Use of HLA-B58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: National prospective cohort study

Tai Ming Ko, Chang Youh Tsai, Shih Yang Chen, Kuo Shu Chen, Kuang Hui Yu, Chih Sheng Chu, Chung Ming Huang, Chrong Reen Wang, Chia Tse Weng, Chia Li Yu, Song Chou Hsieh, Jer Chia Tsai, Wen Ter Lai, Wen Chan Tsai, Guang Dar Yin, Tsan Teng Ou, Kai Hung Cheng, Jeng Hsien Yen, Teh Ling Liou, Tsung Hsien LinDer Yuan Chen, Pi Jung Hsiao, Meng Yu Weng, Yi Ming Chen, Chen Hung Chen, Ming Fei Liu, Hsueh Wei Yen, Jia Jung Lee, Mei Chuan Kuo, Chen Ching Wu, Shih Yuan Hung, Shue Fen Luo, Ya Hui Yang, Hui Ping Chuang, Yi Chun Chou, Hung Ting Liao, Chia Wen Wang, Chun Lin Huang, Chia Shuo Chang, Ming Ta Michael Lee, Pei Chen, Chih Shung Wong, Chien Hsiun Chen, Jer Yuarn Wu, Yuan Tsong Chen, Chen Yang Shen

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102 Citations (Scopus)

Abstract

OBJECTIVE: To evaluate the use of prospective screening for the HLA-B58:01 allele to identify Taiwanese individuals at risk of severe cutaneous adverse reactions (SCARs) induced by allopurinol treatment. DESIGN: National prospective cohort study. SETTING: 15 medical centres in different regions of Taiwan, from July 2009 to August 2014. PARTICIPANTS: 2926 people who had an indication for allopurinol treatment but had not taken allopurinol previously. Participants were excluded if they had undergone a bone marrow transplant, were not of Han Chinese descent, and had a history of allopurinol induced hypersensitivity. DNA purified from 2910 participants' peripheral blood was used to assess the presence of HLA-B58:01. MAIN OUTCOME MEASURES: Incidence of allopurinol induced SCARs with and without screening. RESULTS: Participants who tested positive for HLA-B58:01 (19.6%, n=571) were advised to avoid allopurinol, and were referred to an alternate drug treatment or advised to continue with their prestudy treatment. Participants who tested negative (80.4%, n=2339) were given allopurinol. Participants were interviewed once a week for two months to monitor symptoms. The historical incidence of allopurinol induced SCARs, estimated by the National Health Insurance research database of Taiwan, was used for comparison. Mild, transient rash without blisters developed in 97 (3%) participants during follow-up. None of the participants was admitted to hospital owing to adverse drug reactions. SCARs did not develop in any of the participants receiving allopurinol who screened negative for HLA-B58:01. By contrast, seven cases of SCARs were expected, based on the estimated historical incidence of allopurinol induced SCARs nationwide (0.30% per year, 95% confidence interval 0.28% to 0.31%; P=0.0026; two side one sample binomial test). CONCLUSIONS: Prospective screening of the HLA-B58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres.

Original languageEnglish
Article numberh4848
JournalBMJ (Online)
Volume351
DOIs
Publication statusPublished - 2015 Sep 23

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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