Dataset Information

Genotyping HLA-B*5801 for Allopurinol-Induced Severe Cutaneous Adverse Reactions: An Accurate and Prompt Method.

ABSTRACT: A new method of HLA-B*5801 genotyping was compared with sequence-based typing (SBT) to find an accurate and prompt method in genotyping HLA-B*5801.Two groups of patients from allopurinol-induced cutaneous adverse reactions (SCARs) and allopurinol-tolerant were both genotyped with PG5801 kit and SBT method. The genotyping results of HLA-B*5801 were compared between the two groups.The PG5801 detection kit results were 100% (79/79) in agreement with the SBT genotyping results for identifying the HLA-B*5801 (+) patients. No false-positive or false-negative errors were found. The sensitivity, specificity, rate of adherence, positive predictive value (PPV) and negative predictive value (NPV) were 100%.The potential fast screening method is an ideal tool to rule out the high-risk allopurinol-induced SCARs patients.

SUBMITTER: Cheng L

PROVIDER: S-EPMC5351112 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Genotyping HLA-B*5801 for Allopurinol-Induced Severe Cutaneous Adverse Reactions: An Accurate and Prompt Method.

Cheng Lin L Zhang Lihua L Gao Lichen L Zhang Wei W Chen Xiaoping X Zhou Hong-Hao HH

Clinical and translational science 20151214 6

<h4>Objectives</h4>A new method of HLA-B*5801 genotyping was compared with sequence-based typing (SBT) to find an accurate and prompt method in genotyping HLA-B*5801.<h4>Methods</h4>Two groups of patients from allopurinol-induced cutaneous adverse reactions (SCARs) and allopurinol-tolerant were both genotyped with PG5801 kit and SBT method. The genotyping results of HLA-B*5801 were compared between the two groups.<h4>Results</h4>The PG5801 detection kit results were 100% (79/79) in agreement wit ...[more]

PMID: 26663557

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Project description:ObjectiveTo 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.DesignNational prospective cohort study.Setting15 medical centres in different regions of Taiwan, from July 2009 to August 2014.Participants2926 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 measuresIncidence of allopurinol induced SCARs with and without screening.ResultsParticipants 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).ConclusionsProspective 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.

Project description:Allopurinol-related severe cutaneous adverse reactions (SCARs) are strongly associated with HLA-B*58:01, the allele frequency (AF) of which is largely different among East Asians. However, evidence of population differences in SCAR development and relevance of genetic and/or other risk factors in the real-world remain unelucidated. This study aimed to evaluate population differences in allopurinol-related SCAR incidence related to genetic and/or other risk factors among East Asians in the real-world. A population-based cohort study was conducted using claims databases from Taiwan, Korea, and Japan. New users of allopurinol (311,846; 868,221; and 18,052 in Taiwan, Korea, and Japan, respectively) were followed up to 1 year. As control drugs, phenytoin and carbamazepine were used. The crude incidence rate ratios (IRRs) of SCARs for allopurinol against phenytoin or carbamazepine were the highest in Taiwan (IRR, 0.62 and 1.22; 95% confidence interval [CI], 0.54-0.72 and 1.01-1.47, respectively), followed by Korea (IRR, 0.34 and 0.82; 95% CI, 0.29-0.40 and 0.77-0.87), and the lowest in Japan (IRR, 0.04 and 0.16; 95% CI, 0.02-0.08 and 0.09-0.29). This order was accordant with that of AF ratios (AFRs) reported of HLA-B*58:01 against alleles responsible for phenytoin- or carbamazepine-related SCARs. The IRRs were higher in patients with chronic kidney disease, females, and elderly. This study demonstrated population differences in the risk of allopurinol-related SCAR development among East Asians based on genetic and other common risk factors. This finding will help to promote appropriate risk management for allopurinol-related SCARs based on ethnic origins. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THIS TOPIC? Allopurinol-related severe cutaneous adverse reactions (SCARs) are strongly associated with HLA-B*58:01, the allele frequency of which is largely different among East Asians. However, there is no direct real-world evidence of population differences in SCAR development and the influence of genetic factors and/or other risk factors. WHAT QUESTION DID THIS STUDY ADDRESS? Do population differences in development of allopurinol-related SCARs, depending on genetic factors and/or other risk factors, exist among three East Asians in the real-world? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? The current analysis, based on comparisons of relative risks of SCAR incidence, provides real-world evidence of population differences in allopurinol-related SCAR development risk among East Asians, which was consistent with differences in reported HLA-B*58:01 frequencies, as well as identifying chronic kidney disease, female gender, and old age as common risk factors. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? This study helps to promote appropriate risk management strategies for allopurinol-related SCARs in the real-world considering risk factors based on the patients' ethnicity. Our approach is useful for evaluating population differences in the real-world.

Dataset Information

Genotyping HLA-B*5801 for Allopurinol-Induced Severe Cutaneous Adverse Reactions: An Accurate and Prompt Method.

Publications

Genotyping HLA-B*5801 for Allopurinol-Induced Severe Cutaneous Adverse Reactions: An Accurate and Prompt Method.

Similar Datasets

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