Insights from pharmacovigilance databases, clinical cohorts and preclinical models into VEGF(R) inhibitor-induced arthritis in cancer.

BACKGROUND: VEGF and VEGFR inhibitors are key in targeted therapy for various malignancies, but arthritis-related side effects are poorly understood. This study investigates the incidence, risk factors, and molecular mechanisms of VEGF(R) inhibitor-induced arthritis. METHODS: Statistical analyses of VEGF(R) inhibitor-related arthritis adverse events were conducted using data from the Food and Drug Administration Adverse Event Reporting System (FAERS) and the World Health Organization's global individual case safety reports database (VigiBase), with risk assessment performed using reporting odds ratio (ROR) and proportional reporting ratio (PRR). The effects of VEGF(R)i treatment on arthritis-related biomarkers were validated through the analysis of clinical data from cancer patients receiving VEGF(R)i therapy. A VEGF(R)i-treated mouse model was established using only male mice to investigate transcriptomic changes in bone tissue using high-throughput sequencing technology, thereby exploring potential mechanisms of VEGF(R)i-related arthritis. RESULTS: FAERS and VigiBase data show a significant link between VEGF(R) inhibitors and arthritis, with a higher incidence in females and individuals under 65. Clinical data reveal elevated inflammatory markers post-treatment. Transcriptomic analysis shows the activation of some and suppression of other inflammation-related pathways in bone tissue after VEGF(R) inhibitor treatment. CONCLUSIONS: This study provides a systematic analysis of VEGF(R) inhibitor-related arthritis, reveals its incidence patterns and potential molecular mechanisms, and offers insights into prevention and treatment strategies for this side effect in clinical practice.