Introduction
Gout, chronic kidney disease, cardiovascular disease, gout
INFLAMMATORY ARTHRITIS, GOUT, CARDIOVASCULAR DISEASE, GOUT
A 2016 meta-analysis revealed that 90% of compounds failed in phase 2/3 clinical trials, 30% due to safety concerns, reflecting high failure rate in the drug discovery process [Numerous strategies are commonly deployed in drug development for de-risking pre-clinical molecules. In this study, we sought to test the utility of a human drug-response database for understanding cardiovascular safety of front-line gout medications. These medications have a well-developed clinical profile, yet recent clinical trial data appears to contradict United States Food and Drug Administration (FDA) warnings of cardiovascular risk.Gout is the most common inflammatory arthritis, and the frequent presence of specific comorbidities, including cardiovascular disease and chronic kidney disease increase the mortality rate. In addition to anti-inflammatory therapies for flares, gout is primarily managed with the xanthine oxidase inhibitors febuxostat or allopurinol to lower serum urate levels. Febuxostat is widely prescribed as a second-line therapy where allopurinol is ineffective, not tolerated, or contraindicated [