title: TheHLA-A*31:01allele: influence on carbamazepine treatment.
abstract: Carbamazepine (CBZ) is an effective anticonvulsant that can sometimes cause hypersensitivity reactions that vary in frequency and severity. Strong associations have been reported between specific human leukocyte antigen (HLA) alleles and susceptibility to CBZ hypersensitivity reactions. Screening forHLA-B*15:02is mandated in patients from South East Asia because of a strong association with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).HLA-A*31:01predisposes to multiple phenotypes of CBZ hypersensitivity including maculopapular exanthema, hypersensitivity syndrome, and SJS/TEN in a range of populations including Europeans, Japanese, South Koreans and Han Chinese, although the effect size varies between the different phenotypes and populations. Between 47 Caucasians and 67 Japanese patients would need to be tested forHLA-A*31:01in order to avoid a single case of CBZ hypersensitivity. A cost-effectiveness study has demonstrated thatHLA-A*31:01screening would be cost-effective. Patient preference assessment has also revealed that patients prefer pharmacogenetic screening and prescription of alternative anticonvulsants compared to current standard of practice without pharmacogenetic testing. For patients who test positive forHLA-A*31:01, alternative treatments are available. When alternatives have failed or are unavailable,HLA-A*31:01testing can alert clinicians to 1) patients who are at increased risk of CBZ hypersensitivity who can then be targeted for more intensive monitoring and 2) increase diagnostic certainty in cases where hypersensitivity has already occurred, so patients can be advised to avoid structurally related drugs in the future. On the basis of the current evidence, we would favor screening all patients forHLA-A*31:01andHLA-B*15:02prior to starting CBZ therapy.
authors.affiliation: MRC Centre for Drug Safety Science, Institute of Translational Medicine, Department of Molecular and Clinical Pharmacology, University of Liverpool; Department of Clinical Pharmacology, The Royal Liverpool and Broadgreen University Hospital NHS Trust, Liverpool, UK.
authors.forename: Vincent Lai Ming
authors.initials: VL
authors.lastname: Yip
authors.affiliation: MRC Centre for Drug Safety Science, Institute of Translational Medicine, Department of Molecular and Clinical Pharmacology, University of Liverpool; Department of Clinical Pharmacology, The Royal Liverpool and Broadgreen University Hospital NHS Trust, Liverpool, UK.
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
keywords: HLA; adverse drug reaction; carbamazepine; hypersensitivity; oxcarbazepine; pharmacogenetics