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

Amstutz, Ursula; Shear, Neil H.; Rieder, Michael J.; Hwang, Soomi; Fung, Vincent; Nakamura, Hidefumi; Connolly, Mary B.; Ito, Shinya; Carleton, Bruce C.; Canadian Pharmacogenomics Network for Drug Safety clinical recommendation group

Wiley

Objective: 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, in order to reduce the occurrence of CBZ-induced HSRs? (2) Are there subgroups of patients who may benefit more from genetic testing for HLAB* 15:02 or HLA-A*31:01 compared to others? (3) How should patients with an indication for CBZ therapy be managed based on their genetic test results? Methods: A systematic literature search was performed for HLA-B*15:02 and HLA-A*31:01 and their association with CBZ-induced HSRs. Evidence was critically appraised and clinical practice recommendations were developed based on expert group consensus. Results: Patients carrying HLA-B*15:02 are at strongly increased risk for CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in populations where HLA-B*15:02 is common, but not CBZ-induced hypersensitivity syndrome (HSS) or maculopapular exanthema (MPE). HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported from Asian countries only, including China, Thailand, Malaysia, and India. HLA-B*15:02 is very rare in Caucasians or Japanese where no HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported so far. HLA-A*31:01-positive patients are at increased risk for CBZ-induced HSS and MPE, and possibly SJS/TEN and acute generalized exanthematous pustulosis (AGEP). This association has been shown in Caucasian, Japanese, Korean, Chinese, and patients of mixed origin; however, HLA-A*31:01 is common in most ethnic groups. Not all patients carrying either risk variant develop a HSR, resulting in a relatively low positive predictive value of the genetic tests.

Article

eng

Vancouver : University of British Columbia Library

10.14288/1.0355759

Medicine, Faculty of; Pharmaceutical Sciences, Faculty of; Non UBC; Medicine, Department of; Neurology, Division of; Pathology and Laboratory Medicine, Department of; Pediatrics, Department of

10.1111/epi.12564

Faculty

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