Effectiveness of 8-Week Glecaprevir/Pibrentasvir for Treatment-Naïve, Compensated Cirrhotic Patients with Chronic Hepatitis C Infection

Abstract

Introduction Glecaprevir/pibrentasvir (G/P) was approved on 26 September 2019 by the US Food and Drug Administration for 8-week duration in treatment-naïve (TN) hepatitis C virus (HCV)-infected patients with compensated cirrhosis (CC). Evidence from the EXPEDITION-8 study demonstrated that 8 weeks of G/P achieved a 98% intent-to-treat (ITT) sustained virologic response rate 12 weeks post treatment (SVR12) in 343 TN/CC patients. The aim of this study is to demonstrate the first US real-world effectiveness of G/P 8-week treatment in genotype 1–6 TN/CC HCV patients. Methods Data from 73 TN/CC patients who initiated 8 weeks of G/P treatment between August 2017 and November 2018 were collected electronically from providers and specialty pharmacies of the Trio Health network and analyzed. Cirrhosis was determined by FIB-4 > 5.2 or was physician reported. The primary outcome was Per Protocol (PP) SVR12. Results The majority (60%) of patients were male, with (mean values): age 59 years, body mass index (BMI) of 30, aspartate aminotransferase (AST) 105, and alanine aminotransferase (ALT) 101 IU/ml. HCV genotypes (GT) were: GT1 81% (59/73), GT2 10% (7/73), GT3 5% (4/73), GT4 3% (2/73), and GT6 1% (1/73). Eight percent (6/73) of patients had concurrent proton pump inhibitor (PPI) use, and 15% (11/72) had a baseline viral load > 6 MM IU/ml. Zero patients discontinued, two patients were reported as lost to follow-up, and there was one virologic failure. PP sustained virologic response at 12 weeks (SVR12) rate was 99% (70/71), and the intent-to-treat (ITT) SVR12 rate was 96% (70/73). Conclusions Early real-world experience indicates high effectiveness of the 8-week G/P regimen in a diverse treatment-naïve, compensated cirrhotic US population.

Real-World Clinical Practice Use of 8-Week Glecaprevir/Pibrentasvir in Treatment-Naïve Patients with Compensated Cirrhosis

“…Data from a total of seven studies are presented: global PMOS [ 11 ], DHC-R [ 14 ], Scottish HCV [ 12 ], Italian MISTRAL [ 13 ], Italian NAVIGATORE [ 15 ], US TRIO Health Analytics [ 16 ], and US VA [ 17 ], with additional 8-week TN CC-specific data provided for inclusion in this review. Baseline patient demographics and clinical characteristics, including GT and fibrosis stage, are presented in Table 1 .…”

“…Epidemiology estimates suggest that as many as 98% of TN patients with HCV would have no cirrhosis or CC and therefore could be treated with, and are amenable to, the 8-week regimen [21]. In the USA, TN patients without cirrhosis and with CC represent 98% of the HCV patient population [16]; therefore, the majority of patients are eligible for 8-week treatment.…”

“…Epidemiology estimates suggest that as many as 98% of TN patients with HCV would have no cirrhosis or CC and therefore could be treated with, and are amenable to, the 8-week regimen [ 21 ]. In the USA, TN patients without cirrhosis and with CC represent 98% of the HCV patient population [ 16 ]; therefore, the majority of patients are eligible for 8-week treatment. Although similar high SVR12 rates are observed for the 12-week G/P regimen, patients may prefer a shorter duration because it is more convenient and requires less monitoring [ 9 ].…”

“…The DHC-R [ 14 ] used the modified ITT (mITT) population, which excluded patients lost to follow-up. The Italian NAVIGATORE [ 15 ], US TRIO Health Analytics [ 16 ], and US Department of Veterans Affairs (VA) [ 17 ] studies used the per-protocol (PP) population, which included patients who completed treatment. Safety profile, in terms of deaths and adverse events (AEs) where available, were assessed in TN patients with CC treated with G/P for 8 weeks.…”

Letter: now is the time to remove complexity from HCV guidelines to ensure that elimination remains a priority

“…Published GLE/PIB real-world data in GT3 patients with compensated cirrhosis are limited to experience from the US Trio Health Network where only four patients were included. 5 In contrast, high cure rates have been demonstrated with sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks in over 330 GT3 patients with compensated cirrhosis in clinical studies and supported by extensive real-world experience, including in patients with advanced cirrhosis and portal hypertension ( Table 1). [6][7][8][9] Recently, 97% of the 324 cirrhotic GT3 patients in a global cohort were cured, irrespective of RAS testing.…”