Use of HLA-B∗58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: National prospective cohort study
Journal
BMJ (Online)
Journal Volume
351
Date Issued
2015
Author(s)
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.
Tsai J.-C.
Lai W.-T.
Tsai W.-C.
Yin G.-D.
Ou T.-T.
Cheng K.-H.
Yen J.-H.
Liou T.-L.
Lin T.-H.
Chen D.-Y.
Hsiao P.-J.
Weng M.-Y.
Chen Y.-M.
Chen C.-H.
Liu M.-F.
Yen H.-W.
Lee J.-J.
Kuo M.-C.
Wu C.-C.
Hung S.-Y.
Luo S.-F.
Yang Y.-H.
Chuang H.-P.
Chou Y.-C.
Liao H.-T.
Wang C.-W.
Huang C.-L.
Chang C.-S.
Lee M.-T.M.
Wong C.-S.
Chen C.-H.
Wu J.-Y.
Chen Y.-T.
Shen C.-Y.
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. ? BMJ Publishing Group Ltd 2015.
SDGs
Other Subjects
allopurinol; HLA B antigen; allopurinol; antigout agent; HLA B antigen; HLA-B58 antigen; adolescent; adult; adverse drug reaction; adverse outcome; aged; allele; Article; blister; cohort analysis; disease severity; DNA purification; drug indication; eosinophilia; fatigue; female; fever; follow up; genotype; gout; HLA B gene; human; incidence; major clinical study; male; mouth ulcer; multicenter study; outcome assessment; priority journal; prospective study; pruritus; rash; risk assessment; risk factor; severe cutaneous adverse reaction; skin disease; sore throat; Stevens Johnson syndrome; symptom; Taiwan; Taiwanese; toxic epidermal necrolysis; urticaria; chemically induced; chronic disease; clinical trial; Drug Eruptions; genetic screening; genetics; genotype; heterozygote; middle aged; pruritus; rash; Allopurinol; Chronic Disease; Drug Eruptions; Exanthema; Female; Genetic Testing; Genotype; Gout Suppressants; Heterozygote; HLA-B Antigens; Humans; Male; Middle Aged; Prospective Studies; Pruritus; Taiwan
Publisher
BMJ Publishing Group
Type
journal article