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

Published on: 

Leveraging data from a pair of commercial databases, a new study details the changes in febuxostat prescribing among patients with gout before, during, and after the FDA's addition of a Boxed Warning to prescribing information.

A new study is providing clinicians with a breakdown of the impact of 2019 label changes on real-world febuxostat (Uloric) following the US Food and Drug Administration (FDA)’s addition of a Boxed Warning to the packaging for the gout treatment.

An analysis of data from the IQVIA PharMetrics Plus database and the Optum Research Database, results of the study detail a decline in the real-world utilization of febuxostat following the FDA’s issuance of a drug safety communication in 2017 and lasting through the duration of the study period.1

“The results of this study do not change the benefit–risk profile of febuxostat. Across the three study periods, both the number of new users and prevalent new users decreased, presumably due to the label change. The proportion of patients initiating febuxostat as new users also decreased over the course of the study period,” investigators wrote.1

Approved for the treatment of gout in 2009, Takeda Pharmaceuticals’ febuxostat became a staple in treatment algorithms for many with gout. As part of this approval, the FDA required the company to launch a safety trial assessing the long-term effects of use. In November 2017, the FDA alerted the public of preliminary study results from a safety trial indicating use of febuxostat was associated with an increased risk of heart-related death and death from all causes, which led to the issuance of a Boxed Warning in 2019.2,3

The current study was launched with the intent of exploring how the addition of this Boxed Warning impacted real-world use of febuxostat in patients with gout. To do so, investigators designed their study as a descriptive, nonintervention, cross-sectional study of the IQVIA PharMetrics Plus database and the Optum Research Database. The specific aim of the study was to describe the number of patients initiating new users or prevalent new users and data on febuxostat users with established cardiovascular disease morbidities before, during, and after the 2019 label changes.1

With this in mind, investigators designed their study to assess 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’s drug safety communication, the period between the FDA’s drug safety communication until the change in prescribing information, and the post-label change period.1

During the aforementioned periods, investigators sought to describe the numbers the number and proportions of patients initiating febuxostat as new users or prevalent users as well as the number of users with established cardiovascular disease morbidities before, during, and after the 2019 label changes.1

Upon analysis, results suggested the total number of febuxostat users and proportions of users who initiated febuxostat as new users decreased during 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 prevalent new users.1

Further analysis indicated the most commonly reported cardiovascular disease morbidities 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). Investigators pointed out there was a greater proportion of new users with preexisting heart failure/cardiomyopathy in the post-labeling change period (14.2% in PharMetrics Plus, 32.9% in Optum) compared to the baseline period (10.4% in PharMetrics Plus, 26.0% in Optum).1

“In addition to the FDA communications regarding [cardiovascular] safety, the decrease 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 of new prescriptions and refills) during the post-labeling change period,” investigators wrote.1


  1. Sosinsky AZ, Song Y, Gunawardhana L, Phillips S, Page M. The Impact of Label Changes (Boxed Warning) on Real-World Febuxostat Utilization in Patients with Gout: A Cross-Sectional Drug Utilization Study [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. Heart-related death and death from Gout Medicine Febuxostat (uloric). U.S. 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. U.S. Food and Drug Administration. February 21, 2019. Accessed July 22, 2023.