Wang Qianyu, Sun Shusen, Xie Meng, Zhao Kun, Li Xingang, Zhao Zhigang
Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
College of Pharmacy, Western New England University, Springfield, MA, United States.
Epilepsy Res. 2017 Sep;135:19-28. doi: 10.1016/j.eplepsyres.2017.05.015. Epub 2017 Jun 3.
From our current understanding, the association between the human leukocyte antigen (HLA), HLA-B1502, 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-B1502 alleles in patients with CBZ-induced SCADRs through a meta-analysis.
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.
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-B1511 as a risk marker, and HLA-B4001 and HLA-B4601 as protective markers for the development of SJS/TEN in patients taking CBZ. SJS/TEN cases were found to be significantly associated with HLA-B1511 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).
Our study demonstrated that in the Asian population, HLA-B4001, HLA-B4601, HLA-B5801 were strong protective factors in the development of CBZ-induced SJS/TEN whereas HLA-B1511 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.
根据我们目前的认识，人类白细胞抗原（HLA）-B1502与亚洲人群中卡马西平（CBZ）诱发的史蒂文斯-约翰逊综合征及中毒性表皮坏死松解症（SJS/TEN）之间的关联十分明确。然而，其他HLA - B等位基因与CBZ诱发的严重皮肤不良反应（SCADR）之间的关系仍不明确。我们旨在通过荟萃分析确定CBZ诱发的SCADR患者中除HLA - B1502之外的其他等位基因。
使用Embase、PubMed、Web of Knowledge和Cochrane数据库进行全面的文献检索。从这些数据库建立之初至20xx年5月31日进行荟萃分析。检索调查HLA - B等位基因与CBZ诱发的SJS/TEN之间关联的研究。两名审阅者独立提取数据。使用RevMan 5.3软件计算总体比值比（OR）及相应的95%置信区间（CI）。
共有11项研究符合纳入标准，总计343例CBZ诱发的SJS/TEN病例、838例CBZ耐受对照及978例群体对照。我们观察到HLA - B1511是一个风险标志物，而HLA - B4001和HLA - B4601是服用CBZ患者发生SJS/TEN的保护标志物。在耐受组（OR = 17.43；95%CI = 3.12 - 97.41；P = 0.001）和群体对照组（OR = 11.11；95%CI = 2.62 - 47.09；P = 0.001）中，SJS/TEN病例均与HLA - B1511显著相关。敏感性分析发现，HLA - B*5801在东南亚人群中是一个保护标志物（OR = 0.23；95%CI = 0.09 - 0.58；P = 0.002）。
我们的研究表明，在亚洲人群中，HLA - B4001、HLA - B4601、HLA - B5801是CBZ诱发SJS/TEN发生的强有力保护因素，而HLA - B1511是一个风险因素。虽然可能需要更多研究来证实这些发现，但在开始CBZ治疗前，应考虑对亚洲患者进行风险等位基因检测。
