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Efficacy and Safety of Modeling-Based Response Guided Therapy with Direct Acting Anti-Viral Agents for Treatment Optimization in Chronic Hepatitis C Infection- A Pilot Study

57 Pages Posted: 28 Jan 2020

See all articles by Ohad Etzion

Ohad Etzion

Soroka University Medical Center - Department of Gastroenterology and Liver Diseases

Harel Dahari

Loyola University of Chicago

David Yardeni

Soroka University Medical Center - Department of Gastroenterology and Liver Diseases

Assaf Issachar

Tel Aviv University - Rabin Medical Center

Anat Nevo-Shor

Soroka University Medical Center - Department of Gastroenterology and Liver Diseases

Michal Cohen-Naftaly

Tel Aviv University - Rabin Medical Center

Yafa Ashur

Soroka University Medical Center

Susan L. Uprichard

Loyola University of Chicago

Orly Sneh Arbib

Tel Aviv University - Rabin Medical Center

Daniela Munteanu

Soroka University Medical Center - Department of Gastroenterology and Liver Diseases

Marius Braun

Tel Aviv University - Rabin Medical Center

Scott J. Cotler

Loyola University of Chicago

Naim Abufreha

Soroka University Medical Center - Department of Gastroenterology and Liver Diseases

Ayelet Keren-Naos

Soroka University Medical Center

Yonat Shemer-Avni

Soroka University Medical Center

Orna Mor

Chaim Sheba Medical Center

Jayanah Murad

Soroka University Medical Center

Victor Novack

Soroka University Medical Center

Amir Shlomai

Tel Aviv University - Rabin Medical Center

More...

Abstract

Background: The advent of direct-acting antivirals (DAAs) has transformed the landscape of hepatitis C virus (HCV) management. However, the high cost of DAAs therapy has become a major barrier to HCV elimination. We aimed to prospectively evaluate the efficacy and safety of reducing the duration of DAAs therapy using response-guided therapy approach based on mathematical modeling of viral kinetics.

Methods: Patients were treated with DAAs according to the physicians’ preference. HCV was measured at baseline and at day 2 and weeks 1, 2 and 4 after treatment initiation. The primary endpoint was the proportion of patients with sustained-virological response (SVR) at 12 and/or 24 weeks post-treatment.

Findings: Twenty-nine patients (mean age 54±16, 44% females, 73% with HCV genotype 1), were enrolled and all completed therapy. Sofosbuvir/velpatasvir, elbasvir/grazoprevir, sofosbuvir/ledipasvir and glecaprevir/pibrentasvir, were administered in 38%, 27%, 21% and 14% of patients, respectively. Treatment duration was shortened in 11 of the 29 patients (38%). SVR was achieved in 28 of the 29 patients (97%). Relapse occurred post treatment in a single case of a non-cirrhotic male with genotype 3, who was treated with sofosbuvir/velpatasvir for 6 weeks. Virus sequencing did not identify baseline or treatment emergent resistance associated substitutions.

Interpretation: Real-time modeling can be utilized for shortening DAAs duration in approximately 40% of patients without compromising treatment efficacy. Implementation of this model on a wider scale may lead to significant cost-saving and to improved access to anti-HCV care.

Trial Registration: ClinicalTrials.gov Identifier: NCT03603327.

Funding Statement: This research was supported in part by Clalit Health Services and the National Institutes of Health (NIH) and extramural NIH grants R01-AI078881 and R01GM121600.

Declaration of Interests: OE has consulted for Gilead and Abbvie and received lecture fees from Gilead, Abbvie and MSD. HD has consulted for CoCrystal Inc. None of the other authors has any financial interest or conflict of interest related to this research.

Ethics Approval Statement: The study was approved by the institutional review boards of Soroka and Rabin Medical Centers and was conducted in compliance with the Declaration of Helsinki, Good Clinical Practice guidelines, and local regulatory requirements. All patients provided written informed consent.

Keywords: Hepatitis C virus; Direct-acting anti viral agents; Response-guided therapy; Mathematical modeling; Viral kinetics

Suggested Citation

Etzion, Ohad and Dahari, Harel and Yardeni, David and Issachar, Assaf and Nevo-Shor, Anat and Cohen-Naftaly, Michal and Ashur, Yafa and Uprichard, Susan L. and Sneh Arbib, Orly and Munteanu, Daniela and Braun, Marius and Cotler, Scott J. and Abufreha, Naim and Keren-Naos, Ayelet and Shemer-Avni, Yonat and Mor, Orna and Murad, Jayanah and Novack, Victor and Shlomai, Amir, Efficacy and Safety of Modeling-Based Response Guided Therapy with Direct Acting Anti-Viral Agents for Treatment Optimization in Chronic Hepatitis C Infection- A Pilot Study (January 6, 2020). Available at SSRN: https://ssrn.com/abstract=3514742 or http://dx.doi.org/10.2139/ssrn.3514742

Ohad Etzion (Contact Author)

Soroka University Medical Center - Department of Gastroenterology and Liver Diseases ( email )

151 Rager Yitzhak Blvd
Beer-Sheva, 84171
Israel

Harel Dahari

Loyola University of Chicago

25 East Pearson Street
Chicago, IL 60611
United States

David Yardeni

Soroka University Medical Center - Department of Gastroenterology and Liver Diseases

151 Rager Yitzhak Blvd
Beer-Sheva, 84171
Israel

Assaf Issachar

Tel Aviv University - Rabin Medical Center

Tikva
Israel

Anat Nevo-Shor

Soroka University Medical Center - Department of Gastroenterology and Liver Diseases

151 Rager Yitzhak Blvd
Beer-Sheva, 84171
Israel

Michal Cohen-Naftaly

Tel Aviv University - Rabin Medical Center

Tikva
Israel

Yafa Ashur

Soroka University Medical Center

POB 151
First floor, Administration Building, Room 12
Beer Sheva
Israel

Susan L. Uprichard

Loyola University of Chicago

25 East Pearson Street
Chicago, IL 60611
United States

Orly Sneh Arbib

Tel Aviv University - Rabin Medical Center

Tikva
Israel

Daniela Munteanu

Soroka University Medical Center - Department of Gastroenterology and Liver Diseases

151 Rager Yitzhak Blvd
Beer-Sheva, 84171
Israel

Marius Braun

Tel Aviv University - Rabin Medical Center

Tikva
Israel

Scott J. Cotler

Loyola University of Chicago

25 East Pearson Street
Chicago, IL 60611
United States

Naim Abufreha

Soroka University Medical Center - Department of Gastroenterology and Liver Diseases

151 Rager Yitzhak Blvd
Beer-Sheva, 84171
Israel

Ayelet Keren-Naos

Soroka University Medical Center

POB 151
First floor, Administration Building, Room 12
Beer Sheva
Israel

Yonat Shemer-Avni

Soroka University Medical Center

POB 151
First floor, Administration Building, Room 12
Beer Sheva
Israel

Orna Mor

Chaim Sheba Medical Center

Tel Hashomer
Ramat-Gan
Israel

Jayanah Murad

Soroka University Medical Center

POB 151
First floor, Administration Building, Room 12
Beer Sheva
Israel

Victor Novack

Soroka University Medical Center

POB 151
First floor, Administration Building, Room 12
Beer Sheva
Israel

Amir Shlomai

Tel Aviv University - Rabin Medical Center

Tikva
Israel

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