Jason Grebely1, Gregory J Dore2, Negar N Alami3, Brian Conway4, John F Dillon5, Michael Gschwantler6, Franco Felizarta7, Christophe Hézode8, Krzysztof Tomasiewicz9, Linda M Fredrick3, Emily O Dumas3, Federico J Mensa3. 1. The Kirby Institute, UNSW Sydney, Sydney, Australia. Electronic address: jgrebely@kirby.unsw.edu.au. 2. The Kirby Institute, UNSW Sydney, Sydney, Australia. 3. AbbVie, North Chicago, IL, USA. 4. Vancouver Infectious Diseases Centre, Vancouver, Canada. 5. Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, Dundee, UK. 6. Department of Internal Medicine IV, Wilhelminenspital, Vienna, Austria; Sigmund Freud University, Vienna, Austria. 7. Private Practice, Bakersfield, CA, USA. 8. Department of Hepatology, Hôpital Henri Mondor, Université Paris-Est, Paris, France. 9. Department of Infectious Diseases and Hepatology, Medical University of Lublin, Lublin, Poland.
Abstract
BACKGROUND: International guidelines recommend treatment of hepatitis C virus (HCV) infection in people who inject drugs (PWID), including those on opioid substitution therapy (OST). The pangenotypic combination of glecaprevir and pibrentasvir has shown high sustained virologic response at post-treatment Week 12 (SVR12) in clinical trials. Herein, we evaluate the safety and efficacy of glecaprevir/pibrentasvir in patients receiving OST. METHODS: Pooled data from patients with HCV genotypes 1-6 who were treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks in eight Phase 2 and 3 trials were categorized by use of OST. Treatment completion, treatment adherence, SVR12, adverse events (AEs), and laboratory abnormalities were evaluated for patients receiving and not receiving OST. RESULTS: Among 2256 patients, 157 (7%) were receiving OST. Compared with patients not receiving OST, OST patients were younger (mean age, 46.8 vs 52.8 years), male (69% vs 54%), white (93% vs 80%), HCV treatment-naïve (86% vs 72%), had HCV genotype 3 (60% vs 26%), and had a history of depression or bipolar disorder (43% vs 19%). Most patients completed (OST: 98% [n/N = 154/157]; non-OST: 99% [n/N = 2070/2099]) and were adherent (received ≥90% of study drug doses) to glecaprevir/pibrentasvir treatment (OST: 98% [n/N = 121/123]; non-OST: 99% [n/N = 1884/1905] among patients with available data). In the intention-to-treat population, SVR12 rates in OST and non-OST patients were 96.2% (n/N = 151/157; 95% CI 93.2-99.2) and 97.9% (n/N = 2055/2099; 95% CI 97.3-98.5), respectively. For OST patients, reasons for nonresponse included virologic relapse (<1%; n = 1), premature study drug discontinuation (<1%; n = 1), and loss to follow-up (3%; n = 4). AEs occurring in ≥10% of OST patients were headache, fatigue, and nausea. Drug-related serious AEs, AEs leading to study drug discontinuation, and Grade 3 or higher laboratory abnormalities were infrequent in both groups (<1%). No HCV reinfections occurred through post-treatment Week 12. CONCLUSION: Glecaprevir/pibrentasvir is highly efficacious and well tolerated in HCV-infected patients receiving OST.
BACKGROUND: International guidelines recommend treatment of hepatitis C virus (HCV) infection in people who inject drugs (PWID), including those on opioid substitution therapy (OST). The pangenotypic combination of glecaprevir and pibrentasvir has shown high sustained virologic response at post-treatment Week 12 (SVR12) in clinical trials. Herein, we evaluate the safety and efficacy of glecaprevir/pibrentasvir in patients receiving OST. METHODS: Pooled data from patients with HCV genotypes 1-6 who were treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks in eight Phase 2 and 3 trials were categorized by use of OST. Treatment completion, treatment adherence, SVR12, adverse events (AEs), and laboratory abnormalities were evaluated for patients receiving and not receiving OST. RESULTS: Among 2256 patients, 157 (7%) were receiving OST. Compared with patients not receiving OST, OST patients were younger (mean age, 46.8 vs 52.8 years), male (69% vs 54%), white (93% vs 80%), HCV treatment-naïve (86% vs 72%), had HCV genotype 3 (60% vs 26%), and had a history of depression or bipolar disorder (43% vs 19%). Most patients completed (OST: 98% [n/N = 154/157]; non-OST: 99% [n/N = 2070/2099]) and were adherent (received ≥90% of study drug doses) to glecaprevir/pibrentasvir treatment (OST: 98% [n/N = 121/123]; non-OST: 99% [n/N = 1884/1905] among patients with available data). In the intention-to-treat population, SVR12 rates in OST and non-OST patients were 96.2% (n/N = 151/157; 95% CI 93.2-99.2) and 97.9% (n/N = 2055/2099; 95% CI 97.3-98.5), respectively. For OST patients, reasons for nonresponse included virologic relapse (<1%; n = 1), premature study drug discontinuation (<1%; n = 1), and loss to follow-up (3%; n = 4). AEs occurring in ≥10% of OST patients were headache, fatigue, and nausea. Drug-related serious AEs, AEs leading to study drug discontinuation, and Grade 3 or higher laboratory abnormalities were infrequent in both groups (<1%). No HCV reinfections occurred through post-treatment Week 12. CONCLUSION:Glecaprevir/pibrentasvir is highly efficacious and well tolerated in HCV-infectedpatients receiving OST.
Authors: Edward Gane; Victor de Ledinghen; Douglas E Dylla; Giuliano Rizzardini; Mitchell L Shiffman; Stephen T Barclay; Jose Luis Calleja; Zhenyi Xue; Margaret Burroughs; Julio A Gutierrez Journal: J Viral Hepat Date: 2021-09-08 Impact factor: 3.517
Authors: Irene Pericot-Valverde; Moonseong Heo; Jiajing Niu; Brianna L Norton; Matthew J Akiyama; Linda Agyemang; Alain H Litwin Journal: Open Forum Infect Dis Date: 2020-10-10 Impact factor: 3.835