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Simple Predictive Model for Identifying Patients with Chronic Hepatitis C and Hepatitis C Virus Genotype 4 Infection with a High Probability of Sustained Virologic Response with Peginterferon Alfa-2a/Ribavirin: Pooled Analysis of Data from Two Large, International Cohort Studies

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Abstract

Introduction

Wherever access to direct-acting antiviral agents is restricted, dual peginterferon/ribavirin (PegIFN/RBV) therapy remains an option for treatment of hepatitis C virus (HCV) genotype 4 (GT4) infection, which predominates in the Middle East and Sub-Saharan Africa. Our goal was to develop a baseline scoring system to identify GT4-infected patients with a low or high probability of achieving a sustained virologic response (SVR) with PegIFN alfa-2a/RBV using data from two large cohort studies.

Methods

Associations between baseline characteristics and SVR were explored by generalized additive models and multiple logistic regression analysis to develop a predictive model, which was then checked by bootstrapping. The score comprised four factors with points assigned thus: age ≤40, 3 points; >40 but ≤55, 2 points; alanine aminotransferase ≤1 or >3× the upper limit of normal, 1 point; no cirrhosis, 1 point; HCV RNA <50,000 IU/mL, 2 points; 50,000 to <400,000 IU/mL, 1 point. The values for a given patient are summed to produce a score from 0 to 7 where higher scores indicate higher chances of SVR.

Results

Among the 459 patients, 28 (6%), 50 (11%), 92 (20%), 121 (26%), 103 (22%), and 65 (14%) patients had scores of 0–1, 2, 3, 4, 5, and 6–7, respectively, with respective SVR rates of 11%, 28%, 50%, 57%, 63%, and 83%. Relapse rates decreased with increasing prediction score (80%, 39%, 15%, 19%, 5%, and 7%, respectively). SVR rates were consistently higher in Caucasian than Black patients and in patients with a rapid virologic response HCV RNA <50 IU/mL at week 4); however, the trend toward higher SVR rates with increasing score remained apparent in each subgroup.

Conclusion

In conclusion, a simple scoring system can be used to identify GT4-infected patients with a high probability of achieving an SVR with PegIFN alfa-2a/RBV.

Funding

F. Hoffmann-La Roche Ltd.

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Acknowledgments

Sponsorship of these studies and article processing charges were funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. Editorial assistance in the preparation of this manuscript was provided by Dr. Manda Gent and Blair Jarvis of Health Interactions. Support for this assistance was funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.

Disclosures

Tarik Asselah is a speaker/consultant for Roche, AbbVie, Achillion, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck. Gamal Esmat is a speaker, investigator and/or advisory board member for AbbVie, Bristol-Myers Squibb, Janssen, Merck, F Hoffmann-La Roche. Faisal M. Sanai is a consultant for/advises, is on the speakers’ bureau of, and has received grant support from F. Hoffmann-La Roche, and Bristol-Myers Squibb. He has been a consultant for, and advised Merck, Gilead Sciences, Janssen Pharmaceuticals and AbbVie. He is on the speakers’ bureau of Merck, Gilead Sciences, and AbbVie. Ioannis Goulis is a speaker, investigator and/or advisory board member for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, F Hoffmann-La Roche. Diethelm Messinger is an employee of PROMETRIS GmbH. PROMETRIS GmbH has a contract with F. Hoffmann-La Roche Ltd to provide statistical support. Georgios Bakalos is an employee of F. Hoffmann-La Roche Ltd. Imam Waked is a speaker, investigator and/or advisory board member for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, Pharco, F Hoffmann-La Roche.

Compliance with Ethics Guidelines

All procedures followed in the original studies were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964. Informed consent was obtained from all patients for being included in the study.

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Authors and Affiliations

  1. Centre de Recherche sur l’Inflammation (CRI), INSERM UMR 1149, Service d’Hépatologie, Université Paris Diderot, AP-HP Hôpital Beaujon, Clichy, 100 Bd du Général Leclerc, 92110, Clichy, France

    Tarik Asselah

  2. Endemic Medicine Department, Cairo University, Cairo, Egypt

    Gamal Esmat

  3. Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia

    Faisal M. Sanai

  4. Gastroenterology Unit, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia

    Faisal M. Sanai

  5. 4th Department of Internal Medicine, Hippokration General Hospital, Αristotle University of Thessaloniki Medical School, Thessaloniki, Greece

    Ioannis Goulis

  6. PROMETRIS GmbH, Mannheim, Germany

    Diethelm Messinger

  7. F. Hoffmann-La Roche Ltd, Basel, Switzerland

    Georgios Bakalos

  8. National Liver Institute, Shebeen El Kom, Egypt

    Imam Waked

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  1. Tarik Asselah
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  2. Gamal Esmat
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Correspondence to Tarik Asselah.

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Asselah, T., Esmat, G., Sanai, F.M. et al. Simple Predictive Model for Identifying Patients with Chronic Hepatitis C and Hepatitis C Virus Genotype 4 Infection with a High Probability of Sustained Virologic Response with Peginterferon Alfa-2a/Ribavirin: Pooled Analysis of Data from Two Large, International Cohort Studies. Adv Ther 33, 1797–1813 (2016). https://doi.org/10.1007/s12325-016-0396-4

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