Patient-reported symptoms during and after direct-acting antiviral therapies for chronic hepatitis C: The PROP UP study

J Hepatol. 2019 Sep;71(3):486-497. doi: 10.1016/j.jhep.2019.04.016. Epub 2019 May 13.

Abstract

Background & aims: A comprehensive analysis of changes in symptoms and functioning during and after direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection has not been conducted for patients treated in real-world clinical settings. Therefore, we evaluated patient-reported outcomes (PROs) in a diverse cohort of patients with HCV treated with commonly prescribed DAAs.

Methods: PROP UP is a US multicenter observational study of 1,601 patients with HCV treated with DAAs in 2016-2017. PRO data were collected at baseline (T1), early on-treatment (T2), late on-treatment (T3) and 3-months post-treatment (T4). PRO mean change scores were calculated from baseline and a minimally important change (MIC) threshold was set at 5%. Regression analyses investigated patient and treatment characteristics independently associated with PRO changes on-treatment and post-treatment.

Results: Of 1,564 patients, 55% were male, 39% non-white, 47% had cirrhosis. Sofosbuvir/ledipasvir was prescribed to 63%, sofosbuvir/velpatasvir to 21%, grazoprevir/elbasvir to 11%, and paritaprevir/ombitasvir/ritonavir + dasabuvir to 5%. During DAA therapy, mean PRO scores improved slightly in the overall cohort, but did not reach the 5% MIC threshold. Between 21-53% of patients experienced >5% improved PROs while 23-36% experienced >5% worse symptoms. Of 1,410 patients with evaluable sustained virologic response (SVR) data, 95% achieved SVR. Among those with SVR, all mean PRO scores improved, with the 5% MIC threshold met for fatigue, sleep disturbance, and functioning well-being. Regression analyses identified subgroups, defined by age 35-55, baseline mental health issues and a higher number of health comorbidities as predictors of PRO improvements.

Conclusions: In real-world clinical practices, we observed heterogeneous patient experiences during and after DAA treatment. Symptom improvements were more pronounced in younger patients, those with baseline mental health issues and multiple comorbidities.

Lay summary: Patients who received direct-acting antiviral medications for hepatitis C at several liver centers in the US did not generally experience significant changes in baseline symptoms during treatment. We observed a full range of patient experiences with some patients experiencing substantial symptom improvements, yet others experiencing less improvements and some even experiencing a worsening of symptoms. The 1,346 patients who were cured of hepatitis C experienced improvements in fatigue, sleep disturbance, and functional well-being, and trends for improved pain and depression; whereas the 64 who were not cured experienced minimal improvements. Clinicaltrial.gov: NCT02601820.

Keywords: Functioning; HCV; Liver; PRO; Pain; Patient-reported outcome; Quality of life; Sleep; Symptom; Treatment.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amides / therapeutic use
  • Anilides / therapeutic use
  • Antiviral Agents / therapeutic use*
  • Benzimidazoles
  • Benzofurans / therapeutic use
  • Carbamates / therapeutic use
  • Cyclopropanes / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Fluorenes
  • Hepacivirus / drug effects*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Heterocyclic Compounds, 4 or More Rings / therapeutic use
  • Humans
  • Imidazoles / therapeutic use
  • Macrocyclic Compounds / therapeutic use
  • Male
  • Middle Aged
  • Patient Reported Outcome Measures*
  • Prospective Studies
  • Quinoxalines / therapeutic use
  • Ritonavir / therapeutic use
  • Sofosbuvir / therapeutic use
  • Sulfonamides / therapeutic use
  • Sustained Virologic Response*
  • Uracil / analogs & derivatives
  • Uracil / therapeutic use
  • Young Adult

Substances

  • 2-(pyrrolidin-2-yl)-5-(2-(4-(5-(pyrrolidin-2-yl)-1H-imidazol-2-yl)phenyl)benzofuran-5-yl)-1H-imidazole
  • Amides
  • Anilides
  • Antiviral Agents
  • Benzimidazoles
  • Benzofurans
  • Carbamates
  • Cyclopropanes
  • Fluorenes
  • Heterocyclic Compounds, 4 or More Rings
  • Imidazoles
  • Macrocyclic Compounds
  • Quinoxalines
  • Sulfonamides
  • ledipasvir, sofosbuvir drug combination
  • ombitasvir
  • grazoprevir
  • Uracil
  • dasabuvir
  • velpatasvir
  • Ritonavir
  • paritaprevir
  • Sofosbuvir

Associated data

  • ClinicalTrials.gov/NCT02601820