Real-world effectiveness and safety of glecaprevir/pibrentasvir in 723 patients with chronic hepatitis C

Roberta D'Ambrosio, Luisa Pasulo, Massimo Puoti, Maria Vinci, Monica Schiavini, Sergio Lazzaroni, Alessandro Soria, Federico Gatti, Barbara Menzaghi, Alessio Aghemo, Francesca Capelli, Maria Grazia Rumi, Lorenzo Morini, Alessia Giorgini, Marie Graciella Pigozzi, Angelo Rossini, Franco Maggiolo, Angelo Pan, Massimo Memoli, Ombretta SpinelliPaolo Del Poggio, Valeria Saladino, Angiola Spinetti, Anna De Bona, Andrea Capretti, Caterina Uberti-Foppa, Paolo Bonfanti, Natalia Terreni, Fernanda Menozzi, Alberto Eraldo Colombo, Omar Giglio, Riccardo Centenaro, Marta Borghi, Chiara Baiguera, Viviana Picciotto, Simona Landonio, Andrea Gori, Carlo Magnani, Franco Noventa, Stefania Paolucci, Pietro Lampertico, Stefano Fagiuoli, NAVIGATORE-Lombardia Study Group

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Abstract

BACKGROUND AND AIMS: The efficacy and safety of glecaprevir/pibrentasvir (G/P) for patients infected with hepatitis C virus (HCV) have only been investigated in clinical trials, with no real-world data currently available. The aim of our study was to investigate the effectiveness and safety of G/P in a real-world setting. METHODS: All patients with HCV consecutively starting G/P between October 2017 and January 2018 within the NAVIGATORE-Lombardia Network were analyzed. G/P was administered according to drug label (8, 12 or 16 weeks). Fibrosis was staged either histologically or by liver stiffness measurement. Sustained virological response (SVR) was defined as undetectable HCV-RNA 12 weeks after the end of treatment. RESULTS: A total of 723 patients (50% males) were treated with G/P, 89% for 8 weeks. The median age of our cohort was 58 years, with a median body mass index of 23.9 kg/m(2), and median liver stiffness measurement of 6.1 kPa; 84% were F0-2 and 16% were interferon-experienced. Median HCV-RNA was 1,102,600 IU/ml, and 49% of patients had HCV genotype 1 (32% 1b), 28% genotype 2, 10% genotype 3 and 13% genotype 4. The median estimated glomerular filtration rate was 90.2 ml/min, platelet count 209x10(3)/mm(3) and albumin 4.3 g/dl. The SVR rates were 94% in intention-to-treat and 99.3% in per protocol analysis (8-week vs. 12 or 16-week: 99.2% vs. 100%). Five patients failed therapy because of post-treatment relapse; a post-treatment NS5A resistance-associated substitution was detected in 1 case. SVR rates were lower in males (p = 0.002) and in HCV genotype-3 (p = 0.046) patients treated for 8 weeks, but independent of treatment duration, fibrosis stage, baseline HCV-RNA, HIV co-infection, chronic kidney disease stage and viral kinetics. Mild adverse events were reported in 8.3% of the patients, and 0.7% of them prematurely withdrew treatment. Three patients died of drug-unrelated causes. CONCLUSIONS: In a large real-world cohort of Italian patients, we confirmed the excellent effectiveness and safety of G/P administered for 8, 12 or 16 weeks. LAY SUMMARY: A large number of patients with hepatitis C virus have been treated with glecaprevir/pibrentasvir (G/P) within the NAVIGATORE-Lombardia Network, in Italy. This is the first real-world study evaluating effectiveness and safety of G/P in patients with hepatitis C virus treated according to international recommendations. This study demonstrated excellent effectiveness (with sustained virological response rates of 99.3%) and safety profiles.
Original languageEnglish
Pages (from-to)379-387
Number of pages9
JournalJournal of Hepatology
Volume70
Issue number3
DOIs
Publication statusPublished - Mar 2019

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Keywords

  • DAA
  • Effectiveness
  • Glecaprevir
  • HCV
  • Pibrentasvir
  • RAS
  • Real-life
  • SVR
  • Safety

Cite this

D'Ambrosio, R., Pasulo, L., Puoti, M., Vinci, M., Schiavini, M., Lazzaroni, S., Soria, A., Gatti, F., Menzaghi, B., Aghemo, A., Capelli, F., Rumi, M. G., Morini, L., Giorgini, A., Pigozzi, M. G., Rossini, A., Maggiolo, F., Pan, A., Memoli, M., ... Group, NAVIGATORE-L. S. (2019). Real-world effectiveness and safety of glecaprevir/pibrentasvir in 723 patients with chronic hepatitis C. Journal of Hepatology, 70(3), 379-387. https://doi.org/10.1016/j.jhep.2018.11.011