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

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.

Fig. 1.. Study flowchart

NOTE: DAC/SOF: daclatasvir/sofosbuvir, T1: baseline, T2: early on-treatment, T3: late on-treatment, T4: early post-treatment.

Fig. 2.. Mean PRO change scores at on-treatment and post-treatment in overall sample (n=1564)

NOTE: Unadjusted PRO change scores at the following time points are shown: Early On-Tx: Early Treatment Phase; Late On-Tx: Late Treatment Phase; Post-Tx: Early Post-Treatment. DAA: Direct-Acting Antiviral. MIC: Minimally Important Change defined as > 5% change in PRO score suggests clinically significant change. The 5% MIC threshold for the PROMIS and Headache measures is ±2.5 points; the MIC for Functional Well-Being is ±4 points; the MIC for Overall Symptom Burden is ±3.0. Negative change scores=PRO score improved; Positive change scores=PRO score worsened. Missing values for all PROs were 4%−8% (functional well-being missing 14%−16%).

Fig. 3.. Proportion of patients whose symptoms stayed the same, improved or worsened during DAA therapy

NOTE: DAA: Direct-Acting Antiviral. Missing values for all PROs were 1%−3%, except Functional well-being was missing for 9% of patients. Improved ≥ 5% improvement from baseline; Worsened ≥ 5% worse from baseline score.

Fig. 4.. PRO mean change scores from baseline to early post-treatment by SVR status

NOTE: PRO mean change scores from Baseline to Early Post-Treatment (Early Post-Tx). CI: confidence interval; SVR: Sustained Virologic Response. For patients who achieved SVR, functional well-being change scores were missing for 13%−22% of patients; for the ten PRO measures, change scores were missing for 0% - 6% of patients. Among non-SVR patients, for all PRO measures, change scores were missing for 0% - 17% of patients.

Fig. 5.. Percent change in PRO scores from baseline to post-treatment by SVR status

NOTE: Percent change in PRO mean scores from Baseline to Early Post-Treatment (Early Post-Tx). Horizontal bars denotes 95% confidence intervals. *The lower limit of the 95% CI = −42 for Overall Symptom Burden in the Non-SVR group. Dotted vertical lines represent 5% MIC thresholds. SVR: Sustained Virologic Response. For patients who achieved SVR (n=1346), functional well-being change scores were missing for 15% of patients; for the ten PRO measures, change scores were missing for 0% - 5% of patients. For patients who did not achieve SVR (n=64), headache and functional well-being change scores were missing for 17% and 20% of patients, respectively; for the eight other PRO measures, change scores were missing for 0% - 13% of patients.