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Hypersensitivity reactions with allopurinol and febuxostat: a study using the Medicare claims data
  1. Jasvinder A. Singh1,2,
  2. John D. Cleveland1
  1. 1 Departments of Medicine and Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA
  2. 2 Medicine Service, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, USA
  1. Correspondence to Dr Jasvinder A. Singh, University of Alabama at Birmingham, Birmingham, AL 35294, USA;{at}


Objective To assess the risk of hypersensitivity reactions (HSRs) with allopurinol and febuxostat in a population-based study.

Methods We used the 5% Medicare beneficiary sample (≥65 years) from 2006 to 2012 to identify people with a newly filled prescription for allopurinol, febuxostat or colchicine. We used multivariable-adjusted Cox regression analyses to compare the hazard ratio (HR) of incident HSRs with allopurinol or febuxostat use versus colchicine use; separate analyses were done in people exposed to allopurinol. Propensity-matched analyses (5:1) compared hazards with allopurinol versus febuxostat.

Results Crude incidence rates of HSRs were as follows: allopurinol, 23.7; febuxostat, 30.7; and colchicine, 25.6 per 1000 person-years. Compared with colchicine, allopurinol, febuxostat and febuxostat+colchicine were associated with significantly higher HRs of HSRs, 1.32 (95% CI: 1.10 to 1.60) and 1.54 (95% CI: 1.12 to 2.12) and 2.17 (95% CI: 1.18 to 3.99), respectively. In propensity-matched analyses, febuxostat did not significantly differ from allopurinol; HR for HSRs was 1.25 (95% CI: 0.93 to 1.67). Compared with allopurinol start dose <200 mg/day, allopurinol start dose ≥300 mg/day, diabetes and female sex were associated with significantly higher hazard of HSRs, 1.27 (95% CI: 1.12 to 1.44), 1.21 (95% CI: 1.00 to 1.45) and 1.32 (95% CI: 1.17 to 1.48), respectively. The majority (69%) of HSRs occurred in the outpatient setting.

Conclusions Compared with colchicine, allopurinol and febuxostat similarly increased the risk of HSRs. Allopurinol and febuxostat did not differ from each other. In allopurinol users, starting dose, female sex and diabetes increased this risk, findings that need further study.

  • gout
  • epidemiology
  • outcomes research

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  • Handling editor Josef S Smolen

  • Contributors JAS: designed the study, developed study protocol, reviewed analyses and wrote the first draft of the paper. JC: performed the data abstraction and data analyses. All authors revised the manuscript, read and approved the final manuscript.

  • Funding This material is the result of work supported by research funds from the Division of Rheumatology at the University of Alabama at Birmingham and the resources and use of facilities at the Birmingham VA Medical Center, Birmingham, Alabama, USA. The funding body did not play any role in design, in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication.

  • Competing interests JAS has received consultant fees from Crealta/Horizon, Medisys, Fidia, UBM LLC, Trio health, Medscape, WebMD, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, Practice Point communications, the National Institutes of Health and the American College of Rheumatology. JAS owns stock options in Amarin pharmaceuticals and Viking therapeutics. JAS is on the speaker’s bureau of Simply Speaking. JAS is a member of the executive of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from 12 companies. JAS serves on the FDA Arthritis Advisory Committee. JAS is the chair of the Veterans Affairs Rheumatology Field Advisory Committee. JAS is the editor and the Director of the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis. JAS previously served as a member of the following committees: member, the American College of Rheumatology’s (ACR) Annual Meeting Planning Committee (AMPC) and Quality of Care Committees, the Chair of the ACR Meet-the-Professor, Workshop and Study Group Subcommittee and the co-chair of the ACR Criteria and Response Criteria subcommittee.

  • Patient consent for publication Not required.

  • Ethics approval The University of Alabama at Birmingham’s Institutional Review Board approved this study and all investigations were conducted in conformity with ethical principles of research (X1201207004). The IRB waived the need for informed consent of patients for this database study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. Data may be obtained from a third party and are not publicly available. These data can be obtained from the Centers for Medicare and Medicaid Services (CMS) Chronic Condition Data Warehouse. The authors are ready to share the data with colleagues, after obtaining appropriate permissions from the Centers for Medicare and Medicaid Services (CMS) Chronic Condition Data Warehouse and the University of Alabama at Birmingham (UAB) Ethics Committee, related to HIPAA and Privacy policies.