Use of HLA-B∗58:01 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 Lin; Der 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

doi:10.1136/bmj.h4848

Use of HLA-B^∗58:01 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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Abstract

OBJECTIVE: To evaluate the use of prospective screening for the HLA-B^∗58:01 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-B^∗58:01. MAIN OUTCOME MEASURES: Incidence of allopurinol induced SCARs with and without screening. RESULTS: Participants who tested positive for HLA-B^∗58:01 (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-B^∗58:01. 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-B^∗58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres.

Original language	English
Article number	h4848
Journal	BMJ (Online)
Volume	351
DOIs	https://doi.org/10.1136/bmj.h4848
Publication status	Published - 2015 Sept 23

All Science Journal Classification (ASJC) codes

General Medicine

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10.1136/bmj.h4848

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Ko, T. M., Tsai, C. Y., Chen, S. Y., Chen, K. S., Yu, K. H., Chu, C. S., Huang, C. M., Wang, C. R., Weng, C. T., Yu, C. L., Hsieh, S. C., Tsai, J. C., Lai, W. T., Tsai, W. C., Yin, G. D., Ou, T. T., Cheng, K. H., Yen, J. H., Liou, T. L., ... Shen, C. Y. (2015). Use of HLA-B^∗58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: National prospective cohort study. BMJ (Online), 351, Article h4848. https://doi.org/10.1136/bmj.h4848

@article{1513c6f24ae54ed6acbd1c86af606494,

title = "Use of HLA-B∗58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: National prospective cohort study",

abstract = "OBJECTIVE: To evaluate the use of prospective screening for the HLA-B∗58:01 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-B∗58:01. MAIN OUTCOME MEASURES: Incidence of allopurinol induced SCARs with and without screening. RESULTS: Participants who tested positive for HLA-B∗58:01 (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-B∗58:01. 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-B∗58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres.",

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

note = "Publisher Copyright: {\textcopyright} BMJ Publishing Group Ltd 2015.",

year = "2015",

month = sep,

day = "23",

doi = "10.1136/bmj.h4848",

language = "English",

volume = "351",

journal = "BMJ (Online)",

issn = "0959-8146",

publisher = "BMJ Publishing Group",

}

Ko, TM, Tsai, CY, Chen, SY, Chen, KS, Yu, KH, Chu, CS, Huang, CM, Wang, CR , Weng, CT, Yu, CL, Hsieh, SC, Tsai, JC, Lai, WT, Tsai, WC, Yin, GD, Ou, TT, Cheng, KH, Yen, JH, Liou, TL, Lin, TH, Chen, DY, Hsiao, PJ, Weng, MY, Chen, YM, Chen, CH, Liu, MF, Yen, HW, Lee, JJ, Kuo, MC, Wu, CC, Hung, SY, Luo, SF, Yang, YH, Chuang, HP, Chou, YC, Liao, HT, Wang, CW, Huang, CL, Chang, CS, Lee, MTM, Chen, P, Wong, CS, Chen, CH, Wu, JY, Chen, YT & Shen, CY 2015, 'Use of HLA-B^∗58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: National prospective cohort study', BMJ (Online), vol. 351, h4848. https://doi.org/10.1136/bmj.h4848

TY - JOUR

T1 - Use of HLA-B∗58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan

T2 - National prospective cohort study

AU - Ko, Tai Ming

AU - Tsai, Chang Youh

AU - Chen, Shih Yang

AU - Chen, Kuo Shu

AU - Yu, Kuang Hui

AU - Chu, Chih Sheng

AU - Huang, Chung Ming

AU - Wang, Chrong Reen

AU - Weng, Chia Tse

AU - Yu, Chia Li

AU - Hsieh, Song Chou

AU - Tsai, Jer Chia

AU - Lai, Wen Ter

AU - Tsai, Wen Chan

AU - Yin, Guang Dar

AU - Ou, Tsan Teng

AU - Cheng, Kai Hung

AU - Yen, Jeng Hsien

AU - Liou, Teh Ling

AU - Lin, Tsung Hsien

AU - Chen, Der Yuan

AU - Hsiao, Pi Jung

AU - Weng, Meng Yu

AU - Chen, Yi Ming

AU - Chen, Chen Hung

AU - Liu, Ming Fei

AU - Yen, Hsueh Wei

AU - Lee, Jia Jung

AU - Kuo, Mei Chuan

AU - Wu, Chen Ching

AU - Hung, Shih Yuan

AU - Luo, Shue Fen

AU - Yang, Ya Hui

AU - Chuang, Hui Ping

AU - Chou, Yi Chun

AU - Liao, Hung Ting

AU - Wang, Chia Wen

AU - Huang, Chun Lin

AU - Chang, Chia Shuo

AU - Lee, Ming Ta Michael

AU - Chen, Pei

AU - Wong, Chih Shung

AU - Chen, Chien Hsiun

AU - Wu, Jer Yuarn

AU - Chen, Yuan Tsong

AU - Shen, Chen Yang

PY - 2015/9/23

Y1 - 2015/9/23

N2 - OBJECTIVE: To evaluate the use of prospective screening for the HLA-B∗58:01 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-B∗58:01. MAIN OUTCOME MEASURES: Incidence of allopurinol induced SCARs with and without screening. RESULTS: Participants who tested positive for HLA-B∗58:01 (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-B∗58:01. 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-B∗58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres.

AB - OBJECTIVE: To evaluate the use of prospective screening for the HLA-B∗58:01 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-B∗58:01. MAIN OUTCOME MEASURES: Incidence of allopurinol induced SCARs with and without screening. RESULTS: Participants who tested positive for HLA-B∗58:01 (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-B∗58:01. 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-B∗58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres.

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DO - 10.1136/bmj.h4848

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JO - BMJ (Online)

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M1 - h4848

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Use of HLA-B^∗58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: National prospective cohort study

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