TY - JOUR
T1 - Association of HLA-A*31:01 Screening with the incidence of carbamazepine-induced cutaneous adverse reactions in a Japanese population
AU - GENCAT Study Group
AU - Mushiroda, Taisei
AU - Takahashi, Yukitoshi
AU - Onuma, Teiichi
AU - Yamamoto, Yoshiaki
AU - Kamei, Tetsumasa
AU - Hoshida, Tohru
AU - Takeuchi, Katsuya
AU - Otsuka, Kotaro
AU - Okazaki, Mitsutoshi
AU - Watanabe, Masako
AU - Kanemoto, Kosuke
AU - Oshima, Tomohiro
AU - Watanabe, Atsushi
AU - Minami, Shiro
AU - Saito, Kayoko
AU - Tanii, Hisashi
AU - Shimo, Yasushi
AU - Hara, Minoru
AU - Saitoh, Shinji
AU - Kinoshita, Toshihiko
AU - Kato, Masaki
AU - Yamada, Naoto
AU - Akamatsu, Naoki
AU - Fukuchi, Toshihiko
AU - Ishida, Shigenobu
AU - Yasumoto, Shingo
AU - Takahashi, Atsushi
AU - Ozeki, Takeshi
AU - Furuta, Takahisa
AU - Saito, Yoshiro
AU - Izumida, Nobuyuki
AU - Kano, Yoko
AU - Shiohara, Tetsuo
AU - Kubo, Michiaki
AU - Shimo, Yasushi
AU - Watanabe, Atsushi
AU - Minami, Shiro
AU - Takeuchi, Katsuya
AU - Otsuka, Kotaro
AU - Kamei, Tetsumasa
AU - Kanemoto, Kosuke
AU - Kanemoto, Kosuke
AU - Fukuchi, Toshihiko
AU - Okazaki, Mitsutoshi
AU - Akamatsu, Naoki
AU - Kinoshita, Toshihiko
AU - Kinoshita, Toshihiko
AU - Onuma, Teiichi
AU - Hoshida, Tohru
AU - Ishida, Shigenobu
N1 - Publisher Copyright:
© 2018 American Medical Association. All rights reserved.
PY - 2018/7
Y1 - 2018/7
N2 - IMPORTANCE: Carbamazepine, a commonly used antiepileptic drug, is one of the most common causes of cutaneous adverse drug reactions (cADRs) worldwide. The allele HLA-A*31:01 is reportedly associated with carbamazepine-induced cADRs in Japanese and European populations; however, the clinical utility of HLA-A*31:01 has not been evaluated. OBJECTIVE: To assess the use of HLA-A*31:01 genetic screening to identify Japanese individuals at risk of carbamazepine-induced cADRs. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted across 36 hospitals in Japan from January 2012 to November 2014 among 1202 patients who had been deemed suitable to start treatment with carbamazepine. Preemptive HLA-A*31:01 genetic screening was performed for 1187 participants. Patients who did not start treatment with carbamazepine or alternative drugs were excluded. Participants were interviewed once weekly for 8 weeks to monitor the development of cADRs. Data analysis was performed from June 8, 2015, to December 27, 2016. EXPOSURES: Neuropsychiatrists were asked to prescribe carbamazepine for patients who tested negative for HLA-A*31:01 and alternative drugs for those who tested positive for HLA-A*31:01. MAIN OUTCOMES AND MEASURES: Incidence of carbamazepine-induced cADRs. RESULTS: Of the 1130 included patients who were prescribed carbamazepine or alternative drugs, the mean (range) age was 37.4 (0-95) years, 614 (54.3%) were men, and 198 (17.5%) were positive for HLA-A*31:01. Expert dermatologists identified 23 patients (2.0%) who had carbamazepine-induced cADRs, of which 4 patients required hospitalization. Drug-induced hypersensitivity syndrome was observed for 3 patients, maculopapular eruption for 9 patients, erythema multiforme for 5 patients, and an undetermined type of cADR for 6 patients. No patient developed Stevens-Johnson syndrome or toxic epidermal necrolysis. Compared with historical controls, the incidence of carbamazepine-induced cADRs was significantly decreased (for BioBank Japan data: incidence, 3.4%; odds ratio, 0.60; 95% CI, 0.36-1.00; P = .048; for the Japan Medical Data Centre claims database: incidence, 5.1%; odds ratio, 0.39; 95% CI, 0.26-0.59; P < .001). CONCLUSIONS AND RELEVANCE: Preemptive HLA-A*31:01 genetic screening significantly decreased the incidence of carbamazepine-induced cADRs among Japanese patients, which suggests that it may be warranted in routine clinical practice.
AB - IMPORTANCE: Carbamazepine, a commonly used antiepileptic drug, is one of the most common causes of cutaneous adverse drug reactions (cADRs) worldwide. The allele HLA-A*31:01 is reportedly associated with carbamazepine-induced cADRs in Japanese and European populations; however, the clinical utility of HLA-A*31:01 has not been evaluated. OBJECTIVE: To assess the use of HLA-A*31:01 genetic screening to identify Japanese individuals at risk of carbamazepine-induced cADRs. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted across 36 hospitals in Japan from January 2012 to November 2014 among 1202 patients who had been deemed suitable to start treatment with carbamazepine. Preemptive HLA-A*31:01 genetic screening was performed for 1187 participants. Patients who did not start treatment with carbamazepine or alternative drugs were excluded. Participants were interviewed once weekly for 8 weeks to monitor the development of cADRs. Data analysis was performed from June 8, 2015, to December 27, 2016. EXPOSURES: Neuropsychiatrists were asked to prescribe carbamazepine for patients who tested negative for HLA-A*31:01 and alternative drugs for those who tested positive for HLA-A*31:01. MAIN OUTCOMES AND MEASURES: Incidence of carbamazepine-induced cADRs. RESULTS: Of the 1130 included patients who were prescribed carbamazepine or alternative drugs, the mean (range) age was 37.4 (0-95) years, 614 (54.3%) were men, and 198 (17.5%) were positive for HLA-A*31:01. Expert dermatologists identified 23 patients (2.0%) who had carbamazepine-induced cADRs, of which 4 patients required hospitalization. Drug-induced hypersensitivity syndrome was observed for 3 patients, maculopapular eruption for 9 patients, erythema multiforme for 5 patients, and an undetermined type of cADR for 6 patients. No patient developed Stevens-Johnson syndrome or toxic epidermal necrolysis. Compared with historical controls, the incidence of carbamazepine-induced cADRs was significantly decreased (for BioBank Japan data: incidence, 3.4%; odds ratio, 0.60; 95% CI, 0.36-1.00; P = .048; for the Japan Medical Data Centre claims database: incidence, 5.1%; odds ratio, 0.39; 95% CI, 0.26-0.59; P < .001). CONCLUSIONS AND RELEVANCE: Preemptive HLA-A*31:01 genetic screening significantly decreased the incidence of carbamazepine-induced cADRs among Japanese patients, which suggests that it may be warranted in routine clinical practice.
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U2 - 10.1001/jamaneurol.2018.0278
DO - 10.1001/jamaneurol.2018.0278
M3 - Article
AN - SCOPUS:85050999952
SN - 2168-6149
VL - 75
SP - 842
EP - 849
JO - JAMA Neurology
JF - JAMA Neurology
IS - 7
ER -