TY - JOUR
T1 - Hypersensitivity and cardiovascular risks related to allopurinol and febuxostat therapy in Asians
T2 - A population-based cohort study and meta-analysis
AU - Chen, Chi-Hua
AU - Chen, Chun-Bing
AU - Chang, Chee Jen
AU - Lin, Yu Jr
AU - Wang, Chuang-Wei
AU - Chi, Ching-Chi
AU - Lu, Chun-Wei
AU - Chen, Wei-Ti
AU - Pan, Ren-You
AU - Su, Shih-Chi
AU - Hsu, Lung-An
AU - Chang, Ya-Ching
AU - Yu, Kuang-Hui
AU - Wu, Yeong-Jian Jan
AU - Lin, Ko-Ming
AU - Hung, Shuen-Iu
AU - Chen, Shin-Ming
AU - Chung, Wen-Hung
N1 - Funding Information:
This study was supported by grants from the Ministry of Science and Technology, Taiwan (MOST-104-2314-B-182A-148-MY3, MOST-104-2325-B-182A-006, MOST-105-2325-B-182A-007-, MOST-106-2314-B-182A-037-MY3, MOST-106-2622-B-182A-003-CC2, MOST-107-2622-B-182A-001-CC2 to WH Chung); Chang Gung Memorial Hospital, Linkou, Taiwan (CIRPD1D0031, CIRPD1D0032 to CJ Chang; CLRPG2E0053, CMRPG3D0363, CORPG3F0042~3, OMRPG3E0041 to WH Chung); Chang Gung Memorial Hospital, Keelung, Taiwan (CMRPG2H0081 to CB Chen) and Astellas Pharma Taiwan. The funding organization had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. In addition, we thank the Research Services Center for Health Information, Chang Gung University, Taoyuan, and Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan, for their analytic support in this study.
Publisher Copyright:
© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics
PY - 2019/8
Y1 - 2019/8
N2 - The safety of newer xanthine oxidase inhibitor febuxostat compared to allopurinol remains unclear. To compare the risks of allopurinol hypersensitivity and febuxostat hypersensitivity and cardiovascular diseases (CVDs) in Asians, we conducted a population-based cohort study enrolling patients receiving allopurinol or febuxostat from Chang Gung Memorial Hospital Health System across Taiwan during 2012–2016 and further performed a meta-analysis incorporating two recent studies. Among the 61,539 users, a corresponding 12,007 and 5,680 patients were identified as new users. The overall incidence of febuxostat hypersensitivity was significantly lower than allopurinol hypersensitivity (0.2 vs. 2.7 per 1,000 new users; P < 0.001). There were 33 allopurinol-hypersensitivity reactions (including 18 severe cutaneous adverse drug reactions), and only one patient developed febuxostat-maculopapular exanthema. Moreover, febuxostat did not statistically increase the risk of CVD (hazard ratio (HR), 1.16; P = 0.152) and related death (HR, 1.49; P = 0.496) compared to allopurinol. The result of the meta-analysis also showed a consistent result. In conclusion, the incidence and severity of febuxostat-hypersensitivity are lower than with allopurinol. Febuxostat did not show an increased risk of CVD and related death.
AB - The safety of newer xanthine oxidase inhibitor febuxostat compared to allopurinol remains unclear. To compare the risks of allopurinol hypersensitivity and febuxostat hypersensitivity and cardiovascular diseases (CVDs) in Asians, we conducted a population-based cohort study enrolling patients receiving allopurinol or febuxostat from Chang Gung Memorial Hospital Health System across Taiwan during 2012–2016 and further performed a meta-analysis incorporating two recent studies. Among the 61,539 users, a corresponding 12,007 and 5,680 patients were identified as new users. The overall incidence of febuxostat hypersensitivity was significantly lower than allopurinol hypersensitivity (0.2 vs. 2.7 per 1,000 new users; P < 0.001). There were 33 allopurinol-hypersensitivity reactions (including 18 severe cutaneous adverse drug reactions), and only one patient developed febuxostat-maculopapular exanthema. Moreover, febuxostat did not statistically increase the risk of CVD (hazard ratio (HR), 1.16; P = 0.152) and related death (HR, 1.49; P = 0.496) compared to allopurinol. The result of the meta-analysis also showed a consistent result. In conclusion, the incidence and severity of febuxostat-hypersensitivity are lower than with allopurinol. Febuxostat did not show an increased risk of CVD and related death.
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U2 - 10.1002/cpt.1377
DO - 10.1002/cpt.1377
M3 - Article
C2 - 30690722
VL - 106
SP - 391
EP - 401
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
SN - 0009-9236
IS - 2
ER -
