Safety and Effectiveness Using 8 Weeks of Glecaprevir/Pibrentasvir in HCV-Infected Treatment-Naïve Patients with Compensated Cirrhosis: The CREST Study.

ABSTRACT

INTRODUCTION: In clinical trials with hepatitis C virus-infected treatment-naïve (TN) patients with compensated cirrhosis (CC), glecaprevir/pibrentasvir (G/P), a fixed-dose, once-daily, pangenotypic regimen, has demonstrated sustained virologic response at posttreatment Week 12 (SVR12) > 95%. We evaluated the real-world safety and effectiveness of 8-week G/P therapy in TN patients with CC, including certain subgroups of interest. METHODS: The CREST study is a real-world, noninterventional, multicenter study retrospectively assessing data from Canada, Germany, Israel, Italy, and Spain. The full analysis set (FAS) designated all patients in the study; the modified analysis set (MAS) excluded patients who discontinued G/P for nonvirologic failure or who had missing SVR12 data. The primary endpoint was SVR12; safety endpoints were also assessed. RESULTS: A total of 386 patients were included in the FAS, 375 patients completed the study, and 325 patients were included in the MAS; 51 patients had missing SVR12 data. Overall, in the MAS and FAS, SVR12 was achieved in 99.1% and 84.2% of patients, respectively. In subgroups of interest, the percentage of patients achieving SVR12 in the MAS (and FAS) was genotype (GT)3 97.5% (80.6%); FibroScan® ≥ 12.5 kPa 98.9% (89.3%); platelet count < 100 × 109/l 100% (88.2%); both platelets < 150 × 109/l and FibroScan® > 20 kPa 100% (88.9%); aspartate aminotransferase-to-platelet ratio index > 1.09 98.7% (83.1%); fibrosis-4 index > 3.25 98.6% (84.0%); albumin < 3 g/dl 100% (91.7%); people who use drugs 97.7% (84.3%); psychiatric disorders 96.6% (84.8%); and human immunodeficiency virus coinfection 100% (95.0%). Overall, 26.9% (104/386) of patients experienced an adverse event, none of which were classed as serious. CONCLUSION: In this real-world cohort, 8 weeks of G/P therapy was well tolerated in TN patients with CC. SVR12 rates were similar to clinical trials, supporting 8-week treatment in TN patients with CC, including those with signs of advanced liver disease and GT3 infection.