Sustainable and Equivalent Improvements in Symptoms and Functional Well-being Following Viral Cure From Ledipasvir/Sofosbuvir Versus Elbasvir/Grazoprevir for Chronic Hepatitis C Infection

Findings From The Randomized Prioritize Trial

Donna M. Evon; Meichen Dong; Bryce B. Reeve; Joy Peter; Larry Michael; Anna S. Lok; David R. Nelson; Paul W. Stewart

Disclosures

J Viral Hepat. 2022;29(9):795-806. 

In This Article

Abstract and Introduction

Abstract

The PRIORITIZE trial (clinicaltrials.gov: NCT02786537) was the first comparative effectiveness study to directly compare ledipasvir/sofosbuvir (LDV/SOF) and elbasvir/grazoprevir (EBR/GZR) for the treatment of chronic hepatitis C virus (HCV). A secondary aim of this study was to compare LDV/SOF and EBR/GZR on sustainable changes in several HCV-associated symptoms and functional well-being in patients who achieved sustained virological response (SVR). PRIORITIZE, a randomized controlled trial conducted between 2016 and 2020, evaluated change in six PROMIS® symptom scores (fatigue, sleep disturbance, cognitive disturbance, nausea, diarrhoea, abdominal pain) and functional well-being using the disease-specific HCV-PRO instrument. Survey assessments were administered at baseline, early post-treatment (median = 6 months) and late post-treatment (median = 21 months). Constrained longitudinal linear mixed-effects models were used to evaluate within-treatment change and between-treatment differences. Data from 793 participants (average 55 years old, 57% male, 44% black, 17% with cirrhosis) were analysed. From baseline to early post-treatment, 5 out of 6 symptoms and functional well-being significantly improved (all p's < .05). In the LDV/SOF arm, mean changes ranged from −3.73 for nausea to −6.41 for fatigue and in the EBR/GZR, mean changes ranged from −2.19 for cognitive impairment to −4.67 for fatigue. Change of >3 points was consider clinically meaningful. Improvements in most symptoms slightly favoured LDV/SOF, although the magnitude of differences between the regimens were small. Both regimens demonstrated significant improvements in symptoms and functional well-being that were sustained during the late post-treatment phase. EBR/GZR and LDV/SOF regimens had clinically equivalent and durable improvements in HCV symptoms and functional well-being up to two years after SVR.

Introduction

Individuals living with chronic hepatitis C virus (HCV) infection often complain of debilitating or bothersome symptoms such as fatigue, depression, anxiety, cognitive dysfunction, sleep disturbance, aches and pains and gastrointestinal symptoms that are associated with poor health-related quality of life (HRQOL).[1–4] HCV can cause inflammatory and immune abnormalities early during the infection even prior to cirrhosis and can lead to extrahepatic manifestations that may be partially responsible for chronic symptoms.[5–10]

All-oral, direct acting antiviral (DAA) regimens can eradicate HCV in approximately 95% of patients treated.[11] Phase III registration trials of DAA medications did not use active comparator groups but rather compared regimens to historical controls or within DAA trials, to regimens with and without ribavirin (RBV).[12,13] Achieving viral cure has been associated with improvements in symptoms and HRQOL in registration trials and in uncontrolled observational studies.[14–16] Despite widespread global use of several different DAA regimens, comparative effectiveness studies that directly compare different DAAs on patient-centred outcomes have not been conducted until recently. Results from the PRIORITIZE study, the only randomized controlled trial to compare efficacy and tolerability of different DAA regimens, recently demonstrated equivalence between DAA regimens on treatment efficacy, safety, and drug side effect profiles.[17] Beyond sustained virological response (SVR) rates, other characteristics of treatment matter to patients and stakeholders, such as the magnitude and durability of improvements in HCV symptoms and functioning.[18] Whether differences exist between DAA regimens in terms of amelioration of HCV-associated symptoms or improvements in functioning following SVR, both in the short term and the long term, has not been determined, but would provide valuable data for patients, clinicians and other stakeholders.

The objective of this longitudinal study was to provide a direct comparison of improvements in HCV symptoms and functional well-being up to two years after SVR, in patients with genotype 1 HCV who were treated with ledipasvir/sofosbuvir (LDV/SOF) or elbasvir/grazoprevir (EBR/GZR) in the PRIORITIZE trial.[17]

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