Association between the HLA-B alleles and carbamazepine-induced SJS/TEN: A meta-analysis

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.

Keywords: Carbamazepine; Human leukocyte antigen; Meta-analysis; Stevens-Johnson syndrome; Toxic epidermal necrolysis.