Use of febuxostat (Uloric) decreased among patients with gout in the United States following a Food and Drug Administration–mandated black-box warning that cited cardiovascular concerns, but overall use of urate-lowering therapy remained stable, according to data from a study of commercial insurance enrollees in the United States between 2009 and 2019.
Initiation of urate-lowering therapy (ULT) is recommended for gout patients, and allopurinol remains the first-line treatment, but it is not effective in all patients, and febuxostat was developed as an alternative, wrote, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues.
However, based on data from a postmarketing safety trial (the CARES trial) mandated by the FDA, the agency first issued a safety announcement about an increased risk of cardiovascular mortality with febuxostat in November 2017, followed in February 2019 with a black-box warning after full CARES trial results were published in March 2018 showing a greater risk of cardiovascular and all-cause mortality in febuxostat versus allopurinol.
In a study published in, the researchers examined trends in the use of ULT before and after the FDA warning. They analyzed claims data from a national commercial health database that included 838,432 adult ULT users and 633,229 gout patients.
Overall, allopurinol accounted for the majority of ULT use between 2009 (95% in the first quarter) and 2019 (92% in the fourth quarter).
Febuxostat use peaked at 10% of all ULT use in 2013 and 2014, after a gradual increase following its introduction into the market in 2009, the researchers noted, but decreased to 6% of all ULT use in the fourth quarter of 2019. Other medications, including probenecid, lesinurad (Zurampic), and pegloticase (Krystexxa), accounted for no more than 5% of ULT use.
When the researchers examined gout patients in particular, they found a slight increase in any ULT use from 567 per 1,000 patients in the first quarter of 2009 to 656 per 1,000 patients in the fourth quarter of 2019.
The study findings were limited by several factors, including potential lack of generalizability to other health plans and lack of adjustment for comorbid conditions, the researchers noted.
However, the results highlight the suboptimal use of ULT as a class and the need to address the treatment gap in gout patients “with appropriate ULT prescribing and monitoring,” they said. “While the decrease in febuxostat use was accompanied by a compensatory increase in allopurinol use, the proportion of patients with gout without any ULT remained high throughout the study period,” they concluded.
The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Dr. Kim disclosed receiving research grants to Brigham and Women’s Hospital from Pfizer, AbbVie, Roche, and Bristol-Myers Squibb for research unrelated to the current study.
SOURCE: Kim SC et al. Arthritis Rheumatol. 2020 Oct 7.