{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:04:18Z","timestamp":1790805858331,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T00:00:00Z","timestamp":1611705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Allopurinol\u2010related severe cutaneous adverse reactions (SCARs) are strongly associated with <jats:italic>HLA<\/jats:italic>\u2010<jats:italic>B*58<\/jats:italic>:<jats:italic>01<\/jats:italic>, 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\u2010world remain unelucidated. This study aimed to evaluate population differences in allopurinol\u2010related SCAR incidence related to genetic and\/or other risk factors among East Asians in the real\u2010world. A population\u2010based 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\u00a0year. 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\u20130.72 and 1.01\u20131.47, respectively), followed by Korea (IRR, 0.34 and 0.82; 95% CI, 0.29\u20130.40 and 0.77\u20130.87), and the lowest in Japan (IRR, 0.04 and 0.16; 95% CI, 0.02\u20130.08 and 0.09\u20130.29). This order was accordant with that of AF ratios (AFRs) reported of <jats:italic>HLA<\/jats:italic>\u2010<jats:italic>B*58<\/jats:italic>:<jats:italic>01<\/jats:italic> against alleles responsible for phenytoin\u2010 or carbamazepine\u2010related SCARs. The IRRs were higher in patients with chronic kidney disease, females, and elderly. This study demonstrated population differences in the risk of allopurinol\u2010related SCAR development among East Asians based on genetic and other common risk factors. This finding will help to promote appropriate risk management for allopurinol\u2010related SCARs based on ethnic origins.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"box\" position=\"anchor\"><jats:caption><jats:title>Study Highlights<\/jats:title><\/jats:caption><jats:p>\n<jats:list list-type=\"simple\">\n\n<jats:list-item><jats:p>\n<jats:bold>WHAT IS THE CURRENT KNOWLEDGE ON THIS TOPIC?<\/jats:bold>\n<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p>Allopurinol\u2010related severe cutaneous adverse reactions (SCARs) are strongly associated with <jats:italic>HLA<\/jats:italic>\u2010<jats:italic>B*58<\/jats:italic>:<jats:italic>01<\/jats:italic>, the allele frequency of which is largely different among East Asians. However, there is no direct real\u2010world evidence of population differences in SCAR development and the influence of genetic factors and\/or other risk factors.\n<jats:list list-type=\"simple\">\n<jats:list-item><jats:p><jats:bold>WHAT QUESTION DID THIS STUDY ADDRESS?<\/jats:bold><\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p>Do population differences in development of allopurinol\u2010related SCARs, depending on genetic factors and\/or other risk factors, exist among three East Asians in the real\u2010world?\n<jats:list list-type=\"simple\">\n<jats:list-item><jats:p><jats:bold>WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?<\/jats:bold><\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p>The current analysis, based on comparisons of relative risks of SCAR incidence, provides real\u2010world evidence of population differences in allopurinol\u2010related SCAR development risk among East Asians, which was consistent with differences in reported <jats:italic>HLA<\/jats:italic>\u2010<jats:italic>B*58<\/jats:italic>:<jats:italic>01<\/jats:italic> frequencies, as well as identifying chronic kidney disease, female gender, and old age as common risk factors.\n<jats:list list-type=\"simple\">\n<jats:list-item><jats:p><jats:bold>HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?<\/jats:bold><\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p>This study helps to promote appropriate risk management strategies for allopurinol\u2010related SCARs in the real\u2010world considering risk factors based on the patients\u2019 ethnicity. Our approach is useful for evaluating population differences in the real\u2010world.<\/jats:p><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/cts.12964","type":"journal-article","created":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T22:38:56Z","timestamp":1609454336000},"page":"1002-1014","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Real\u2010world evidence of population differences in allopurinol\u2010related severe cutaneous adverse reactions in East Asians: A population\u2010based cohort study"],"prefix":"10.1111","volume":"14","author":[{"given":"Tsugumichi","family":"Sato","sequence":"first","affiliation":[{"name":"Department of Pharmacy Faculty of Pharmaceutical Sciences Tokyo University of Science Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching\u2010Lan","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Pharmacy Institute of Clinical Pharmacy and Pharmaceutical Sciences College of Medicine National Cheng Kung University Tainan Taiwan"},{"name":"Department of Pharmacy National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heung\u2010Woo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Seoul National University College of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yea\u2010Huei","family":"Kao Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Institute of Clinical Pharmacy and Pharmaceutical Sciences College of Medicine National Cheng Kung University Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min\u2010Suk","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine SMG\u2010SNU Boramae Medical Center Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuki","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Faculty of Pharmaceutical Sciences Tokyo University of Science Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Kumagai","sequence":"additional","affiliation":[{"name":"Clinical Research Center School of Medicine Kitasato University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Tohkin","sequence":"additional","affiliation":[{"name":"Department of Regulatory Science Graduate School of Pharmaceutical Science Nagoya City University Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiro","family":"Saito","sequence":"additional","affiliation":[{"name":"Division of Medicinal Safety Science National Institute of Health Sciences Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimie","family":"Sai","sequence":"additional","affiliation":[{"name":"Division of Medicinal Safety Science National Institute of Health Sciences Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.DMPK-11-RV-111"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.144"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/2168479013517892"},{"key":"e_1_2_9_5_1","unstructured":"The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use.Ethnic factors in the acceptability a foreign clinical data E5 (R1).https:\/\/database.ich.org\/sites\/default\/files\/E5_R1__Guideline.pdf. c1998. 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