1. Between 2005 and 2011, the percentage of patients from the Taiwanese National Health Insurance database who received allopurinol for asymptomatic hyperuricemia increased significantly. In the same time period, the rate of hypersensitivity conditions attributed to allopurinol also increased significantly.
2. In patients with renal or cardiovascular comorbidities, allopurinol use for asymptomatic hyperuricemia was associated with statistically significant increased risk of hypersensitivity reactions and mortality.
Evidence Rating Level: 2 (Good)
Study Rundown: Allopurinol has been a mainstay of treatment for gouty arthropathy, uric acid nephrolithiasis, and hyperuricemia secondary to cancer or chemotherapy. However, this medication is not without adverse effects, and is associated with hypersensitivity syndromes including, but not limited to, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Allopurinol is often used in asymptomatic hyperuricemia in patients with renal and cardiovascular comorbidities, as it is thought that high serum uric acid can exacerbate these conditions. This study studied the association of hypersensitivity reactions with allopurinol for asymptomatic hyperuricemia.
This study found that in patients with renal or cardiovascular comorbidities, allopurinol use for asymptomatic hyperuricemia was associated with increased risk of hypersensitivity reactions and mortality. Additional risk factors identified for allopurinol related hypersensitivity reactions included female sex, age greater than 60 years, and allopurinol dose greater than 100 mg/day. Strengths of the study include the large number of patients analyzed. However, the population studied was ethnically homogenous (98% Han Chinese), which may limit its generalizability. Moreover, the results were based on insurance claims data and diagnosis codes, which did not reflect the severity of the hypersensitivity reactions.
Click to read the study, published today in JAMA Internal Medicine
Relevant Reading: Allopurinol Hypersensitivity: A Systematic Review of All Published Cases, 1950–2012
In-Depth [retrospective cohort]: This retrospective cohort study examined data collected from the Taiwan National Health Insurance Research database, gathered from 2005 to 2011. The study identified new users of allopurinol, which was defined as receiving the medication in the past 3 years. ICD-9 codes were identified for hypersensitivity conditions, including dermatitis due to medicines, erythema multiforme, SJS, TEN, and unspecified erythematous conditions, occurring in the first 3 months of receiving allopurinol.
A total of 1 613 719 patients receiving allopurinol prescriptions were identified. During the study period, the percentage of patients receiving allopurinol for asymptomatic hyperuricemia increased from 36.7% to 49.5%, and the incidence of hypersensitivity reactions increased from 3.71 per 1000 new users to 6.12 per 1000 new users (p < 0.001). Comorbid chronic renal disease and comorbid cardiovascular disease were associated with increased risk of hypersensitivity (OR 1.49, 95%CI 1.38-1.61 and OR 1.13, 95%CI 1.04-1.22, respectively), and increased risk of mortality (OR 2.20 and OR 1.79, respectively). These associations remained significant when analyzed for patients receiving allopurinol for asymptomatic hyperuricemia.
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