Study Details Decline in Febuxostat Use Following Addition of Boxed Warning by FDA

A new study is providing clinicians with a breakdown of the real-world impact of the 2019 labeling changes to febuxostat (Uloric) following the U.S. Food and Drug Administration (FDA)’s addition of a boxed warning to packaging for the treatment of gout.

An analysis of data from the IQVIA PharMetrics Plus database and the Optum Research Database, study results detail a decline in actual febuxostat usage following the FDA’s issuance of a drug safety communication in 2017 and throughout the study period.1

The results of this study do not change the benefit-risk profile of febuxostat. During the three study periods, both the number of new users and new prevalent users decreased, presumably due to the label switch. The proportion of patients who started febuxostat treatment as new users also decreased over the study period, the researchers wrote.1

Approved to treat gout in 2009, Takeda Pharmaceuticals’ febuxostat has become a staple in treatment algorithms for many with gout. As part of this approval, the FDA has required the company to initiate a safety trial to evaluate the long-term effects of use. In November 2017, the FDA alerted the public to the results of a preliminary study of a safety study that indicated that the use of febuxostat was associated with an increased risk of death from cardiac causes and death from all causes, leading to the issuance of a Boxed Warning in 2019.2.3

The current study was initiated with the intent to explore how the addition of this Boxed Warning affected the actual use of febuxostat in patients with gout. To do so, the researchers designed their study as a descriptive, non-interventional, cross-sectional study of the IQVIA PharMetrics Plus database and the Optum Research Database. The specific purpose of the study was to describe the number of patients who initiated new users or new prevalent users and data on febuxostat users with established cardiovascular disease before, during, and after the 2019 labeling changes.1

With this in mind, the researchers designed their study to assess the change in prescribing trends during 3 periods of interest, which were June 1, 2016-November 15, 2017, November 16, 2017-February 21, 2019, and February 22, 2019-June 30, 2020. These time periods reflect the 18 months prior to the FDA drug safety communication, the period between the FDA drug safety communication until the prescription and post-label modification period.1

During these periods, the researchers sought to describe the numbers, number and proportions of patients who started treatment with febuxostat as new users or heavy users, as well as the number of users with established cardiovascular disease before, during and after the 2019 labeling changes.1

After analysis, the results suggested the total number of febuxostat users and the proportions of users initiating febuxostat treatment while new users decreased over the study period in both databases. A total of 13,848 patients were identified within the IQVIA PharMetric Plus cohort. Of these, 42.7% were new users and 57.3% were prevalent new users. A total of 10,198 patients were identified within the Optum Research Database. Of these, 40.5% were new users and 59.5% were new prevalent users.1

Additional analyzes indicated that the most commonly reported cardiovascular disorders in the 12 months prior to initiation of febuxostat were diabetes mellitus (28% in PharMetrics Plus, 47% in Optum), ischemic heart disease (17% in PharMetrics Plus, 33% in Optum), and heart failure/cardiomyopathy (13% in PharMetrics Plus, 28% in Optum). The investigators noted that there was a higher proportion of new users with pre-existing heart failure/cardiomyopathy in the post-labeling change period (14.2% in PharMetrics Plus, 32.9% in Optum) than in the baseline period (10.4% in PharMetrics Plus, 26.0% in Optum).1

In addition to FDA communications regarding [cardiovascular] safety, the decline in the number of new and prevalent new users of febuxostat in this study may be partially explained by the impact of COVID-19, which limited access to healthcare resources (including writing new prescriptions and refills) during the post-labelling change period, the researchers wrote.1


  1. Sosinsky AZ, Song Y, Gunawardhana L, Phillips S, Page M. The impact of label changes (boxed warning) on ​​real-world febuxostat usage in patients with gout: a cross-sectional study of drug utilization [published online ahead of print, 2023 Jul 17].Rheumatol Ther. 2023;10.1007/s40744-023-00581-x. doi:10.1007/s40744-023-00581-x
  2. Center for Drug Evaluation and Research. Cardiac death and death from gout Medicine Febuxostat (uloric). United States Food and Drug Administration. November 15, 2017. Accessed July 22, 2023.
  3. Center for Drug Evaluation and Research. FDA adds boxed warning for increased risk of death with gout medicine. United States Food and Drug Administration. February 21, 2019. Accessed July 22, 2023.

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