Evaluation of Prospective<i>HLA-B*13:01</i>Screening to Prevent Dapsone Hypersensitivity Syndrome in Patients With Leprosy
Authors: Hong Liu, Zhenzhen Wang, Fangfang Bao, Chuan Wang, Lele Sun, Huimin Zhang, Gongqi Yu, Zihao Mi, Jianke Li, Lulu Li, Qing Zhao, Zhenhua Yue, Wei Zhao, Wenjun Yu, Jing Cao, Fei Xiong, Yaru Wang, Zemin Chai, Xiujun Cheng, Yuan Zhang, Fanghui Fu, Xiaoqiao Lang, Xiaoling Wang, Astrid Irwanto, Hana Krismawati, Xi’an Fu, Yonghu Sun, Jiabao You, Jian Liu, Qing Pan, Tongsheng Chu, Dianchang Liu, Shumin Chen, Jianping Shen, Liangbin Yan, Guocheng Zhang, Jianjun Liu, Furen Zhang, Li Xiong, Jun Yang, Jinlan Li, Wei Ke, Ming Li, Yong Ning, Junhao Xiong, Ming Li, Mingzhou Xiong, Bin Yang, Qizhi Duan, Hong Wang, Wei Li, Yanfei Kuang, Junhua Li, Lamei Wang, Qiuyang Cao, Peng Xiao, Bangzhong Xiao, Lianhua Zhang, Zhaoxing Lin, Yaofei Wang, Yunliang Shen, Liying Yan, Wenbin Wu, Hu Zheng, Xianfa Zhan, Wanghua Li, Xiujian Shang, Yujun Xu, Qiao Liu
Journal: JAMA Dermatology (2019)

Dapsone hypersensitivity syndrome (DHS) is the most serious adverse reaction associated with dapsone administration and one of the major causes of death in patients with leprosy, whose standard treatment includes multidrug therapy (MDT) with dapsone, rifampicin, and clofazimine. Although the HLA-B*13:01 polymorphism has been identified as the genetic determinant of DHS in the Chinese population, no studies to date have been done to evaluate whether prospective HLA-B*13:01 screening could prevent DHS by identifying patients who should not receive dapsone.To evaluate the clinical use of prospective HLA-B*13:01 screening for reduction of the incidence of DHS by excluding dapsone from the treatment for patients with HLA-B*13:01-positive leprosy.A prospective cohort study was conducted from February 15, 2015, to April 30, 2018, in 21 provinces throughout China. A total of 1539 patients with newly diagnosed leprosy were enrolled who had not received dapsone previously. After excluding patients who had a history of allergy to sulfones or glucose-6-phosphate dehydrogenase deficiency, 1512 individuals underwent HLA-B*13:01 genotyping. All of the patients were followed up weekly for the first 8 weeks after treatment to monitor for adverse events.Patients who were HLA-B*13:01 carriers were instructed to eliminate dapsone from their treatment regimens, and noncarrier patients received standard MDT.The primary outcome was the incidence of DHS. The historical incidence rate of DHS (1.0%) was used as a control.Among 1512 patients (1026 [67.9%] men, 486 [32.1%] women; mean [SD] age, 43.1 [16.2] years), 261 (17.3%) were identified as carriers of the HLA-B*13:01 allele. A total of 714 adverse events in 384 patients were observed during the follow-up period. Dapsone hypersensitivity syndrome did not develop in any of the 1251 patients who were HLA-B*13:01-negative who received dapsone, while approximately 13 patients would be expected to experience DHS, based on the historical incidence rate of 1.0% per year (P = 2.05 × 10-5). No significant correlation was found between other adverse events, including dermatologic or other events, and HLA-B*13:01 status.Prospective HLA-B*13:01 screening and subsequent elimination of dapsone from MDT for patients with HLA-B*13:01-positive leprosy may significantly reduce the incidence of DHS in the Chinese population.