Association of genetic factors and non-genetic factors with Carbamazepine-induced cutaneous adverse drug reactions in Thai patients

Abstract

Background: Carbamazepine (CBZ) is a drug with an important role in treatment of epilepsy, neuropathic pain and bipolar disorders. However, CBZ-induced cutaneous adverse drug reactions (cADRs) is a major problem for the use of this drug. It is well known that patients with HLA-B*15:02 allele have the significant risk for severe cADRs i.e. Stevens Johnson syndrome (SJS/TEN) and toxic epidermal necrolysis (TEN). The association of other alleles and CBZ-induced SJS/TEN or maculopapular eruption (MPE) are not clear in Thai population due to the lack of studies and low incidences of such cADRs. Objective: To investigate the association of HLA class I including non-genetic factors with carbamazepine-induced SJS/TEN or MPE in Thai patient. Methods: This was a retrospective case-control study in Thai patients who had previously received carbamazepine at Neurological Institute of Thailand during 2007-2017. The total of study groups consisted of 89 participants, including 16 patients with SJS/TEN, 22 patients with MPE, and 51 patients as CBZ-tolerant control. The medical records were reviewed and genetic markers were analyzed. Result: There were association between HLA-B*15:02 and HLA-A*02:03 and carbamazepine-induced SJS/TEN was observed (OR=14; p <0.001; 95%CI, 3.66-53.53 and OR=5.46; p=0.022; 95%CI, 1.30-22.80, respectively). HLA-B* 51:01 was shown to be associated with CBZ-induced MPE (OR=4.71; p=0.049; 95%CI, 1.01-21.83). No no-genetic factors including age, dose, concurrent potential interacting drugs and history of drug allergy are associated with CBZ-induced cADRs.Conclusion: This study demonstrated that the HLA class I gene was associated with SJS/TEN and MPE rash from carbamazepine. The assoication of non-genetic factors cannot be concluded from this study because it needs to be answered in future studies with more power.