Recommendations for HLA‐B*15:02 and HLA‐A*31:01 genetic testing to reduce the risk of carbamazepine‐induced hypersensitivity reactions

  title={Recommendations for HLA‐B*15:02 and HLA‐A*31:01 genetic testing to reduce the risk of carbamazepine‐induced hypersensitivity reactions},
  author={U Amstutz and Neil H. Shear and Michael J Rieder and Soomi Hwang and Vincent Fung and Hidefumi Nakamura and Mary B. Connolly and Shinya Ito and Bruce C. Carleton},
To systematically review evidence on genetic risk factors for carbamazepine (CBZ)–induced hypersensitivity reactions (HSRs) and provide practice recommendations addressing the key questions: (1) Should genetic testing for HLA‐B*15:02 and HLA‐A*31:01 be performed in patients with an indication for CBZ therapy to reduce the occurrence of CBZ‐induced HSRs? (2) Are there subgroups of patients who may benefit more from genetic testing for HLA‐B*15:02 or HLA‐A*31:01 compared to others? (3) How should… 

The HLA-B*15:02 allele in a Spanish Romani patient with carbamazepine-induced Stevens-Johnson syndrome.

The case of a Spanish Romani patient who developed Stevens-Johnson syndrome upon treatment with CBZ is reported, and in vitro assays confirmed CBZ as the culprit drug.

A novel multiplex polymerase chain reaction assay for detection of both HLA‐A*31:01/HLA‐B*15:02 alleles, which confer susceptibility to carbamazepine‐induced severe cutaneous adverse reactions

A multiplex polymerase chain reaction (PCR) using TaqMan Probe was designed and validated to be able to detect HLA•A*31:01 and HLA‐B*15:02 and had a perfect agreement in the validation group of 125 samples.

HLA-A*31: 01 and HLA-B*15:02 association with Stevens–Johnson syndrome and toxic epidermal necrolysis to carbamazepine in a multiethnic Malaysian population

This study found a new association between HLA-A*31:01 and CBZ-SJS/TEN in Indians, and further investigated the association with HLA/B*15:02 in a multiethnic Malaysian population by comparing carrier frequencies of the alleles.

Implementation of HLA-B*15:02 Genotyping as Standard-of-Care for Reducing Carbamazepine/Oxcarbazepine Induced Cutaneous Adverse Drug Reactions in Thailand

The findings of this study showed that the incidence of SCARs of CBZ/OXC was significantly lower in the HLA-B*15:02 screening arm than in the non-screening arm, suggesting that the hospital policy and clinical decision support (CDS) alert system is essential to overcome the barriers associated with the utilization of PGx guidelines into clinical practice.

The HLA-A*31:01 allele: influence on carbamazepine treatment

Screening all patients for HLA-A*31:01 andHLA-B*15:02 prior to starting CBZ therapy would be favors, on the basis of the current evidence.

Cost‐effectiveness of screening for HLA‐A*31:01 prior to initiation of carbamazepine in epilepsy

An economic evaluation of HLA‐A*31:01 testing from the perspective of the National Health Service (NHS) in the United Kingdom found that routine testing of patients with epilepsy is cost‐effective.

An Updated Review of Genetic Associations With Severe Adverse Drug Reactions: Translation and Implementation of Pharmacogenomic Testing in Clinical Practice

The current knowledge of pharmacogenomics of severe ADR, and the potentially clinical use of these genetic markers for avoidance of ADR are summarized.

HLA-A*31:01 and Oxcarbazepine-Induced DRESS in a Patient With Seizures and Complete DCX Deletion

A previously uncharacterized association between the HLA-A*31:01 allele and the DRESS hypersensitivity reaction associated with oxcarbazepine administration is described and the potential utility of preemptive pharmacogenomic screening of patients before pharmacological treatment of epilepsy is discussed.

Genetic risk factors for antiepileptic drug–induced hypersensitivity reactions in Israeli populations

The aim was to estimate the distribution of these alleles in Jewish and Arab populations in Israel and identified SJS‐ or TEN‐related hospitalizations of Jews of Indian descent, which should be considered at greater risk for antiepileptic drug–induced SJS and TEN.

Effects of a HLA-B*15:02 screening policy on antiepileptic drug use and severe skin reactions

The screening policy was associated with prevention of carbamazepine-induced SJS/TEN without reducing the overall burden of AED-induced HLA-B*15:02, likely because of clinicians preferring AEDs that do not require genetic screening but may also induce SJS-TEN.



HLA-A*31:01 and HLA-B*15:02 as genetic markers for carbamazepine hypersensitivity in children

This study is the first to demonstrate the association of HLA‐A*31:01 with CBZ hypersensitivity in children, providing important replication of this association and highlighting the importance of Hla‐A-31: 01 as a predictive biomarker across various ancestries.

Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA‐B Genotype and Carbamazepine Dosing

The purpose of this article is to provide information to allow the interpretation of clinical HLA‐B*15:02 genotype tests so that the results can be used to guide the use of carbamazepine.

Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA‐B Genotype and Abacavir Dosing

Recommendations are provided for the use of abacavir based on HLA‐B genotype based on genetic prescreening for patients at increased risk of a hypersensitivity reaction to the anti‐HIV drug abacvir.

HLA Class I markers in Japanese patients with carbamazepine‐induced cutaneous adverse reactions

Examination of HLA class I in Japanese patients with severe cADRs may suggest that HLA‐B*5901 is one of the candidate markers for CBZ‐induced SJS in Japanese, which is reported recently that the human leukocyte antigen HLA*1502 is associated with Stevens‐Johnson syndrome in Han Chinese.

Association between HLA‐B*1502 and carbamazepine‐induced severe cutaneous adverse drug reactions in a Thai population

Results from this study suggest that HLA‐B*1502 may be a useful pharmacogenetic test for screening Thai individuals who may be at risk for CBZ‐induced SJS and TEN.

Association between HLA and Stevens–Johnson Syndrome Induced by Carbamazepine in Southern Han Chinese: Genetic Markers besides B*1502?

Given the association between HLA‐B*1502 and CBZ‐induced SJS/TEN, genetic testing before initiating CBZ therapy is suggested in Han Chinese population, and physicians should also be vigilant about SJS /TEN in those negative for HLA•B* 1502.

Association between HLA‐B*1502 Allele and Antiepileptic Drug‐Induced Cutaneous Reactions in Han Chinese

Identification of genetic polymorphisms predisposing to development of AED‐induced SCR offers the possibility of avoiding these high‐risk drugs in genetically susceptible individuals.

HLA‐B*1511 is a risk factor for carbamazepine‐induced Stevens‐Johnson syndrome and toxic epidermal necrolysis in Japanese patients

The genotyped the HLA‐B locus from 14 Japanese typical and atypical SJS/TEN patients in whom carbamazepine was considered to be involved in the onset of adverse reactions and suggested that HLA·B*1511, a member of HLA•B75, is a risk factor for carbamazepsine‐induced SJS /TEN in Japanese.

HLA Genotype and Carbamazepine‐Induced Cutaneous Adverse Drug Reactions: A Systematic Review

It is suggested that HLA testing before carbamazepine therapy would be effective at identifying individuals at risk of hypersensitivity and applicable to multiple populations providing hope for prevention in the future.

Strong association between HLA-B*1502 and carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in mainland Han Chinese patients

The results suggest that HLA-B*1502 is strongly associated with CBZ-induced SJS/TEN in the whole Han Chinese population.