Adverse Events of Hepatic Anti-Fibrotic Agents in Phase 3 and Above Clinical Trials

Liver fibrosis, a pathological response to chronic liver injuries, currently lacks FDA-approved pharmacotherapy. Despite advances in understanding hepatic fibrogenesis and the development of promising anti-fibrotic agents, adverse drug reactions (ADRs) pose significant challenges to their efficacy and clinical applicability. This study focuses on assessing ADRs associated with anti-fibrotic agents, utilizing data from the World Health Organization (WHO) VigiAccess database.

Methods: The research involved a detailed search on ClinicalTrial.gov to identify phase 3 or 4 clinical trials of hepatic anti-fibrotic agents. ADR reports were retrieved from the WHO-VigiAccess database, with data analyzed based on demographic characteristics, geographic distribution, and System Organ Classes (SOCs). Descriptive analysis identified the most frequently reported ADRs, while disproportionality analysis, measured by reporting odd ratio (ROR) and proportional report ratio (PRR), evaluated ADRs related to gastrointestinal disorders.

Results: Five hepatic anti-fibrotic agents—empagliflozin, liraglutide, candesartan, obeticholic acid, and resmetirom—were identified. Analysis of 130,567 ADR reports revealed that empagliflozin, liraglutide, and candesartan were associated with significantly higher ADRs. The most frequently reported SOCs included gastrointestinal disorders (29.44%), general disorders (24.12%), and nervous system disorders (14.42%). Notably, liraglutide demonstrated a higher risk of adverse reactions.

This study underscores the importance of monitoring and managing ADRs in the development and application of hepatic anti-fibrotic agents to optimize therapeutic strategies for liver fibrosis.