Cholangitis Induced by Immune Checkpoint Inhibitors: Analysis of Pharmacovigilance Data

Lucy Meunier; Lina Hountondji; Hélène Jantzem; Jean Luc Faillie; Alexandre Maria; Pascale Palassin; MonRIO Group

doi:10.1016/j.cgh.2023.12.008

Cholangitis Induced by Immune Checkpoint Inhibitors: Analysis of Pharmacovigilance Data

Clin Gastroenterol Hepatol. 2023 Dec 16:S1542-3565(23)01037-6. doi: 10.1016/j.cgh.2023.12.008. Online ahead of print.

Authors

Lucy Meunier¹, Lina Hountondji², Hélène Jantzem³, Jean Luc Faillie⁴, Alexandre Maria⁵, Pascale Palassin⁶; MonRIO Group

Collaborators

MonRIO Group:
Stéphanie Faure⁷, Philine Witkowski-Durand-Viel⁸, Xavier Quantin⁸, Georges Philippe Pageaux⁷

Affiliations

¹ Department of Hepatogastroenterology and Liver Transplantation, Universitary Hospital Centre Montpellier, University of Montpellier, Montpellier, France; Institute for Regenerative Medicine and Biotherapy, University of Montpellier, Montpellier, France.
² Department of Hepatogastroenterology and Liver Transplantation, Universitary Hospital Centre Montpellier, University of Montpellier, Montpellier, France.
³ Department of Pharmacovigilance, Universitary Hospital Centre Brest, Brest, France.
⁴ Department of Medical Pharmacology and Toxicology, Universitary Hospital Centre Montpellier, University of Montpellier, Montpellier, France; Desbrest Institute of Epidemiology and Public Health, INSERM, University of Montpellier, Montpellier, France.
⁵ Internal Medicine and Immuno-Oncology, Institute for Regenerative Medicine and Biotherapy, Universitary Hospital Centre Montpellier, University of Montpellier, Montpellier, France.
⁶ Department of Medical Pharmacology and Toxicology, Universitary Hospital Centre Montpellier, University of Montpellier, Montpellier, France.
⁷ Department of Heptogastroenterology and Liver Transplantation, Universitary Hospital Centre Montpellier, University of Montpellier, Montpellier, France.
⁸ Department of Medical Oncology, Montpellier Cancer Institute, Universitary Hospital Centre Montpellier, University of Montpellier, Montpellier, France.

PMID: 38110061
DOI: 10.1016/j.cgh.2023.12.008

Abstract

Immune checkpoint inhibitors (ICIs) are remarkable anticancer therapies that have revolutionized the oncological prognosis of many cancers.¹ The considerable efficacy of ICIs is associated with the onset of more- or less-serious, immune-related adverse effects (irAEs) affecting several organs, which can concern up to 70% of patients, owing to a loss of self-tolerance during the restoration of antitumor immunity.² Checkpoint inhibitor-induced liver injury (CHILI), which may occur in up to 25% of patients, is treated with steroids as first-line treatment, and immunosuppressive drugs as second-line treatment.³ Recently, ICI-induced cholangitis was described as an emerging irAE. Hence, Pi et al⁴ reviewed all 53 published cases of ICI-induced cholangitis and compared the different types of bile duct involvement. We recently described CHILI according to the biological profile: cholestatic, hepatocellular, or mixed.⁵ Cholestatic profiles were associated with macroscopic and/or microscopic bile duct damage, and time to resolution was significantly longer. More recently, Onoyama et al⁶ and Parlati et al⁷ described a poorer response to steroids in cases of biliary histologic damage or ICI-induced sclerosing cholangitis. The latest European Society for Medical Oncology guidelines include the management of cholangitis, which is succinct and still poorly documented.³ The aim of this study therefore was to analyze the cases of ICI-induced cholangitis reported in the French pharmacovigilance system to describe their clinical characteristics, evolution, and outcome.