Risk factors for drug-related cachexia: an analysis based on the FDA adverse event reporting system (FAERS) from 2004...

Cachexia is a devastating metabolic syndrome that has a profound impact on survival rate and quality of life. Currently, there is still a scarcity of systematic evidence regarding drug-induced cachexia. This study aims to identify drugs associated with cachexia through the first large-scale pharmacovigilance analysis, and to characterize their risk features using real-world data.

Data from the U.S. FDA Adverse Event Reporting System (FAERS) from January 2004 and March 2025 were analyzed. Reports listing cachexia as an adverse event were extracted. Disproportionality analysis was performed on the top 50 most frequently reported drugs using reporting odds ratio (ROR), proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Multi-item Gamma Poisson Shrinker. A drug was considered a positive signal only if it met the threshold across all four methods. The Weibull shape parameter test was used to analyze the time-to-onset (TTO) profile.

Among 4,878 individual case safety reports of drug-related cachexia, the mortality rate was 25.6%. Disproportionality analysis identified 25 drugs with consistent positive signals across all four algorithms. These drugs spanned nine categories, with antineoplastic and immunomodulating agents being the most common. The drugs with stronger signals were low calcium peritoneal dialysis solution lactate G15 (ROR 495.67, 95% CI 336.94-729.18), Kaletra (ROR 10.44, 95% CI 7.98-13.65), and nivolumab (ROR 15.29, 95% CI 13.65-17.13). The drugs with a higher number of reported cases were nivolumab (319 cases), paclitaxel (160 cases), and Zometa (131 cases). The median TTO was 31 days, and more than half of cases occurred within the first 120 days, presenting an "early failure" pattern.

This study identified 25 drug safety warning signals that are significantly associated with the occurrence of cachexia. Cachexia is more likely to occur in the initial stage of drug treatment and has a high mortality rate. Continuous regulatory review and label updates of the safety information of relevant medications should be promoted.