Eltrombopag dose predictors in thrombocytopenic subjects with hepatitis C virus infection

Clin Exp Pharmacol Physiol. 2015 Oct;42(10):1030-5. doi: 10.1111/1440-1681.12451.

Abstract

This study aims to identify patient characteristics that predict effective eltrombopag dosage for the treatment of Hepatitis C virus (HCV)-related thrombocytopenia. Demographic, clinical and genetic data collected from thrombocytopenic patients (n = 1463, age ≥ 18 years) with chronic HCV infection who were able to achieve a target platelet count of > 90 × 10(9) /L following eltrombopag treatment. Patients were categorized into four groups (25, 50, 75, and 100 mg) based on the eltrombopag dose needed to achieve the target platelet count. Eltrombopag dose predictors were identified using a two stage approach. First, bivariate analysis, using anova for continuous variables and Chi-square test for categorical variables, was performed to identify possible predictors of eltrombopag dose (P < 0.05). Second, ordinal logistic regression with stepwise addition followed by backward deletion was then performed using predictors identified in bivariate analysis step to produce final model containing independent predictors at P < 0.05. Ordinal logistic model identified several predictors of eltrombopag dose. Predictors of higher eltrombopag dose include: having a HCV genotype 2 or 3, being Central/South Asian, being White (Caucasian or European heritage), increased weight, and increased spleen length. Predictors of lower eltrombopag dose include: female gender, increased age, having a higher ALP plasma concentration, increased creatinine clearance, increased baseline lymphocytes count, and increased baseline platelet count. In conclusion, this study identified patient characteristics that predict effective eltrombopag dose for the treatment of HCV-related thrombocytopenia. Early selection of the optimal eltrombopag dose expedites the initiation of antiviral therapy. This is expected to improve the antiviral therapy outcome before the patient progress into liver decompensation.

Trial registration: ClinicalTrials.gov NCT00516321 NCT00529568.

Keywords: eltrombopag dose; hepatitis C virus; predictors; thrombocytopenia.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / therapeutic use
  • Benzoates / pharmacology*
  • Benzoates / therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / drug therapy
  • Humans
  • Hydrazines / pharmacology*
  • Hydrazines / therapeutic use
  • Male
  • Middle Aged
  • Pyrazoles / pharmacology*
  • Pyrazoles / therapeutic use
  • Thrombocytopenia / complications*
  • Thrombocytopenia / drug therapy*
  • Treatment Outcome
  • Young Adult

Substances

  • Antiviral Agents
  • Benzoates
  • Hydrazines
  • Pyrazoles
  • eltrombopag

Associated data

  • ClinicalTrials.gov/NCT00516321
  • ClinicalTrials.gov/NCT00529568