Allopurinol, Febuxostat Carry Similar Risks for Hypersensitivity Reactions
Click Here to Manage Email Alerts
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.
Perspective
Back to Top
David A. McLain, MD, FACP, FACR
In a clinical study, certain clinical and laboratory characteristics are described that are part of a diagnostic criteria. For example, a study of allopurinol hypersensitivity would require the presence of either two of the major criteria (worsening renal function, acute hepatocellular injury or rash) or one of the major criteria and one of the minor criteria (fever, eosinophilia or leukocytosis). However, in a database study, like the one Singh and colleagues have conducted, the researchers have to select diagnostic codes and hope that the combination is defining an accurate clinical picture of, in this case, hypersensitivity reactions.
In this study, the authors used a validated algorithm that defines hypersensitivity reactions based on ICD-9 codes; Singh and colleagues noted that the use of codes can lead to misclassification or under documentation or overdocumentation of hypersensitivity reactions.
Their findings indicate that the febuxostat hypersensitivity reaction rate in the Medicare population exceeds the allopurinol rate. They also found a higher hypersensitivity reaction rate in those who started on higher initial allopurinol doses as well as those with diabetes, possibly due to renal disease.
Combination therapy — allopurinol or febuxostat with colchicine or all three together — had the highest incidences of hypersensitivity reactions. This study is of interest due to the large size of the database as well as providing a retrospective review of reaction rates to the three main gout medications .
Collapse
Read more about
Click Here to Manage Email Alerts