Ribavirin dose management in HCV patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin

Liver Int. 2018 Sep;38(9):1571-1575. doi: 10.1111/liv.13708. Epub 2018 Mar 14.

Abstract

Background & aims: Some individuals with hepatitis C virus infection treated with direct-acting antivirals require ribavirin to maximize sustained virological response rates. We describe the clinical management of ribavirin dosing in hepatitis C virus-infected patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin.

Methods: We performed a post hoc analysis of patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin for 12 or 24 weeks in six phase 3 trials. Multivariate stepwise logistic regression models assessed predictors associated with ribavirin dose adjustments and with developing anaemia.

Results: Of 1548 patients, 100 (6.5%) modified ribavirin dose due to haemoglobin declines, of which 99% achieved sustained virological response at 12 weeks post-treatment. Median time to first ribavirin dose reduction was 37 days. Low baseline haemoglobin was significantly associated with an increased risk of requiring ribavirin dose modification (odds ratio: 0.618 [0.518, 0.738]; P < .001) and developing anaemia (odds ratio: 0.379 [0.243, 0.593]; P < .001).

Conclusions: Ribavirin dose reductions were infrequent, occurred early in treatment, and did not impact sustained virological response at 12 weeks post-treatment. Patients with low baseline haemoglobin should be monitored for on-treatment anaemia.

Trial registration: ClinicalTrials.gov NCT01716585 NCT01715415 NCT01674725 NCT01767116 NCT01833533 NCT01704755.

Keywords: anaemia; dasabuvir; ombitasvir; paritaprevir; ribavirin.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Naphthylamine
  • Adult
  • Anilides / therapeutic use
  • Antiviral Agents / administration & dosage*
  • Carbamates / therapeutic use
  • Cyclopropanes
  • Drug Therapy, Combination
  • Female
  • Hepacivirus / genetics
  • Hepatitis C / drug therapy*
  • Humans
  • Internationality
  • Lactams, Macrocyclic
  • Logistic Models
  • Macrocyclic Compounds / therapeutic use
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Proline / analogs & derivatives
  • Ribavirin / administration & dosage*
  • Ritonavir / therapeutic use
  • Sulfonamides / therapeutic use
  • Sustained Virologic Response
  • Treatment Outcome
  • Uracil / analogs & derivatives
  • Uracil / therapeutic use
  • Valine

Substances

  • Anilides
  • Antiviral Agents
  • Carbamates
  • Cyclopropanes
  • Lactams, Macrocyclic
  • Macrocyclic Compounds
  • Sulfonamides
  • ombitasvir
  • Ribavirin
  • Uracil
  • Proline
  • 2-Naphthylamine
  • dasabuvir
  • Valine
  • Ritonavir
  • paritaprevir

Associated data

  • ClinicalTrials.gov/NCT01716585
  • ClinicalTrials.gov/NCT01715415
  • ClinicalTrials.gov/NCT01674725
  • ClinicalTrials.gov/NCT01767116
  • ClinicalTrials.gov/NCT01833533
  • ClinicalTrials.gov/NCT01704755