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

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 fac...

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Detalles Bibliográficos
Autores principales: Sato, Tsugumichi, Cheng, Ching‐Lan, Park, Heung‐Woo, Kao Yang, Yea‐Huei, Yang, Min‐Suk, Fujita, Mizuki, Kumagai, Yuji, Tohkin, Masahiro, Saito, Yoshiro, Sai, Kimie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212744/
https://www.ncbi.nlm.nih.gov/pubmed/33382928
http://dx.doi.org/10.1111/cts.12964
Descripción
Sumario: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 WHAT QUESTION DID THIS STUDY ADDRESS? 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 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.