1. Best practices for detection, assessment and management of suspected immune-mediated liver injury caused by immune checkpoint inhibitors during drug development
- Author
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Naga Chalasani, Stephanie O. Omokaro, Syed Asif Haque, Herbert L. Bonkovsky, Nonko D. Pehlivanov, Adrian M. Di Bisceglie, Paul B. Watkins, Karen Price, James W. Freston, Mark I. Avigan, Hewei Li, Melanie J. Harrison, Arie Regev, John M. Vierling, Gerd A. Kullak-Ublick, Ethan Miller, James H. Lewis, Niti N. Patel, Jack Uetrecht, Alexandre Kiazand, Meenal Patwardhan, Robert J. Fontana, University of Zurich, Regev, Arie, and Chalasani, Naga P
- Subjects
0301 basic medicine ,Drug ,medicine.medical_specialty ,media_common.quotation_subject ,Immunology ,Psychological intervention ,610 Medicine & health ,03 medical and health sciences ,0302 clinical medicine ,Drug Development ,Liver Function Tests ,Neoplasms ,medicine ,Immunology and Allergy ,Animals ,Humans ,Intensive care medicine ,Adverse effect ,Immune Checkpoint Inhibitors ,media_common ,030203 arthritis & rheumatology ,2403 Immunology ,Mechanism (biology) ,business.industry ,Disease Management ,Discontinuation ,Clinical trial ,030104 developmental biology ,Drug development ,10199 Clinic for Clinical Pharmacology and Toxicology ,Inclusion and exclusion criteria ,2723 Immunology and Allergy ,Disease Susceptibility ,Chemical and Drug Induced Liver Injury ,business - Abstract
Immune checkpoint inhibitors (ICIs) have shown significant efficacy in patients with various malignancies, however, they are associated with a wide range of immune-related toxicities affecting many organs, including the liver. Immune-mediated liver injury caused by checkpoint inhibitors (ILICI) is a distinctive form of drug induced liver injury (DILI), that differs from most DILI types in presumed underlying mechanism, incidence, and response to therapeutic interventions. Despite increased awareness of ILICI and other immune-related adverse effects of ICIs reflected by recent guidelines for their management in post marketing clinical practice, there is lack of uniform best practices to address ILICI risk during drug development. As efforts to develop safer and more effective ICIs for additional indications grow, and as combination therapies including ICIs are increasingly investigated, there is a growing need for consistent practices for ILICI in drug development. This publication summarizes current best practices to optimize the monitoring, diagnosis, assessment, and management of suspected ILICI in clinical trials using ICI as a single agent and in combination with other ICIs or other oncological agents. It is one of several publications developed by the IQ DILI Initiative in collaboration with DILI experts from academia and regulatory agencies. Recommended best practices are outlined pertaining to hepatic inclusion and exclusion criteria, monitoring of liver tests, ILICI detection, approach to a suspected ILICI signal, causality assessment, hepatic discontinuation rules and additional medical treatment.
- Published
- 2020