Evaluation of ProspectiveHLA-B*13:01Screening to Prevent Dapsone Hypersensitivity Syndrome in Patients With Leprosy

Abstract

; and the Dapsone Hypersensitivity Syndrome Prevention Working Group IMPORTANCE 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. OBJECTIVE 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. DESIGN, SETTING, AND PARTICIPANTS 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. EXPOSURES Patients who were HLA-B*13:01 carriers were instructed to eliminate dapsone from their treatment regimens, and noncarrier patients received standard MDT. MAIN OUTCOMES AND MEASURES The primary outcome was the incidence of DHS. The historical incidence rate of DHS (1.0%) was used as a control. RESULTS 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. CONCLUSIONS AND RELEVANCE 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.

Validation study of HLA-B*13:01 as a biomarker of dapsone hypersensitivity syndrome in leprosy patients in Indonesia

“…The results have been independently validated in various Asian populations including Thais[ 15 ], Koreans[ 16 ], Indians[ 17 ] and Taiwanese[ 18 ]. Screening for this allele in new leprosy patients before the initiation of MDT has proven beneficial to reduce incidence rate of DHS in China to zero[ 19 ].…”

Genetic variants associated with T cell–mediated cutaneous adverse drug reactions: A PRISMA‐compliant systematic review—An EAACI position paper

“…Furthermore, DPS‐specific cytotoxic T cells were significantly activated when cocultured with HLA‐B*13:01 ‐expressing antigen‐presenting cells in the presence of DPS . A prospective study demonstrated that HLA‐B*13:01 screening and DPS elimination from multidrug therapy for treating leprosy for patients harboring the HLA‐B*13:01 allele was an effective strategy for reducing the incidence of DIHS in the Chinese population …”

Utility evaluation of HLA-B*13:01 screening in preventing trichloroethylene-induced hypersensitivity syndrome in a prospective cohort study

“…The frequency of this allele in southern Chinese (10.47%) is higher than that in northern Chinese (5.85%), which might be the reason for high TIHS incidence found in southern China, especially in Guangdong Province. Across the world, HLA-B*13:01 is rare in Caucasian and African, but has a higher frequency in Asian population 23. The association between HLA-B*13:01 and TIHS has been observed in Japanese 7.…”