Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, USA.
J Viral Hepat. 2022 Sep;29(9):795-806. doi: 10.1111/jvh.13716. Epub 2022 Jun 15.
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.
PRIORITIZE 试验（clinicaltrials.gov：NCT02786537）是第一项直接比较 ledipasvir/sofosbuvir（LDV/SOF）和 elbasvir/grazoprevir（EBR/GZR）治疗慢性丙型肝炎病毒（HCV）的比较疗效研究。该研究的次要目的是比较 LDV/SOF 和 EBR/GZR 在实现持续病毒学应答（SVR）的患者中对几种与 HCV 相关的症状和功能健康的可持续变化。PRIORITIZE 是一项 2016 年至 2020 年期间进行的随机对照试验，使用特定于疾病的 HCV-PRO 工具评估了六个 PROMIS®症状评分（疲劳、睡眠障碍、认知障碍、恶心、腹泻、腹痛）和功能健康的变化。在基线、早期治疗后（中位数=6 个月）和晚期治疗后（中位数=21 个月）进行了调查评估。使用约束性纵向线性混合效应模型评估治疗内变化和治疗间差异。对 793 名参与者（平均年龄 55 岁，57%为男性，44%为黑人，17%为肝硬化）的数据进行了分析。从基线到早期治疗后，5 项症状和功能健康均显著改善（所有 p 值均<.05）。在 LDV/SOF 组中，平均变化范围从恶心的-3.73 到疲劳的-6.41，在 EBR/GZR 组中，平均变化范围从认知障碍的-2.19 到疲劳的-4.67。变化超过 3 点被认为具有临床意义。大多数症状的改善略微有利于 LDV/SOF，尽管两种方案之间的差异幅度较小。两种方案均在晚期治疗阶段显示出持续的症状和功能健康的显著改善。在 SVR 后两年内，EBR/GZR 和 LDV/SOF 方案在 HCV 症状和功能健康方面具有临床等效且持久的改善。
