Association of HLA-A*31:01 Screening With the Incidence of Carbamazepine-Induced Cutaneous Adverse Reactions in a Japanese Population.
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| 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.
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| Authors | Taisei Mushiroda, Yukitoshi Takahashi, Teiichi Onuma, Yoshiaki Yamamoto, Tetsumasa Kamei, Tohru Hoshida, Katsuya Takeuchi, Kotaro Otsuka, Mitsutoshi Okazaki, Masako Watanabe, Kosuke Kanemoto, Tomohiro Oshima, Atsushi Watanabe, Shiro Minami, Kayoko Saito, Hisashi Tanii, Yasushi Shimo, Minoru Hara, Shinji Saitoh, Toshihiko Kinoshita, Masaki Kato, Naoto Yamada, Naoki Akamatsu, Toshihiko Fukuchi, Shigenobu Ishida, Shingo Yasumoto, Atsushi Takahashi, Takeshi Ozeki, Takahisa Furuta, Yoshiro Saito, Nobuyuki Izumida, Yoko Kano, Tetsuo Shiohara, Michiaki Kubo, GENCAT Study Group |
| Journal | JAMA neurology (JAMA Neurol) Vol. 75 Issue 7 Pg. 842-849 (07 01 2018) ISSN: 2168-6157 [Electronic] United States |
| PMID | 29610831 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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