Evaluating the effect of screening dual HLA-A*31:01 and HLA-B*15:02 alleles by multiplex real-time PCR technique on reducing the risk of Carbamazepine-induced hypersensitivity reactions

Abstract

Human leukocyte antigen (HLA) gene polymorphisms HLA-A*31:01 and HLA-B*15:02 are strongly associated with Carbamazepine (CBZ)-induced severe cutaneous adverse reactions (SCARs). As a result, it is recommended to screen these two alleles before CBZ therapy to reduce the risk of drug allergy. In this study, the authors applied the simultaneous screening test for HLA-A*31:01 and HLA-B*15:02 alleles by multiplex real-time PCR Taqman LNA probe with high sensitivity and specificity in 35 patients that were diagnosed with neurological diseases. Among thirteen patients (37.14% of total) who were positive for single or dual HLA-B*15:02 and HLA-A*31:01 alleles were prescribed alternatives
to CBZ and monitored for adverse events, only one patient had a mild skin adverse reaction after 24 days using Trileptal (Oxcarbazepine) at a dose of 600 mg/day, 12 patients had no symptoms or allergic reactions. The remaining negative patients showed good tolerance to CBZ therapy without any allergy symptoms. Compared to the data of 30 control samples carrying these one or two alleles and 21 patients exhibiting CBZ-induced severe hypersensitivity reactions (OR=28, 95%CI: 3.15-248.78), these results confirm the importance of screening for HLA-A*31:01 and HLA-B*15:02 alleles
before using CBZ in neurological diseases treatment to reduce SCAR rates by replacing CBZ with another drug in patients positive for one of these two alleles.