TY - JOUR
T1 - Fractures Associated with Immune Checkpoint Inhibitors
T2 - A Disproportionality Analysis of the World Health Organization Pharmacovigilance Database
AU - Koseki, Takenao
AU - Hamano, Hirofumi
AU - Hatano, Masakazu
AU - Tobe, Takao
AU - Ieda, Ryo
AU - Nakai, Tsuyoshi
AU - Zamami, Yoshito
AU - Yamada, Shigeki
N1 - Publisher Copyright:
© 2025 by the authors.
PY - 2025/3
Y1 - 2025/3
N2 - Background/Objectives: The risk of fractures associated with immune checkpoint inhibitors (ICIs) is increasing; however, the relationship between fracture risk and potential factors, such as osteoporosis and hyperthyroidism, remains unclear. Methods: Using VigiBase, the World Health Organization’s global pharmacovigilance database, we investigated the signals for osteoporosis, hyperthyroidism, and fractures associated with ICIs (nivolumab, pembrolizumab, atezolizumab, durvalumab, ipilimumab, and tremelimumab) by calculating information components (ICs) and their 95% confidence intervals (CIs). Furthermore, we estimated the association between the occurrence of fractures in patients receiving ICIs and osteoporosis or hyperthyroidism. Results: Signals of hyperthyroidism (IC = 4.66, 95% CI: 4.58–4.73), but not osteoporosis (IC = −1.79, 95% CI: −2.22 to −1.36) or fractures (IC = −0.21, 95% CI: −0.36 to −0.06), were detected in patients using ICIs. Osteoporosis (odds ratio: 118.00, 95% CI: 61.00–230.00) was associated with an increased reporting frequency of fractures related to ICIs, whereas hyperthyroidism (odds ratio: 0.60, 95% CI: 0.19–1.87) was not associated with such an increase. Conclusions: The VigiBase analysis indicates that the use of ICIs does not increase the reporting frequency of osteoporosis or fractures. Additionally, hyperthyroidism did not increase the reporting frequency of fractures associated with ICIs.
AB - Background/Objectives: The risk of fractures associated with immune checkpoint inhibitors (ICIs) is increasing; however, the relationship between fracture risk and potential factors, such as osteoporosis and hyperthyroidism, remains unclear. Methods: Using VigiBase, the World Health Organization’s global pharmacovigilance database, we investigated the signals for osteoporosis, hyperthyroidism, and fractures associated with ICIs (nivolumab, pembrolizumab, atezolizumab, durvalumab, ipilimumab, and tremelimumab) by calculating information components (ICs) and their 95% confidence intervals (CIs). Furthermore, we estimated the association between the occurrence of fractures in patients receiving ICIs and osteoporosis or hyperthyroidism. Results: Signals of hyperthyroidism (IC = 4.66, 95% CI: 4.58–4.73), but not osteoporosis (IC = −1.79, 95% CI: −2.22 to −1.36) or fractures (IC = −0.21, 95% CI: −0.36 to −0.06), were detected in patients using ICIs. Osteoporosis (odds ratio: 118.00, 95% CI: 61.00–230.00) was associated with an increased reporting frequency of fractures related to ICIs, whereas hyperthyroidism (odds ratio: 0.60, 95% CI: 0.19–1.87) was not associated with such an increase. Conclusions: The VigiBase analysis indicates that the use of ICIs does not increase the reporting frequency of osteoporosis or fractures. Additionally, hyperthyroidism did not increase the reporting frequency of fractures associated with ICIs.
KW - VigiBase
KW - disproportionality analysis
KW - fractures
KW - hyperthyroidism
KW - immune checkpoint inhibitors
KW - osteoporosis
KW - pharmacovigilance
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U2 - 10.3390/ph18030333
DO - 10.3390/ph18030333
M3 - Article
AN - SCOPUS:105000910629
SN - 1424-8247
VL - 18
JO - Pharmaceuticals
JF - Pharmaceuticals
IS - 3
M1 - 333
ER -