1. Real‐world evidence of population differences in allopurinol‐related severe cutaneous adverse reactions in East Asians: A population‐based cohort study
- Author
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Min Suk Yang, Yea Huei Kao Yang, Heung-Woo Park, Yoshiro Saito, Kimie Sai, Mizuki Fujita, Yuji Kumagai, Tsugumichi Sato, Masahiro Tohkin, and Ching Lan Cheng
- Subjects
Male ,Gout ,Scars ,Severity of Illness Index ,Gene Frequency ,Japan ,Risk Factors ,General Pharmacology, Toxicology and Pharmaceutics ,Child ,Aged, 80 and over ,education.field_of_study ,Incidence ,General Neuroscience ,Incidence (epidemiology) ,Articles ,General Medicine ,Middle Aged ,Child, Preschool ,Female ,Drug Eruptions ,Public aspects of medicine ,RA1-1270 ,medicine.symptom ,Cohort study ,Adult ,Adolescent ,Allopurinol ,Population ,Taiwan ,RM1-950 ,Article ,General Biochemistry, Genetics and Molecular Biology ,Gout Suppressants ,Young Adult ,Asian People ,Republic of Korea ,medicine ,Humans ,Genetic Predisposition to Disease ,education ,Allele frequency ,Aged ,Retrospective Studies ,business.industry ,Research ,Infant, Newborn ,Infant ,medicine.disease ,Confidence interval ,HLA-B Antigens ,Relative risk ,Therapeutics. Pharmacology ,business ,Follow-Up Studies ,Demography ,Kidney disease - 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.
- Published
- 2021