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Comprehensive Analysis of Detection Triggers for Immune-Related Adverse Events: Implications for Patient Education
Haruna Minami1, Ryosuke Matsukane1, Sai Yasukochi1
1Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
Purpose:
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.
Methods:
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).
Results:
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.
Conclusion:
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.
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