Body Weight-Associated Differences in Adverse Drug Reaction Profiles of Aromatase Inhibitors: A Real-World Pharmacovigilance Study Using FAERS Database
Author(s)
Jeong-Hwa Yoon, PhD1, Hyo Jung Kim, PhD2, Yeon Hee Park, PhD3.
1Medical Research Center, Seoul National University, Seoul, Korea, Republic of, 2Department of Biomedical Software Engineering, The Catholic University of Korea, Bucheon, Korea, Republic of, 3Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of.
1Medical Research Center, Seoul National University, Seoul, Korea, Republic of, 2Department of Biomedical Software Engineering, The Catholic University of Korea, Bucheon, Korea, Republic of, 3Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of.
OBJECTIVES: Aromatase inhibitors (AIs), including anastrozole, letrozole, and exemestane, are cornerstone therapies for hormone receptor-positive breast cancer in postmenopausal as well as premenopausal women. Given evidence that metabolic factors can alter the risk profiles of therapies, this study investigates the impact of body weight on AI-related adverse drug reactions (ADRs) using real-world pharmacovigilance data.
METHODS: Suspected ADR reports from Q1 2004 to Q4 2023 were extracted using the FDA Adverse Event Reporting System (FAERS) database. Cases were categorized into overweight (n=1,849,356) and non-overweight (n=1,215,580) groups, based on a prespecified CDC-based weight cutoff. Disproportionality analyses were conducted separately for each group using reporting odds ratios (RORs) based on MedDRA preferred terms (PTs). For ADRs with statistically significant signals only in the overweight group, logistic regression was used to assess the interaction between body weight and AI exposure, estimating the relative ROR. Significance was defined as the lower bound of a 95% confidence interval (CI) of the relative ROR>1.
RESULTS: The analysis identified 163 PTs with signals unique to the overweight group; 12 PTs showed significantly stronger signals in the overweight group compared to the non-overweight group. These included metabolic-related events such as hypothyroidism (relative ROR: 2.49; 95% CI: 1.07-5.81), hypocalcaemia (3.99; 1.63-9.81), and hyperuricaemia (11.92; 1.48-95.78). Hematologic/neoplastic events such as granulocyte count decreased (11.94; 2.35-60.79) and lymphangiosis carcinomatosa (6.29; 1.12-35.40) also showed stronger signals in the overweight group. Other events involved the musculoskeletal system, including tenosynovitis stenosans (20.94; 2.67-164.25), muscle atrophy (5.25; 1.16-23.78), and pelvic fracture (8.70; 1.08-69.81); the dermatologic system, including toxic skin eruption (8.05; 1.00-64.59) and palmar-plantar erythrodysaesthesia syndrome (2.67; 1.10-6.46); and the neurologic/pulmonary systems, including ageusia (6.28; 1.47-26.82) and pneumothorax (15.18; 1.97-117.00).
CONCLUSIONS: This study highlights differences in AI-related ADR profiles based on patient body weight. Further research is needed to refine personalized treatment strategies and enhance risk stratification by patient characteristics.
METHODS: Suspected ADR reports from Q1 2004 to Q4 2023 were extracted using the FDA Adverse Event Reporting System (FAERS) database. Cases were categorized into overweight (n=1,849,356) and non-overweight (n=1,215,580) groups, based on a prespecified CDC-based weight cutoff. Disproportionality analyses were conducted separately for each group using reporting odds ratios (RORs) based on MedDRA preferred terms (PTs). For ADRs with statistically significant signals only in the overweight group, logistic regression was used to assess the interaction between body weight and AI exposure, estimating the relative ROR. Significance was defined as the lower bound of a 95% confidence interval (CI) of the relative ROR>1.
RESULTS: The analysis identified 163 PTs with signals unique to the overweight group; 12 PTs showed significantly stronger signals in the overweight group compared to the non-overweight group. These included metabolic-related events such as hypothyroidism (relative ROR: 2.49; 95% CI: 1.07-5.81), hypocalcaemia (3.99; 1.63-9.81), and hyperuricaemia (11.92; 1.48-95.78). Hematologic/neoplastic events such as granulocyte count decreased (11.94; 2.35-60.79) and lymphangiosis carcinomatosa (6.29; 1.12-35.40) also showed stronger signals in the overweight group. Other events involved the musculoskeletal system, including tenosynovitis stenosans (20.94; 2.67-164.25), muscle atrophy (5.25; 1.16-23.78), and pelvic fracture (8.70; 1.08-69.81); the dermatologic system, including toxic skin eruption (8.05; 1.00-64.59) and palmar-plantar erythrodysaesthesia syndrome (2.67; 1.10-6.46); and the neurologic/pulmonary systems, including ageusia (6.28; 1.47-26.82) and pneumothorax (15.18; 1.97-117.00).
CONCLUSIONS: This study highlights differences in AI-related ADR profiles based on patient body weight. Further research is needed to refine personalized treatment strategies and enhance risk stratification by patient characteristics.
Conference/Value in Health Info
2025-09, ISPOR Real-World Evidence Summit 2025, Tokyo, Japan
Value in Health Regional, Volume 49S (September 2025)
Code
RWD244
Topic Subcategory
Health & Insurance Records Systems
Disease
SDC: Oncology