Rate of Carbamazepine-Induced Cutaneous Adverse Reactions Reduced With Genetic Screening

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Carbamazepine, an anticonvulsant agent used for seizure control in patients with epilepsy, is known to be associated with cutaneous adverse reactions.
Carbamazepine, an anticonvulsant agent used for seizure control in patients with epilepsy, is known to be associated with cutaneous adverse reactions.

Preemptive genetic screening for the allele HLA-A*31:01 prior to prescribing carbamazepine  was found to be associated with a 40% reduction in the incidence of cutaneous adverse drug reactions (cADRs) in a Japanese population compared with historical controls, according to the results of a cohort study conducted in 36 hospitals across Japan and published in JAMA Neurology.1

Investigators sought to evaluate the use of HLA-A*31:01 genetic screening to identify Japanese individuals who are at risk for carbamazepine-induced cADRs. The study was performed from January 2012 to November 2014 and included 1202 patients considered suitable for initiating carbamazepine therapy. Preemptive HLA-A*31:01 genetic screening was carried out in 1187 individuals. All participants were interviewed once weekly for 8 weeks to monitor the development of cADRs. Data were analyzed from June 8, 2015, through December 27, 2016.

Neuropsychiatrists were requested to prescribe carbamazepine for patients who tested negative for HLA-A*31:01 and an alternative agent for those who tested positive for
HLA-A*31:01. The main study outcome was the incidence of carbamazepine-induced cADRs.

A total of 1130 patients were prescribed carbamazepine or an alternative medication. Mean patient age was 37.4 years; 54.3% (614 of 1130) were men, and 17.5% (198 of 1130) tested positive for HLA-A*31:01. Definite or probable carbamazepine-induced cADRs were identified in 2.0% (23 of 1130) of participants, with 4 of these patients requiring hospitalization. Adverse reactions included drug-induced hypersensitivity syndrome (n=3), maculopapular eruption (n=9), and erythema multiforme (n=5); an undetermined type of CADR was identified in 6 patients.

The 2.0% rate of carbamazepine-induced cADRs reported in this study reflected a 40% decrease compared with the incidence reported in a historical control group (P <.001). The current study “provides initial data that preemptive strategies may allow for a more consistent approach to safely administer this commonly used medication” [carbamazepine].2

The investigators concluded that although cost-effectiveness analyses are required, the use of preemptive HLA-A*31:01 genetic screening to decrease the rate of carbamazepine-induced cADRs in routine clinical practice seems to be warranted.

References

  1. Mushiroda T, Takahashi Y, Onuma T, et al; for the GENCAT Study Group. Association of HLA-A*31:01 screening with the incidence of carbamazepine-induced cutaneous adverse reactions in a Japanese population [published online April 2, 2018]. JAMA Neurol. doi:10.1001/jamaneurol.2018.0278
  2. He Y, Seminario-Vidal L, McLeod H. Avoidance of severe cutaneous adverse drug events as a first step in precision neurology [published online April 2, 2018]. JAMA Neurol. doi:10.1001/jamaneurol.2018.0001

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