Efficacy and safety of glecaprevir/pibrentasvir in patients with chronic HCV infection and psychiatric disorders: An integrated analysis

David Back, Pamela Belperio, Mark Bondin, Francesco Negro, Andrew H Talal, Caroline Park, ZhenZhen Zhang, Brett Pinsky, Eric Crown, Federico J Mensa, Fiona Marra, David Back, Pamela Belperio, Mark Bondin, Francesco Negro, Andrew H Talal, Caroline Park, ZhenZhen Zhang, Brett Pinsky, Eric Crown, Federico J Mensa, Fiona Marra

Abstract

Although direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection are highly efficacious and safe, treatment initiation is often limited in patients with neuropsychiatric disorders due to concerns over reduced treatment adherence and drug-drug interactions. Here, we report adherence, efficacy, safety and patient-reported outcomes (PROs) from an integrated analysis of registrational studies using the pangenotypic DAA regimen of glecaprevir and pibrentasvir (G/P). Patients with chronic HCV genotypes 1-6 infection with compensated liver disease (with or without cirrhosis) receiving G/P for 8, 12 or 16 weeks were included in this analysis. Patients were classified as having a psychiatric disorder based on medical history and/or co-medications. Primary analyses assessed treatment adherence, efficacy (sustained virologic response at post-treatment week 12; SVR12), safety and PROs. Among 2522 patients receiving G/P, 789 (31%) had a psychiatric disorder with the most common diagnoses being depression (64%; 506/789) and anxiety disorders (27%; 216/789). Treatment adherence was comparably high (>95%) in patients with and without psychiatric disorders. SVR12 rates were 97.3% (768/789; 95% CI = 96.2-98.5) and 97.5% (1689/1733; 95% CI = 96.7-98.2) in patients with and without psychiatric disorders, respectively. Among patients with psychiatric disorders, SVR12 rates remained >96% by individual psychiatric diagnoses and co-medication classes. Overall, most adverse events (AEs) were mild-to-moderate in severity with serious AEs and AEs leading to G/P discontinuation occurring at similarly low rates in both patient populations. In conclusion, G/P treatment was highly efficacious, well-tolerated and demonstrated high adherence rates in patients with chronic HCV infection and psychiatric disorders.

Trial registration: ClinicalTrials.gov NCT02243280 NCT02243293 NCT02604017 NCT02640482 NCT02640157 NCT02636595 NCT02642432 NCT02651194 NCT02446717 NCT02738138.

Keywords: chronic hepatitis C; drug interactions; mental disorders; sustained virologic response; treatment adherence and compliance.

Conflict of interest statement

David Back: Advisory board member/speakers bureau and receives honorarium from: Gilead, Merck, AbbVie, Bristol‐Myers Squibb, Janssen; received research grant funding from: Gilead, Merck, AbbVie, Bristol‐Myers Squibb, Janssen; received travel sponsorship from: AbbVie. Pamela Belperio: Nothing to disclose. Fiona Marra: consulting or grants from AbbVie, Gilead, Merck, Janssen and Viiv. Francesco Negro: advisor to Gilead, AbbVie, Merck. Unrestricted research grant from AbbVie. Investigator initiated study supported by Gilead. Andrew Talal: Research grants: AbbVie, Merck, Gilead, Intercept, Conatus, Abbott, Genfit, Center for AIDS Research, Patient‐Centered Outcomes Research Institute (PCORI); Advisor: AbbVie, Merck, Abbott Diagnostics, Chronic Liver Disease Foundation; Speaker's Bureau: Chronic Liver Disease Foundation. Mark Bondin, Caroline Park, ZhenZhen Zhang, Brett Pinsky, Federico Mensa, Eric Crown are employees of AbbVie, Inc and may hold stock or stock options.

© 2019 The Authors. Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
SVR12 by ITT analysis for patients with and without a psychiatric disorder. G/P efficacy, defined as SVR12, is reported both overall and by presence or absence of psychiatric disorders. Reasons for nonresponse are reported for virologic (breakthrough or relapse) and nonvirologic (discontinuation or lost to follow‐up) failure
Figure 2
Figure 2
SVR12 by ITT analysis stratified by psychiatric diagnosis or neuropsychiatric co‐medication for patients with psychiatric disorders. SVR12 data in patients with psychiatric disorders further stratified by individual psychiatric disorders (light blue) or neuropsychiatric co‐medications (blue)

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