Real-world evidence of population differences in allopurinol-related severe cutaneous adverse reactions in East Asians: A population-based cohort study

Tsugumichi Sato, Ching Lan Cheng, Heung Woo Park, Yea Huei Kao Yang, Min Suk Yang, Mizuki Fujita, Yuji Kumagai, Masahiro Tohkin, Yoshiro Saito, Kimie Sai

研究成果: Article同行評審

9 引文 斯高帕斯(Scopus)

摘要

Abstract: 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.

原文English
頁(從 - 到)1002-1014
頁數13
期刊Clinical and Translational Science
14
發行號3
DOIs
出版狀態Published - 2021 5月

All Science Journal Classification (ASJC) codes

  • 一般神經科學
  • 一般生物化學,遺傳學和分子生物學
  • 藥理學、毒理學和藥劑學 (全部)

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