were at the discretion of individual clinicians, anaemia management varied. Several patients received erythropoietin (EPO) therapy prior to ribavirin dose reduction, and some had signs of severe anaemia at the first or second visit and required blood transfusion before dose reduction might have been possible. Thus, great importance must be placed on careful patient monitoring when using these medications. With some exceptions, ribavirin dose was reduced when patients had haemoglobin levels of 10 g/dL or less. If haemoglobin levels fell to below 8.5 g/dL, patients were given EPO.As mentioned in our report, only 16% of our patients had IL28b testing; the results of this test were not used to reach a decision on initiation of therapy. We did not collect hepatitis C virus genotype-1 subtype data, but future studies will certainly examine the effect that genotype and subtype may have on the occurrence of adverse events. ACKNOWLEDGEMENTThe authors' declarations of personal and financial interests are unchanged from those in the original article.

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“…Similarly, in one study that assessed on-treatment HCV RNA of patients undergoing telaprevir-based triple therapy, samples were tested in triplicate by the first and second version of CAP/CTM and with HPS/CTM. In samples that had undetectable HCV RNA according to one assay, retesting with the respective other assays resulted in detectable HCV RNA in 32-50% of cases [44].…”

Section: Lower Limit Of Quantification and Limit Of Detectionmentioning

confidence: 99%

“…Thus, eligibility for shortened therapy should be based on attainment of undetectable HCV RNA at week 4 only, whereas patients with detectable/not quantifiable (<25 IU/ml) HCV RNA should receive a full course of therapy [43]. However, the HPS/CTM assay that was used in these trials has been shown to be less sensitive compared to CAP/CTM and ART, which are mostly used in clinical routine [39,44,57]. Indeed, some data suggest that assay-specific RGT criteria may be required given the significant performance differences among HCV RNA assays.…”

Section: The Role Of Hcv Rna Quantification During Protease Inhibitormentioning

confidence: 99%

Diagnostics in hepatitis C: The end of response-guided therapy?

Maasoumy

Vermehren

2016

Journal of Hepatology

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On-treatment hepatitis C virus (HCV) RNA has been used to predict response to interferon (IFN)-based therapy. The concept of response-guided treatment (RGT) was established to determine optimal treatment duration and to early identify patients not responding to futile therapies. RGT helped to improve sustained virologic response (SVR) rates and lower the rates of adverse effects. RGT was of particular importance for telaprevir- and boceprevir-based triple therapies. RGT strategies are dependent on highly sensitive and reproducible HCV RNA quantification. However, different HCV RNA assays are used in routine clinical practice and these differ significantly in their performance characteristics. The development of IFN-free therapies has fundamentally changed the role of on-treatment HCV RNA for SVR prediction. Given the high efficacy and excellent tolerability of IFN-free regimens, the interest in treatment individualization has decreased. However, shorter treatment durations may still be desirable, particularly with respect to the high costs of current IFN-free direct-acting antiviral agents (DAAs). Moreover, some difficult-to-treat patients remain, e.g., those infected with HCV genotype 3 in whom the current standard of care may not always be sufficient to achieve SVR, especially in treatment-experienced patients with cirrhosis. Here, a RGT extension may be feasible. However, current data on the predictive value of on-treatment HCV RNA are limited and have shown conflicting results. As more potent DAAs become available, the role of response prediction may diminish further. Currently, shorter treatment duration is only based on baseline HCV RNA whereas no RGT strategy is recommended for any of the approved DAA regimens available.

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Detection of low HCV viraemia by repeated HCV RNA testing predicts treatment failure to triple therapy with telaprevir

Cited by 30 publications

References 13 publications

An OPTIMIZE Study Retrospective Analysis for Management of Telaprevir-Treated Hepatitis C Virus (HCV)-Infected Patients by Use of the Abbott RealTi m e HCV RNA Assay

An OPTIMIZE Study Retrospective Analysis for Management of Telaprevir-Treated Hepatitis C Virus (HCV)-Infected Patients by Use of the Abbott RealTi m e HCV RNA Assay

Commentary: detection of low level viraemia in telaprevir‐based triple therapy for hepatitis C virus

Diagnostics in hepatitis C: The end of response-guided therapy?

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