An interventional study of HLA screening before commencing aromatic AEDs in Epilepsy, Neuropathy and Psychiatric Illness, sponsored by Second Affiliated Hospital of Guangzhou Medical University. Status unknown at 1 site in China. Per ClinicalTrials.gov, last updated 2018-09-05.
Sponsored by Second Affiliated Hospital of Guangzhou Medical University · Not applicable, Interventional, and Prevention
Cutaneous adverse drug reactions (cADRs) include mild maculopapular exanthema (MPE) and severe cutaneous reactions such as hypersensitivity syndrome, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). cADRs are considered as a major public health issue because of their potentially life-threatening morbidity, especially severe cutaneous reactions. The incidence of SJS/TEN is estimated to vary from 1 in 1,000 to 10,000 drug exposures, and its mortality is as high as 35%. Antiepileptic drugs (AEDs), particularly those with aromatic ring structures such as carbamazepine (CBZ), oxcarbazepine (OXC), lamotrigine (LTG), phenobarbital (PB), and phenytoin (PHT), are among the most common causes of severe cutaneous reactions. The incidence of AED-induced SJS was estimated as 0.2% and all cases occurred in individuals receiving aromatic AEDs.
Previous studies have validated that the human leukocyte antigen (HLA) allele HLA-B*15:02 is strongly associated with CBZ-induced SJS/TEN in southern Han Chinese and populations in southeast Asia. Our recent studies indicated that HLA-A*24:02 is a common genetic risk factor for CBZ-, LTG-, and PHT-induced SJS/TEN. It is also associated with MPE. Additionally, another four alleles, including HLA-B*15:01, HLA-B*15:11, HLA-A*02:01,and HLA-DRB1*01:01, were showed to be potential risk factors for aromatic AEDs-induced SJS/TEN. In 2007, the US Food and Drug Administration issued the safety alert that recommended HLA-B*15:02 screening for people with Asian ancestry before starting CBZ, and avoidance of the drug if the test is positive. Subsequent studies from Taiwan, Hong Kong and Thailand demonstrated that HLA-B*15:02 screening before commencing CBZ can significantly reduce the incidence of CBZ-induced SJS/TEN. However, the overall incidence of AEDs-induced SJS/TEN remained unchanged in Hong Kong, as PHT-induced SJS/TEN increased when CBZ-SJS/TEN decreased. Moreover, no study focuses on the incidences of AEDs-induced cADRs with and without HLA screening before commencing aromatic AEDs. Therefore, we are planning to conduct a multicenter prospective study to examine the reduction of AEDs-induced cADRs after the HLA screening prior to the beginning of aromatic AEDs administration.
In this prospective study, 4000 or more patients from multicenters in southern China will be recruited. A HLA screening will be conducted before these patients start aromatic AEDs treatments. According to the HLA genotype, these patients will be divided into four groups that are three positive groups with different risk alleles and one negative group with no known risk allele. Aromatic AEDs were avoided or administrated with caution according to the risk level in the three positive groups, while they can be prescribed in the negative group. The effectiveness of HLA screening prior to the beginning of aromatic AEDs administration will be observed by the reduction of overall incidence of AEDs-induced cADRs.
Exclusion Criteria:
When HLA screening before commencing aromatic AEDs shows positive for both HLA-A\*24:02 and HLA-B\*15:02 in a patient, aromatic AEDs were not administrated for this patient.
Diagnostic Test: HLA screening before commencing aromatic AEDs
When HLA screening before commencing aromatic AEDs shows positive for HLA-B\*15:02, carbamazepine (CBZ) was not administrated, and other aromatic AEDs were prescribed with caution or avoided if alternative non-aromatic AEDs can be prescribed instead. When HLA screening before commencing aromatic AEDs shows positive for HLA-B\*15:01 or HLA-A\*24:02, aromatic AEDs were prescribed with caution or avoided if alternative non-aromatic AEDs can be prescribed instead.
Diagnostic Test: HLA screening before commencing aromatic AEDs
When HLA screening before commencing aromatic AEDs shows positive for any potential risk allele such as HLA-B\*15:11, HLA-A\*02:01and HLA-DRB1\*01:01, aromatic AEDs were prescribed with caution or avoided if alternative non-aromatic AEDs can be prescribed instead.
Diagnostic Test: HLA screening before commencing aromatic AEDs
When HLA screening before commencing aromatic AEDs shows negative for any known HLA risk allele , aromatic AEDs was administrated to these patients.
Diagnostic Test: HLA screening before commencing aromatic AEDs
When the risk HLA alleles are tested positive for the patients, aromatic AEDs were avoided or administrated with caution according to the risk level.
AEDs-induced cADRs incidence
the incidence of AEDs-induced cADRs within the first 3 months of commencing an aromatic AED
Time frame: 3 months
Plan to share: Yes — The clinical data and HLA genotype of the participant will be shared in the collaborators
Supporting information: Study protocol, Sap, Csr
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Second Affiliated Hospital of Guangzhou Medical University