Time to use the right classification to predict the severity of checkpoint inhibitor‐induced liver injury, as assessed for causality using the updated RUCAM

• Published in: Alimentary pharmacology & therapeutics 2024-12, Vol.60 (11-12), p.1561-1572
• Main Authors: Hountondji, Lina, Faure, Stéphanie, Palassin, Pascale, Viel, Philine Witkowski Durand, Dupuy, Marie, Larrey, Dominique, Lamoureux, Anouck, Coustal, Cyrille, Pureur, Dimitri, Lesage, Candice, Assenat, Éric, Rivière, Benjamin, Faillie, Jean‐Luc, Quantin, Xavier, Pageaux, Georges‐Philippe, Maria, Alexandre Thibault Jacques, Meunier, Lucy
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Cancer therapies; Causality; Chemical and Drug Induced Liver Injury - classification; Chemical and Drug Induced Liver Injury - diagnosis; Chemical and Drug Induced Liver Injury - etiology; Classification; Classifying Checkpoint Inhibitor‐induced Liver Injury; Female; Hepatitis; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - adverse effects; Immunotherapy; Jaundice; Liver; Liver cancer; Liver diseases; Male; Middle Aged; Neoplasms - drug therapy; Original; Patients; Retrospective Studies; Severity of Illness Index
• ISSN: 0269-2813; 1365-2036; 1365-2036
• DOI: 10.1111/apt.18276

Summary Background and Aims While immune checkpoint inhibitors (ICIs) are revolutionising cancer therapy, checkpoint inhibitor‐induced liver injury is a significant immune‐related side effect of this immunotherapy. This study focuses on the severity classifications and characteristics of patients with checkpoint inhibitor‐induced hepatitis. Methods A retrospective analysis of patients with severe Checkpoint Inhibitor‐induced hepatitis grade 3 and 4 according to the recommended Common Terminology Criteria for Adverse Events (CTCAE) classification was conducted. Data on clinicobiological characteristics, treatment and outcomes were collected from 3 university hospitals, and causality was assessed by using the updated Roussel Uclaf Causality Assessment Method. The severity of hepatitis was assessed using the Model for End‐stage Liver Disease score, the Drug‐Induced Liver Injury Network, and the Drug‐Induced Liver Injury International Expert Working Group classifications. Results We retrospectively included 100 patients presenting various hepatitis patterns with a median time to onset of 20 days after checkpoint inhibitors. Severity grading varied significantly among the classifications used. A lower incidence of severe cases was observed when using the Drug‐Induced Liver Injury classifications instead of the recommended CCTCAE classification, and this was correlated with outcomes. Conclusions This retrospective study challenges the efficacy of the CTCAE classification in defining the severity of Checkpoint Inhibitor‐induced hepatitis and suggests that the traditional hepatology‐focused scores may be more relevant. The CTCAE classification is inconsistent and gives equal weight to jaundice and elevated transaminases, which leads to steroid overtreatment and limits the rechallenge of ICIs. The recommended classification Common Terminology Criteria for Adverse Events gives equal weight to jaundice and elevated transaminases and is inconsistent with the actual severity of checkpoint inhibitor‐induced hepatitis.