Varying frequencies of HLA-B*5801 carriage across different races and ethnic groups could lead to major disparities in SJS/TEN risk and adverse events among patients who take allopurinol, the researchers warn. The study tested Dr. Choi’s hypothesis that having information on racial and ethnic descent—even before genotyping—could enhance risk stratification to prevent serious adverse events among gout patients. “We wanted to use race and ethnicity as obvious information that could be used to help prevent allopurinol hypersensitivity syndrome,” he explains.
To test their hypothesis, the researchers analyzed data from the Nationwide Inpatient Sample (NIS), a nationally representative, all-payer inpatient care database maintained by the Agency for Healthcare Research and Quality, representing between five and eight million hospital discharges annually. For reference data, researchers included statistics from the U.S. Census population and the National Health and Nutrition Examination Survey (NHANES) for 2009–2012.
Results
The researchers’ analysis of NIS data from between 2009 and 2013 identified 606 hospitalizations of patients with both a principal diagnosis of SJS/TEN and a secondary diagnosis of an adverse event caused by a ULD. Although the database did not identify specific drugs, the researchers assumed that most, if not all, of the adverse reactions involved allopurinol because it is prescribed so frequently.
Meanwhile, the researchers’ NHANES data analysis showed that allopurinol constituted 97% of ULD use.
Asian and black patients hospitalized with SJS/TEN in combination with a secondary diagnosis of an adverse event caused by a ULD were significantly over-represented, compared with Caucasians. The NIS data show that patients with these diagnoses were 27% Asian American, 26% African American and 29% Caucasian. However, Asian Americans, African Americans and Caucasians make up 5%, 12% and 67% of the U.S. population, the researchers note.
Although Hispanics are the largest minority race according to U.S. Census data, the number of SJS/TEN cases among the group was too small to report. The frequency of SJS/TEN cases among Hispanics is unlikely to be higher than any other race, the researchers write.
According to the NHANES data, black patients represented 13% of allopurinol users, and NIS figures show that blacks represented 26% of all hospitalizations for of SJS/TEN in combination with a secondary diagnosis of an adverse event caused by a ULD. Asian patients represented only 2% of U.S. allopurinol users in 2011–12, but 27% of those hospitalized for SJS/TEN related to ULDs. Caucasian patients represented 81% of allopurinol users, but only 29% of hospitalizations. Very few Hispanic patients with these diagnoses were included in the hospitalization database, the researchers note.
These ‘findings apply almost exclusively to patients who are starting allopurinol, since nearly all of these severe adverse events occur during the first three to six months of treatment.’ —Dr. Choi
Clinical Implications
The paper’s findings support the ACR recommendation to screen for HLA-B*5801 carriage in high-risk Asian groups and suggest doing so for blacks, “particularly when there are co-existing risk factors, such as chronic kidney disease,” says Dr. Choi.
