Qianyu Wang1, Shusen Sun2, Meng Xie1, Kun Zhao3, Xingang Li4, Zhigang Zhao5. 1. Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 2. College of Pharmacy, Western New England University, Springfield, MA, United States. 3. Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; College of Pharmacy, Western New England University, Springfield, MA, United States. 4. Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. Electronic address: lxg198320022003@163.com. 5. Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. Electronic address: 1022zzg@sina.com.
Abstract
PURPOSE: From our current understanding, the association between the human leukocyte antigen (HLA), HLA-B*1502, and carbamazepine(CBZ)-induced Stevens-Jonson syndrome and toxic epidermal necrolysis (SJS/TEN) in the Asian population is quite clear. However the relationship between other HLA-B alleles and CBZ-induced severe cutaneous adverse drug reactions (SCADRs) remains unclear. We aimed to identify other non-HLA-B*1502 alleles in patients with CBZ-induced SCADRs through a meta-analysis. MATERIALS AND METHODS: A thorough literature search was performed using Embase, PubMed, Web of Knowledge and Cochrane databases. A meta-analysis was performed from their inceptions to May 31, 2016. Studies investigating the association of HLA-B alleles and CBZ-induced SJS/TEN were retrieved. Two reviewers independently extracted the data. Overall odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated using the RevMan 5.3 software. RESULTS: A total of 11 studies met the inclusion criteria, totaling 343 CBZ-induced SJS/TEN cases, 838 CBZ tolerant controls, and 978 population controls. We observed HLA-B*1511 as a risk marker, and HLA-B*4001 and HLA-B*4601 as protective markers for the development of SJS/TEN in patients taking CBZ. SJS/TEN cases were found to be significantly associated with HLA-B*1511 in both the tolerant group (OR=17.43;95%CI=3.12-97.41;P=0.001) and the population-control group (OR=11.11; 95%CI=2.62-47.09; P=0.001). The sensitivity analysis found that HLA-B*5801 was a protective marker in the Southeast Asian population (OR=0.23; 95%CI=0.09-0.58; P=0.002). CONCLUSION: Our study demonstrated that in the Asian population, HLA-B*4001, HLA-B*4601, HLA-B*5801 were strong protective factors in the development of CBZ-induced SJS/TEN whereas HLA-B*1511 was a risk factor. While more studies may be needed in order to confirm these findings, consideration should be taken into testing Asian patients for at-risk alleles prior to CBZ therapy initiation.
PURPOSE: From our current understanding, the association between the human leukocyte antigen (HLA), HLA-B*1502, and carbamazepine(CBZ)-induced Stevens-Jonson syndrome and toxic epidermal necrolysis (SJS/TEN) in the Asian population is quite clear. However the relationship between other HLA-B alleles and CBZ-induced severe cutaneous adverse drug reactions (SCADRs) remains unclear. We aimed to identify other non-HLA-B*1502 alleles in patients with CBZ-induced SCADRs through a meta-analysis. MATERIALS AND METHODS: A thorough literature search was performed using Embase, PubMed, Web of Knowledge and Cochrane databases. A meta-analysis was performed from their inceptions to May 31, 2016. Studies investigating the association of HLA-B alleles and CBZ-induced SJS/TEN were retrieved. Two reviewers independently extracted the data. Overall odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated using the RevMan 5.3 software. RESULTS: A total of 11 studies met the inclusion criteria, totaling 343 CBZ-induced SJS/TEN cases, 838 CBZ tolerant controls, and 978 population controls. We observed HLA-B*1511 as a risk marker, and HLA-B*4001 and HLA-B*4601 as protective markers for the development of SJS/TEN in patients taking CBZ. SJS/TEN cases were found to be significantly associated with HLA-B*1511 in both the tolerant group (OR=17.43;95%CI=3.12-97.41;P=0.001) and the population-control group (OR=11.11; 95%CI=2.62-47.09; P=0.001). The sensitivity analysis found that HLA-B*5801 was a protective marker in the Southeast Asian population (OR=0.23; 95%CI=0.09-0.58; P=0.002). CONCLUSION: Our study demonstrated that in the Asian population, HLA-B*4001, HLA-B*4601, HLA-B*5801 were strong protective factors in the development of CBZ-induced SJS/TEN whereas HLA-B*1511 was a risk factor. While more studies may be needed in order to confirm these findings, consideration should be taken into testing Asian patients for at-risk alleles prior to CBZ therapy initiation.
Authors: Farhana Islam; Daniel Hain; David Lewis; Rebecca Law; Lisa C Brown; Julie-Anne Tanner; Daniel J Müller Journal: Pharmacogenomics J Date: 2022-06-16 Impact factor: 3.245