Gene Variant Explains Racial Disparities in Adverse Reactions to Urate-Lowering Drug

A multi-institutional study led by a Massachusetts General Hospital (MGH) investigator finds significant racial disparities in the risk that patients being treated for gout will develop a serious, sometimes life-threatening adverse reaction to the most commonly prescribed medication. The increased risk closely correlates with the frequency of a gene variant previously associated with that adverse reaction, supporting recommendations to screen for that variant in patients from those populations.

“We found that Asian and black patients have a substantially higher risk of severe cutaneous adverse reactions to urate-lowering drugs than do white or Hispanic patients, which correlates with the frequency of the HLA-B*5801 gene in their U.S. populations,” says Hyon K. Choi, MD, DrPH, of the MGH Division of Rheumatology, Allergy and Immunology, senior author of the report that has been published online in Seminars in Arthritis and Rheumatism. “This risk is almost certainly due to allopurinol, the dominant urate-lowering drug in the U.S., and screening gout patients from those populations for the HLA-B*5801 variant could help increase treatment safety.”

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Severe cutaneous reactions to allopurinol–which are called toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS)–are rare, but can be extremely serious. In TEN, overwhelming inflammation causes the outer layer of skin to separate from the underlying layers, leaving the body open to severe infections. SJS/TEN can be fatal more than 30 percent of the time and may involve other major organs, potentially leaving survivors with long-term damage to the kidneys or eyes.

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From that database of between 5 and 8 million hospitalizations each year, they identified 606 with a principal diagnosis of SJS/TEN related to an adverse reaction to urate-lowering drugs. {snip}

Among patients with that diagnosis [of SJS/TEN], there was a significant over-representation of Asian and black patients compared with whites. For example, while another database indicates that Asian patients represented only 2 percent of U.S. allopurinol users in 2011-12, they represented 27 percent of those hospitalized for SJS/TEN related to urate-lowering drugs. Black patients represented 13 percent of allopurinol users and 26 percent of hospitalizations, while white patients represented 81 percent of allopurinol users but only 29 percent of hospitalizations. The number of Hispanic patients in the hospitalization database with this diagnosis was extremely small.

Overall the risk of these dangerous reactions was 12 times higher for Asian patients and 5 times higher for black patients compared with white patients. Those differences are closely aligned with the frequency of the HLA-B*5801 variant in those populations–a 7.4 percent frequency in Asians, 4 percent in blacks, and 1 percent in both whites and Hispanics.

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