Ther Adv Drug Saf. 2025 Dec 18;16:20420986251406106. doi: 10.1177/20420986251406106. eCollection 2025.
ABSTRACT
BACKGROUND: Baricitinib is widely used for immune-mediated diseases, yet real-world safety in underrepresented age groups and the temporal dynamics of adverse drug reactions (ADRs) remain insufficiently characterized.
OBJECTIVE: To identify age-stratified ADR signals of baricitinib and to examine potential causal roles of Janus kinase (JAK) 1/2 inhibition in key ADRs.
DESIGN: A retrospective pharmacovigilance study integrating disproportionality analysis, Mendelian randomization (MR), and time-to-onset (TTO) assessment.
METHODS: Baricitinib-associated ADRs reported to the FDA Adverse Event Reporting System (FAERS; Q3-2018 to Q1-2024) were analyzed using Reporting Odds Ratio and Bayesian Confidence Propagation Neural Network, stratified by age (18-65 vs ≥66 years). TTO was modeled to characterize temporal patterns. Two-sample MR using eQTL-based instruments of JAK1/2 expression evaluated causal links with thrombosis and atrial fibrillation (AF).
RESULTS: Among 5354 reports, infections were most frequent (28.3%). Thrombotic events (deep vein thrombosis, pulmonary embolism) were more prominent in the elderly (≥66 years), whereas hepatic enzyme elevation and malignancies were more frequent in adults aged 18-65 years. MR suggested that higher JAK2 expression was protective against thrombosis (OR = 0.998, p = 0.028), whereas higher JAK1 expression conferred increased risk of AF (OR = 1.255, p = 0.043). TTO analysis showed that thrombotic ADRs tended to occur early after baricitinib initiation, whereas certain malignancies emerged later.
CONCLUSION: This study highlights distinct age-dependent vulnerabilities to baricitinib-associated ADRs, with genetic evidence suggesting target-specific mechanisms underlying cardiovascular risk. These findings underscore the importance of age-tailored monitoring strategies and proactive pharmacovigilance in clinical practice.
PMID:41426305 | PMC:PMC12717373 | DOI:10.1177/20420986251406106