Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study.
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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DOI：
10.1136/bmj.h4848
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发表时间：
2015-09-23
期刊：
影响因子：
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通讯作者：
Taiwan Allopurinol-SCAR Consortium
中科院分区：
文献类型：
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作者：
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 MT;Chen P;Wong CS;Chen CH;Wu JY;Chen YT;Shen CY;Taiwan Allopurinol-SCAR Consortium
目的 评估使用 HLA-B*58:01 等位基因前瞻性筛查来识别台湾个体因别嘌呤醇治疗引起严重皮肤不良反应 (SCAR) 的风险。设计国家前瞻性队列研究。 2009年7月至2014年8月，在台湾不同地区设置15个医疗中心。参与者2926名有别嘌呤醇治疗指征但之前未服用别嘌呤醇的人。如果参与者接受过骨髓移植、不是汉族血统并且有别嘌呤醇诱发的过敏史，则被排除在外。使用从 2910 名参与者的外周血中纯化的 DNA 来评估 HLA-B*58:01 的存在。 主要结果衡量有或没有筛查时别嘌呤醇诱导的 SCAR 的发生率。结果 HLA-B*58:01 检测呈阳性的参与者（19.6%，n=571）被建议避免使用别嘌呤醇，并被转介至替代药物治疗或建议继续进行研究前治疗。测试结果呈阴性的参与者（80.4%，n=2339）被给予别嘌呤醇。参与者每周接受一次采访，持续两个月，以监测症状。采用台湾国民健康保险研究数据库估计的别嘌呤醇引起的 SCAR 的历史发生率进行比较。随访期间，97 名 (3%) 参与者出现了轻度、短暂的皮疹，但没有水疱。没有参与者因药物不良反应而入院。任何接受别嘌呤醇且 HLA-B*58:01 筛查呈阴性的参与者均未出现疤痕。相比之下，根据全国别嘌呤醇引起的 SCAR 历史发病率的估计，预计会出现 7 例 SCAR（每年 0.30%，95% 置信区间 0.28% 至 0.31%；P=0.0026；两侧一样本二项式检验）。结论 在台湾医疗中心，对 HLA-B*58:01 等位基因进行前瞻性筛查，并结合针对携带者的替代药物治疗，可显着降低别嘌呤醇诱发的 SCAR 发生率。
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.