Effect of febuxostat on adverse events and mortality in gout in Taiwan: An interrupted time series analysis

Objectives: To evaluate the influence of febuxostat on adverse events and mortality in gout. Methods: We retrospectively enrolled patients with newly diagnosed gout and prescribed urate-lowering therapy between 2006 and 2017 from the Taiwan National Health Insurance Database. These patients were divided into 2 groups: with and without comorbidities (n = 294 847 and 194 539). An interrupted time series analysis with adjustments for demographics, comorbidities, and comedication by propensity score-based stabilized weights was used to compare the trend of adverse events and mortality before vs after febuxostat was introduced in 2012. Results: The proportion of febuxostat use gradually increased from 0% in 2012 to 30% in those with comorbidities and 10% in those without comorbidities in 2017. Allopurinol use decreased from 30% in 2012 to 10% in 2017. The slope of the 1-year incidence rate of Stevens–Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) (per 10 000 patients) significantly reduced after 2012 in those with and without comorbidities (−0.375 per quarter, P =.015 and −.253 per quarter, P =.049). The slope of the 3-year incidence rate of acute myocardial infarction (AMI) (per 1000 patients), percutaneous coronary intervention (PCI) (per 1000 patients), and all-cause mortality (per 100 patients) significantly increased after 2012 in those with comorbidities (+0.207 per quarter, P =.013; +.389 per quarter, P =.002; +.103 per quarter, P =.001). Conclusions: Febuxostat may reduce SJS and TEN in all gout patients but increase AMI, PCI, and all-cause mortality in gout patients with comorbidities.