FPIN's Clinical Inquiries
Should Allele Testing Be Done Before Prescribing Allopurinol to Prevent Severe Cutaneous Adverse Reactions?
Am Fam Physician. 2021 Nov ;104(5):513-514.
Should allele testing be done before prescribing allopurinol to prevent severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms?
Moderate evidence supports allele testing for HLA-B*58:01 before initiating allopurinol to decrease the incidence of SCARs in higher risk populations. (Strength of Recommendation [SOR]: B, based on systematic review and meta-analysis of population-controlled studies, prospective cohort studies.) Patient populations who are not at increased risk should not be screened. (SOR: C, based on consensus recommendation.)
A 2015 nonrandomized prospective cohort study (n = 2,926) evaluated the use of prospective genotyping for HLA-B*58:01 before initiation of allopurinol to prevent SCARs, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and others.1 Historical incidence was used for the control group. The study included 15 medical centers in various regions across Taiwan from July 2009 to August 2014. Exclusion criteria included individuals who had a history of allopurinol-induced hypersensitivity, had a history of bone marrow transplant, or were not of self-described Han Chinese descent. HLAB*58:01 genotyping with real-time polymerase chain reaction was performed before starting treatment with allopurinol for all patients, and all patients were counseled on SCARs, with HLA-B*58:01-positive patients (n = 571) being recommended alternative treatments and non-carriers (n = 2,339) being started on allopurinol. The mean estimated historical incidence of allopurinol-induced SCARs in the control group from 2001 to 2004 was 0.30% per year (95% CI, 0.28% to 0.31%). This range of years was used to prevent confounding with early adopters of pretreatment genotyping. This study had a sufficient number of patients for a power of 86% to detect
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1. Ko TM, Tsai CY, Chen SY, et al.; Taiwan Allopurinol-SCAR Consortium. Use of HLA-B*58: 01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study. BMJ. 2015;351:h4848....
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