Association of HLA-A*31:01 Screening with the incidence of carbamazepine-induced cutaneous adverse reactions in a Japanese population

GENCAT Study Group

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)842-849
Number of pages8
JournalJAMA Neurology
Volume75
Issue number7
DOIs
Publication statusPublished - 01-07-2018

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Carbamazepine
Drug-Related Side Effects and Adverse Reactions
Skin
Incidence
Population
Genetic Testing
Japan
HLA-A31 antigen
Drug Hypersensitivity Syndrome
Odds Ratio
Pharmaceutical Preparations
Erythema Multiforme
Stevens-Johnson Syndrome
Anticonvulsants
Hospitalization
Cohort Studies
Alleles
Outcome Assessment (Health Care)
Databases

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

Cite this

@article{7195ae8b6c3144a1b3b0b3f8c293d266,
title = "Association of HLA-A*31:01 Screening with the incidence of carbamazepine-induced cutaneous adverse reactions in a Japanese population",
abstract = "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.",
author = "{GENCAT Study Group} and Taisei Mushiroda and Yukitoshi Takahashi and Teiichi Onuma and Yoshiaki Yamamoto and Tetsumasa Kamei and Tohru Hoshida and Katsuya Takeuchi and Kotaro Otsuka and Mitsutoshi Okazaki and Masako Watanabe and Kosuke Kanemoto and Tomohiro Oshima and Atsushi Watanabe and Shiro Minami and Kayoko Saito and Hisashi Tanii and Yasushi Shimo and Minoru Hara and Shinji Saitoh and Toshihiko Kinoshita and Masaki Kato and Naoto Yamada and Naoki Akamatsu and Toshihiko Fukuchi and Shigenobu Ishida and Shingo Yasumoto and Atsushi Takahashi and Takeshi Ozeki and Takahisa Furuta and Yoshiro Saito and Nobuyuki Izumida and Yoko Kano and Tetsuo Shiohara and Michiaki Kubo and Yasushi Shimo and Atsushi Watanabe and Shiro Minami and Katsuya Takeuchi and Kotaro Otsuka and Tetsumasa Kamei and Michiaki Kubo and Kayoko Saito and Kosuke Kanemoto and Kosuke Kanemoto and Toshihiko Fukuchi and Mitsutoshi Okazaki and Shinji Saitoh and Naoki Akamatsu and Toshihiko Kinoshita and Toshihiko Kinoshita",
year = "2018",
month = "7",
day = "1",
doi = "10.1001/jamaneurol.2018.0278",
language = "English",
volume = "75",
pages = "842--849",
journal = "JAMA Neurology",
issn = "2168-6149",
publisher = "American Medical Association",
number = "7",

}

Association of HLA-A*31:01 Screening with the incidence of carbamazepine-induced cutaneous adverse reactions in a Japanese population. / GENCAT Study Group.

In: JAMA Neurology, Vol. 75, No. 7, 01.07.2018, p. 842-849.

Research output: Contribution to journalArticle

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 - Kubo, Michiaki

AU - Saito, Kayoko

AU - Kanemoto, Kosuke

AU - Kanemoto, Kosuke

AU - Fukuchi, Toshihiko

AU - Okazaki, Mitsutoshi

AU - Saitoh, Shinji

AU - Akamatsu, Naoki

AU - Kinoshita, Toshihiko

AU - Kinoshita, Toshihiko

PY - 2018/7/1

Y1 - 2018/7/1

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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