Risk factors for zolbetuximab-associated nausea and vomiting: a pharmacovigilance analysis using the Japanese Adverse Drug Event Report (JADER) database

Zolbetuximab, a monoclonal antibody against claudin-18.2 (CLDN18.2), improves outcomes in CLDN18.2-positive gastric cancer, but gastrointestinal adverse events—especially nausea and vomiting—are frequently reported. Using PMDA-JADER (April 2004–March 2025), we identified individual case safety reports (ICSRs) listing zolbetuximab as a suspected drug and defined the outcome with MedDRA-concordant preferred terms (nausea, vomiting, nausea and vomiting, retching). Within zolbetuximab reports, binary logistic regression with sex (male reference) and age (<60 years reference) showed higher adjusted odds in females (aOR 3.07; 95% CI 1.45–6.51; p=0.003) and lower odds in patients ≥60 years (aOR 0.25; 95% CI 0.10–0.61; p=0.002); model calibration was acceptable (Hosmer–Lemeshow p=1.000). Disproportionality analysis yielded a markedly elevated reporting odds ratio (ROR) for zolbetuximab versus all other reports (ROR 85.40; 95% CI 62.58–116.53), whereas immune checkpoint inhibitors showed no signal. These measures reflect reporting disproportionality within a spontaneous-reporting system and should not be interpreted as incidence or causality. These exploratory findings support proactive, guideline-based antiemetic strategies—particularly for younger female patients—and warrant prospective confirmation.