Comprehensive Analysis of Detection Triggers for Immune-Related Adverse Events: Implications for Patient Education and Management.

Abstract

With increasing use of immune checkpoint inhibitors (ICIs), effective management of immune-related adverse events (irAEs) has become a critical concern. This study aimed to identify the detection triggers of irAEs and provide insights for improving their management. This retrospective analysis included 1,237 patients treated with ICIs between 2014 and 2023. irAEs were categorized into three groups based on their detection triggers: symptom-dominant irAEs (>80% of cases identified through subjective symptoms), test-dominant irAEs (>80% of cases detected via clinical examinations), and mixed-type irAEs (meeting neither criterion). Among the 1,237 patients, 547 (44.2%) experienced 797 irAEs. Symptom-dominant irAEs included skin toxicity (all-grade: 17.3%, grade ≥3: 1.1%), colitis (3%, 1.4%), musculoskeletal toxicity (1.9%, 0.6%), type 1 diabetes (0.6%, 0.6%), nervous system toxicity (0.6%, 0.4%), and ocular toxicity (0.4%, 0%). Test-dominant irAEs included thyroid dysfunction (11.7%, 0.3%), hepatitis (6.5%, 3.2%), nephritis (1.9%, 0.4%), pancreatitis (1.5%, 1.1%), and hematological toxicity (0.6%, 0.3%). Mixed-type irAEs included pneumonitis (10.6%, 2.7%), adrenal insufficiency or hypophysitis (5.2%, 2.5%), and cardiovascular toxicity (0.8%, 0.2%). Mixed-type irAEs were associated with significantly higher rates of grade ≥3 events (33.2%) and unscheduled hospital visits (26.8%) than other irAEs. Furthermore, mixed-type irAEs identified through clinical examination generally exhibited milder severity than those detected based on subjective symptoms. Considering irAE detection triggers, incidence, and severity, this study highlights skin toxicity, colitis, pneumonitis, and adrenal insufficiency as high-priority conditions for patient education. After treatment initiation, test-dominant irAEs require appropriate diagnostic work-ups, symptom-dominant irAEs emphasize the importance of patient interviews, and mixed-type irAEs benefit from a combination of these strategies. This comprehensive strategy may improve irAE detection and management, ultimately enhancing patient outcomes.