Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study
نویسندگان
چکیده
OBJECTIVE To evaluate the use of prospective screening for the HLA-B*58:01 allele to identify Taiwanese individuals at risk of severe cutaneous adverse reactions (SCARs) induced by allopurinol treatment. DESIGN National prospective cohort study. SETTING 15 medical centres in different regions of Taiwan, from July 2009 to August 2014. PARTICIPANTS 2926 people who had an indication for allopurinol treatment but had not taken allopurinol previously. Participants were excluded if they had undergone a bone marrow transplant, were not of Han Chinese descent, and had a history of allopurinol induced hypersensitivity. DNA purified from 2910 participants' peripheral blood was used to assess the presence of HLA-B*58:01. MAIN OUTCOME MEASURES Incidence of allopurinol induced SCARs with and without screening. RESULTS Participants who tested positive for HLA-B*58:01 (19.6%, n=571) were advised to avoid allopurinol, and were referred to an alternate drug treatment or advised to continue with their prestudy treatment. Participants who tested negative (80.4%, n=2339) were given allopurinol. Participants were interviewed once a week for two months to monitor symptoms. The historical incidence of allopurinol induced SCARs, estimated by the National Health Insurance research database of Taiwan, was used for comparison. Mild, transient rash without blisters developed in 97 (3%) participants during follow-up. None of the participants was admitted to hospital owing to adverse drug reactions. SCARs did not develop in any of the participants receiving allopurinol who screened negative for HLA-B*58:01. By contrast, seven cases of SCARs were expected, based on the estimated historical incidence of allopurinol induced SCARs nationwide (0.30% per year, 95% confidence interval 0.28% to 0.31%; P=0.0026; two side one sample binomial test). CONCLUSIONS Prospective screening of the HLA-B*58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres.
منابع مشابه
A prospective study of HLA*B-5801 genotyping in preventing allopurinol- induced severe cutaneous adverse reactions
Background Allopurinol, a commonly prescribed medication for gout and hyperuricemia, is a frequent cause of severe cutaneous adverse reactions (SCAR), which include the hypersensitivity syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Allopurinol-induced SCAR is strongly associated with the HLA-B*58:01 allele. We sought to prevent allopurinol-induced SCAR by using HLA-B*58:01...
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OBJECTIVE Patients with an HLA-B*58:01 allele have an increased risk of developing severe cutaneous adverse drug reactions (SCAR) when treated with allopurinol. Although one-off pharmacogenetic testing may prevent life-threatening adverse drug reactions, testing prior to allopurinol initiation incurs additional costs. The study objective was to evaluate the cost-effectiveness of HLA-B*58:01 scr...
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The HLA B*58:01 allele has been worldwide reported as a pharmacogenetic susceptibility to allopurinol-induced severe cutaneous adverse reactions (SCARs). To prevent these life-threatening conditions, the American College of Rheumatology hingly recommended that the HLA-B*58:01 be screened prior to the initiation of allopurinol therapy. Therefore, we developed a rapid, robust, inexpensive screeni...
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Background Allopurinol has been reported as the most frequent causes of SCARs (severe cutaneous adverse reactions) in Thailand. Recent publications have shown that HLAB*58:01 allele is a strong marker for allopurinol-induced SJS/TEN (Stevens-Johnson syndrome/toxic epidermal necrolysis). The aim of this study was to clarify the association of allopurinol-induced SCARs with the HLA-B*58:01 allele...
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Severe cutaneous adverse drug reactions (SCARs) are life-threatening reactions. The strong association between the HLA-B∗58 : 01 allele and allopurinol-induced SCARs is well recognized. Screening for HLA-B∗58 : 01 allele before prescribing allopurinol in some populations has been recommended. Several single-nucleotide polymorphisms (SNPs) in chromosome 6 have been found to be tightly linked wit...
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