Allopurinol, Febuxostat Carry Similar Risks for Hypersensitivity Reactions
Both allopurinol and febuxostat carry similar, significant increased risks for hypersensitivity reactions compared with colchicine, according to data published in Annals of the Rheumatic Diseases.
“There are many gaps in our knowledge regarding the rare hypersensitivity drug reactions with allopurinol vs. other alternative medications used for the treatment of gout,” Jasvinder A. Singh, MD, MPH, of the University of Alabama at Birmingham, told Healio Rheumatology. “While every patient and physician fears the allopurinol hypersensitivity syndrome, also called AHS, which is a rarely-occurring major drug reaction with allopurinol, our study examined all hypersensitivity drug reactions, major or minor, with allopurinol vs. other drugs in the elderly.”
“Very few published studies and data are available that provide any population-level comparative data of the risk of hypersensitivity reactions associated with allopurinol and febuxostat,” he added. “Our study attempted to fill this knowledge gap, using data from the U.S. Medicare.”
Singh and colleagues studied the 5% random sample of Medicare beneficiaries from 2006 to 2012, obtained from CMS. The researchers used both this summary and the Medicare Part D file to identify beneficiaries enrolled in Medicare fee-for-service with pharmacy coverage and not in a Medicare Advantage Plan, who lived in the United States during the study period and filled a new prescription for allopurinol, febuxostat or colchicine.
Singh and colleagues identified 39,261 individuals with 66,178 new episodes of allopurinol, febuxostat or colchicine use. The researchers used multivariable-adjusted Cox regression analyses to compare the HR of incident hypersensitivity reactions associated with allopurinol or febuxostat, compared with colchicine. In addition, they used propensity-matched analyses to compare hazards associated with allopurinol and febuxostat.
According to the researchers, the crude incidence rates for hypersensitivity reactions were 23.7 per 1,000 person-years for allopurinol, 30.7 for febuxostat and 25.6 with colchicine. Compared with colchicine, allopurinol (HR = 1.32; 95% CI, 1.1-1.6), febuxostat (HR = 1.54; 95% CI, 1.12-2.12) and febuxostat along with colchicine (HR = 2.17; 95% CI, 1.18-3.99) were associated with significantly higher risks for hypersensitivity reactions. In addition, following propensity-matched analyses, febuxostat did not significantly differ from allopurinol.
Compared with an allopurinol starting dose of less than 200mg per day, an allopurinol starting dose of 300mg or more per day (HR = 1.27; 95% CI, 1.12-1.44), diabetes (HR = 1.21; 95% CI, 1-1.45) and female sex (HR = 1.32; 95% CI, 1.17-1.48) were associated with significantly higher risks for hypersensitivity reactions. Approximately 69% of hypersensitivity reactions occurred in an outpatient setting.
“Our study provides crude incidence rates of hypersensitivity reactions in adults 65 years or older, exposed to allopurinol, febuxostat, colchicine or their combinations,” Singh said. “Our study shows that the two most commonly used urate-lowering therapies, allopurinol and febuxostat, are associated with a similar hazard of hypersensitivity reactions.” – by Jason Laday
Disclosure: Singh reports consultant fees from the American College of Rheumatology, Clearview Healthcare Partners, Clinical Care Options, Crealta/Horizon, Fidia, Focus Forward, Medisys, Medscape, Navigant Consulting, the NIH, Practice Point Communications, Putnam Associates, Spherix, Trio Health, UBM and WebMD; stock options in Amarin pharmaceuticals and Viking therapeutics; and speaking fees from Simply Speaking.