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. 2016 Oct;33(10):1797-1813. doi: 10.1007/s12325-016-0396-4. Epub 2016 Aug 12.

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.

Keywords: Access to treatment; Genotype 4; HCV; Hepatology; Infectious diseases; Peginterferon alfa; Predictors; Ribavirin; Sustained virologic response.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Observational Study

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use
  • Drug Therapy, Combination
  • Ethnicity
  • Female
  • Hepacivirus* / drug effects
  • Hepacivirus* / genetics
  • Hepatitis C, Chronic* / diagnosis
  • Hepatitis C, Chronic* / drug therapy
  • Hepatitis C, Chronic* / ethnology
  • Hepatitis C, Chronic* / virology
  • Humans
  • Interferon-alpha / therapeutic use*
  • International Cooperation
  • Male
  • Models, Theoretical
  • Outcome Assessment, Health Care
  • Polyethylene Glycols / therapeutic use*
  • Predictive Value of Tests
  • Recombinant Proteins / therapeutic use
  • Research Design
  • Ribavirin / therapeutic use*
  • Sustained Virologic Response

Substances

  • Antiviral Agents
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a