TY - JOUR
T1 - Best practices for detection, assessment and management of suspected immune-mediated liver injury caused by immune checkpoint inhibitors during drug development
AU - Regev, Arie
AU - Avigan, Mark I.
AU - Kiazand, Alexandre
AU - Vierling, John M.
AU - Lewis, James H.
AU - Omokaro, Stephanie O.
AU - Di Bisceglie, Adrian M.
AU - Fontana, Robert J.
AU - Bonkovsky, Herbert L.
AU - Freston, James W.
AU - Uetrecht, Jack P.
AU - Miller, Ethan D.
AU - Pehlivanov, Nonko D.
AU - Haque, Syed Asif
AU - Harrison, Melanie J.
AU - Kullak-Ublick, Gerd A.
AU - Li, Hewei
AU - Patel, Niti N.
AU - Patwardhan, Meenal
AU - Price, Karen D.
AU - Watkins, Paul B.
AU - Chalasani, Naga P.
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - Checkpoint inhibitors
KW - Drug-development
KW - Drug-induced liver injury
KW - Immune-mediated liver injury
KW - Immunotherapy
UR - http://www.scopus.com/inward/record.url?scp=85089065340&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089065340&partnerID=8YFLogxK
U2 - 10.1016/j.jaut.2020.102514
DO - 10.1016/j.jaut.2020.102514
M3 - Review article
C2 - 32768244
AN - SCOPUS:85089065340
SN - 0896-8411
VL - 114
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
M1 - 102514
ER -