Safety of Patients with Hepatitis C Virus Treated with Glecaprevir/Pibrentasvir from Clinical Trials and Real-World Cohorts

Abstract

Introduction: More than 70 million people are estimated to be infected with hepatitis C virus (HCV) globally. If left untreated, HCV infection can lead to complications such as extensive liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Evolution of treatments has resulted in highly effective and well-tolerated all-oral direct-acting antivirals. The pangenotypic regimen of glecaprevir/pibrentasvir is approved for treating HCV for patients without cirrhosis or with compensated cirrhosis (CC). Guidelines have evolved to simplify treatment to enable non-specialists to manage and treat HCV-infected patients. Simultaneously, such treatment algorithms provide guidance on the pretreatment identification of small subsets of patients who may require specialist treatment and long-term follow-up for advanced liver disease, including those at risk of developing HCC. This study describes the safety profile of glecaprevir/pibrentasvir in patients identified using previously described noninvasive laboratory measures who may be eligible for treatment by non-liver specialists.

Methods: This post hoc analysis of glecaprevir/pibrentasvir in patients, identified by noninvasive laboratory measures, intended to exclude patients with advanced liver disease and severe renal impairment, who can be managed within non-liver specialist settings. Patients were included from clinical trials and real-world studies of glecaprevir/pibrentasvir for HCV treatment. Baseline demographics, clinical characteristics, and safety assessments, including adverse events and laboratory abnormalities, were summarized.

Results: Data across these large-scale studies confirm that glecaprevir/pibrentasvir is well tolerated across different patient populations, with fewer than 0.1% of patients experiencing a serious adverse event related to treatment drugs, and few patients developing HCC during or after treatment.

Conclusion: The safety profile of glecaprevir/pibrentasvir enhances the confidence of non-liver specialists to treat the majority of HCV-infected patients, and provides an opportunity to expand the treater pool, potentially increasing diagnosis and treatment rates for HCV, contributing to elimination of HCV.

Keywords: Hepatitis C virus; Non-specialist; Safety.

Fig. 1

SVR12 rates in the patient populations in the clinical trial cohort (a) and PMOS cohort (b). CPSFU population included patients from the core population, excluding those who did not have an HCV RNA evaluation after posttreatment day 70 for reasons not related to effectiveness or safety (lost to follow-up or unavailable HCV RNA data). Patients included in the CPSFU had one of the following: HCV RNA data after posttreatment day 70 (not included if the drug end date was unknown), virologic failure (on-treatment virologic failure or posttreatment relapse), discontinued the study because of an AE, and had HCV RNA < 50 IU/mL at the last measurement. mITT population excluded patients who did not achieve SVR for reasons other than virologic failure (e.g., patients who discontinued early or were lost to follow-up). AE adverse event, CPSFU core population with sufficient follow-up, FIB-4 Fibrosis-4 score, HCV hepatitis C virus, ITT intention-to-treat, mITT modified intention-to-treat, PMOS post-marketing observation studies, RNA ribonucleic acid, SVR12 sustained virologic response at posttreatment week 12. FibroScan^® is a product of Echosens (Waltham, MA)