Febuxostat Hypersensitivity Risk in Gout Similar to Allopurinol

Febuxostat and allopurinol are effective uric acid-lowering treatments for gout, but both can cause adverse reactions, in particular, allopurinol, which is associated with hypersensitivity reactions such as fever, cutaneous reactions, eosinophilia, hepatic abnormalities, and acute renal failure.

Less is known about the degree of hypersensitivity reactions associated with febuxostat (Uloric, Takeda) use, but in a new study published in the February 5 issue of Annals of the Rheumatic Diseases, Dr. Jasvinder A. Singh of the University of Alabama, and colleagues, report that allopurinol and febuxostat are associated with about the same risk of hypersensitivity reactions, as compared to gout patients treated with colchicine (Colcrys, Takeda). The risk is even higher for women and diabetes patients, the authors wrote.

Hypersensitivity reactions are uncommon, but well documented in patients treated with allopurinol (Zyloprim, Mylan). Female sex, older age, renal or cardiovascular comorbidities, and a higher allopurinol start have been shown in previous studies as risk factors for allopurinol hypersensitivity reactions.

The new study is based on a review of Medicare cases from 2006 to 2012. Of 39,261 cases and 66,178 new prescriptions for colchicine, allopurinol, febuxostat, 1,038 hypersensitivity reactions occurred. Hypersensitivity reactions occurred in 23.7, 25.6, and 30.7, per 1,000 person-years for allopurinol, colchicine, and febuxostat. Medication combinations, particularly febuxostat plus colchicine, or a combination of all three drugs, resulted in a reaction rate of 56.8 and 89.1 per 1,000 person-years, respectively.

Compared with colchicine, allopurinol, febuxostat, and febuxostat plus colchicine was associated with significantly higher hazard ratios (HR) of hypersensitivity reactions, 1.32,  1.54 , and 2.17, respectively.  Meanwhile, febuxostat did not significantly differ from allopurinol, HR of hypersensitivity reactions was 1.25, in propensity-matched analyses.

Compared with an allopurinol start dose below 200 mg per day, an allopurinol start dose of at least 30 mg per day was associated with significantly higher HR of hypersensitivity reactions (1.27),  as was diabetes (1.21) and female sex (1.32), but not renal failure. Of hypersensitivity reactions, 69 percent occurred in the outpatient setting.

Future study is required to analyze why a higher allopurinol start dose, diabetes and female sex increased the risk of hypersensitivity reactions in allopurinol users, the authors wrote.

REFERENCE

Jasvinder A. Singh, John D. Cleveland. “Hypersensitivity reactions with allopurinol and febuxostat: a study using the Medicare claims data.”Annals of the Rheumatic Diseases. February 05, 2020. doi: 10.1136/annrheumdis-2019-216917