Sex differences in thyroid dysfunction onset timing induced by immune checkpoint inhibitors: JADER disproportionality...

Area of Science:

• Oncology
• Endocrinology
• Pharmacovigilance

Background:

• Immune checkpoint inhibitors (ICIs) are crucial in cancer therapy but can lead to thyroid dysfunction.
• The incidence of ICI-induced thyroid dysfunction (ICI-TD) is known, but its onset timing and sex differences are not well understood.

Purpose of the Study:

• To investigate the time to onset of thyroid dysfunction associated with specific ICIs (nivolumab, pembrolizumab, ipilimumab).
• To explore potential sex differences in the onset timing of ICI-TD.

Main Methods:

• Utilized the Japanese Adverse Drug Event Report (JADER) database to identify ICI-TD cases.
• Employed standardized MedDRA queries for case identification and calculated reporting odds ratios.
• Performed time-to-onset analysis using Weibull distribution and Mann-Whitney U-test, stratified by sex.

Main Results:

• Identified a significant number of ICI-TD cases across the studied drugs.
• Median onset times for hyperthyroidism ranged from 33 to 44.5 days and for hypothyroidism from 60 to 85 days.
• Onset of ICI-TD was consistently shorter in female patients compared to males.

Conclusions:

• ICI-induced thyroid dysfunction manifests earlier in female patients.
• Sex-specific monitoring strategies are essential for early detection and management of thyroid-related adverse events in patients undergoing ICI therapy.