Literature Review

Genetic Screening May Reduce Carbamazepine-Induced Cutaneous Adverse Reactions

Data may enable a more consistent approach to the safe administration of a commonly prescribed therapy.


 

Preemptive HLA-A*31:01 genetic screening may significantly decrease the incidence of carbamazepine-induced cutaneous adverse reactions in Japanese patients, according to a report published online ahead of print April 2 in JAMA Neurology. According to the researchers, their finding suggests that such screening may be warranted in routine clinical practice.

Carbamazepine, which is widely used to treat seizures, neuropathic pain, and other disorders, is a common cause of cutaneous adverse drug reactions worldwide. The allele HLA-A*31:01 has been associated with carbamazepine-induced cutaneous drug reactions in Japanese and European populations. The clinical utility of HLA-A*31:01 screening, however, has not been evaluated.

Genetic Screening Informed Treatment

To assess the use of HLA-A*31:01 genetic screening to identify individuals at risk of carbamazepine-induced cutaneous drug reactions, researchers from the Genotype-Based Carbamazepine Therapy Study Group conducted a cohort study in 36 hospitals in Japan from January 2012 to November 2014. The investigators enrolled 1,202 patients who were eligible to receive carbamazepine during the study period. Preemptive HLA-A*31:01 screening was performed for 1,187 study participants. Patients who did not start treatment with carbamazepine or alternative drugs were excluded. Participants were interviewed once weekly for eight weeks to monitor the development of cutaneous adverse drug reactions.

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 the allele. The study’s main outcome was the incidence of carbamazepine-induced cutaneous adverse drug reactions.

Of the 1,130 patients who were prescribed carbamazepine or alternative drugs, the mean age was 37.4; 614 (54.3%) were men, and 198 (17.5%) were positive for HLA-A*31:01. Dermatologists identified 23 patients (2.0%) who had carbamazepine-induced cutaneous adverse drug reactions, of whom four patients required hospitalization. Drug-induced hypersensitivity syndrome was observed for three patients, maculopapular eruption for nine patients, erythema multiforme for five patients, and an undetermined type of cutaneous adverse drug reaction for six patients. No patient developed Stevens-Johnson syndrome or toxic epidermal necrolysis.

Comparison with a historical control indicated that the preemptive use of HLA-A*31:01 screening was associated with a 40% reduction in the incidence of carbamazepine-induced cutaneous adverse drug reactions.

Two Alleles

The researchers noted that the clinical utility of the HLA-B*15:02 genetic test for reducing carbamazepine-induced cutaneous drug reactions has already been established by preemptive screening. However, the frequency of the HLA-B*15:02 allele is low in Korean, Japanese, African, and European populations.

In contrast, the frequency of the HLA-A*31:01 allele is 7% to 9% in Japanese, 5% in Korean, 2% in Chinese, 2% to 3% in European, and 1% in African populations. Moreover, HLA-A*31:01 has been associated with a full spectrum of carbamazepine-induced cutaneous adverse drug reactions. Therefore, “HLA-A*31:01 genetic screening prior to prescribing carbamazepine would be useful for preventing many types of carbamazepine-induced cutaneous adverse drug reactions in a range of patient populations,” the researchers concluded.

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