A003: Enhanced HLA-B*15:02 Screening Before Carbamazepine Therapy in Vietnam: Advancements in Real-Time PCR TaqMan Probe Procedure

Statement of Purpose, Innovation or Hypothesis: Carbamazepine (CBZ) is a widely prescribed antiepileptic and mood stabilizing medication, used globally for various neurological and psychiatric conditions. However, its administration is associated with a risk of severe adverse drug reactions, notably Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Pharmacogenetic studies have identified a strong association between the HLA-B15:02 allele and CBZ-induced SJS/TEN, particularly among Asian populations, including those in Vietnam. Consequently, pre-prescription screening for HLA-B15:02 has become increasingly vital in clinical practice to prevent these potentially life-threatening reactions. However, until now the application of HLA-B screening in patients using CBZ in Vietnam has only stopped at research and genetic centers and has not been widely applied. The aim of our study was to design a TaqMan probe-based, real-time RT-PCR assay for detection of HLA-B*1502 and to determine the frequency of HLA-B*1502 in patients who used Carbamazepine for the first time in psychiatric hospitals, Vietnam.

Description of Methods & Materials: Procedure for determining genotype using Realtime – PCR technique was performed through 4 steps: 1) Analysis of database of HLA-B; (2) IDT's PrimerQuest Tool primer design (covering HLA-B*1502 genes); (3) Compare specific primers on NCBI blast; (4) optimize the process (heat, mix, percentage of primer, substrate). Validation of the enhanced procedure through comparison with established methods, assessing specificity, sensitivity, and reproducibility. Criteria for selecting patients to be screened HLA-B*15:02 were patients prescribed CBZ for the first time. A retrospective survey was conducted at the same time to estimate the rate of SCARs in a group of patients using CBZ. Clinical manifestations and laboratory findings were recorded for each subject in test group.

Data & Results: 100 patients indicating CBZ for the first time were enrolled in test group who was screening with HLA-B∗15:02.The incidence of SCARs in the group of patients whose HLA-B∗15:02 genotype was not determined was 12% through our retrospective survey. However, this rate was only 1% in the group that performed genotype screening of HLA-B∗15:02 (p-value < 0.001). The result showed that 27.5% patients in test group carried the HLA-B*1502 allele and were advised not to take CBZ, indicating a significant portion of the population at risk of adverse reactions to CBZ. The enhanced real-time PCR TaqMan probe procedure demonstrated high specificity and reliability in detecting HLA-B*15:02, thereby validating its utility in clinical settings. In addition to developing and validating the HLA-B*15:02 genotyping method, we also developed a system for transmitting and interpreting results to patients and ordering physicians. Pre-prescription screening for HLA-B15:02 before initiating CBZ therapy in Vietnam is imperative to mitigate the risk of severe adverse reactions.

Interpretation, Conclusion or Significance: The improved real-time PCR TaqMan probe procedure offers a cost-effective, efficient, and reliable method for detecting HLA-B*15:02, suitable for implementation in molecular laboratories across Vietnam. However, challenges such as limited awareness among medical professionals and patients, as well as reimbursement issues, must be addressed to facilitate widespread adoption of HLA-B*15:02 screening in clinical practice. By integrating enhanced screening protocols, Vietnam can enhance patient safety and optimize therapeutic outcomes in CBZ therapy, thereby reducing the burden of adverse drug reactions induced by CBZ on healthcare systems.

Disclosures: The author declares that (s)he has no relevant or material financial interests that relate to the research described in this study

Citations/References: 1. Chung, W.H., C.W. Wang, and R.L. Dao, Severe cutaneous adverse drug reactions. J Dermatol, 2016. 43(7): p. 758-66.

2. Zhang, C., et al., Drug-induced severe cutaneous adverse reactions: Determine the cause and prevention. 2019. 123(5): p. 483-487.

3. Ferrell, P.B. and H.L. McLeod, Carbamazepine, HLA-B* 1502 and risk of Stevens–Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations. 2008.

Additional Information/Authors: We would like to acknowledge all the people that contributed or helped in carrying out this research.