Usage Pattern of Carbamazepine and Associated Severe Cutaneous Adverse Reactions in Singapore Following Implementation of HLA-B*15:02 Genotyping as Standard-of-Care

Abstract

jointly issued recommendations for HLA-B*15:02 genotyping before starting carbamazepine (CBZ) in new patients of Asian ancestry as standard of care. The Ministry of Health also approved a 75% subsidy for HLA-B*15:02 genotyping to all patients on subsidy at public healthcare institutions. To understand the impact of these regulatory decisions, we researched the usage patterns for CBZ and levetiracetam, the trend of Stevens-Johnson syndrome/toxic epidermal necrolysis [Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)] reports associated with antiepileptic drugs and the take-up rates of HLA-B*15:02 tests in Singapore. In the 5-year post-policy period, we found that the annual number of reported SJS/TEN cases associated with all antiepileptic drugs was significantly decreased by 57% (p = 0.015); SJS/TEN cases associated with CBZ and phenytoin reduced by 92% and 42% respectively. New CBZ users decreased by 31% while new levetiracetam users approximately doubled. The annual number of HLA-B*15:02 tests conducted increased from 444 to approximately 1,200. Regulatory recommendations for HLA-B*15:02 genotyping as standard of care coupled with government subsidy for the test had contributed to a reduction in CBZ SJS/TEN in Singapore by >90%, in line with that observed in other Asian countries with similar policies. Additionally, the number of phenytoin-SJS/TEN cases also declined. Taken together, this represents a successful example of precision medicine through implementation of a genotyping program to reduce a rare but serious adverse drug reaction among at-risk individuals, while preserving the availability of an effective and low-cost medicine for the broader population.

Awareness of HLA‐B* 15:02 screening in trigeminal neuralgia and the gene screening policy among dentists in Southern Thailand

“…Although these policies have successfully decreased the incidence of SJS/TEN, clinicians often prefer to prescribe other anti-epileptic drugs (AEDs) that do not require gene screening. 17,18 Thailand implemented a policy for HLA-B* 15:02 gene screening in 2018. The Ministry of Public Health (MOPH) suggested healthcare professionals must perform gene screening prior to commencing CBZ in order to decrease SJS/TEN events among the Thai population.…”

Lamotrigine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Singapore: A case series

“…6 The validation of the association of HLA-B*1502 allele with carbamazepine-induced SCAR led to the Ministry of Health's implementation and subsidy of HLA-B*1502 testing in 2013 as the standard-of-care prior to the initiation of carbamazepine, which contributed to a reduction in carbamazepine-induced SJS/TEN in Singapore by 92%. 7 In our case series (Table 1), there was no specific HLA allele that was demonstrated to be carried by the majority of patients (defined as greater than 50%). Half of the patients were found to carry HLA-DRB1*1202.…”

GenotypingHLAalleles to predict the development of Severe cutaneous adverse drug reactions (SCARs): state-of-the-art

“…The UC scheme, operated by the National Health Security Office (NHSO), has the coverage for HLA-B*15:02 screening with a reimbursement of 28 USD per person in Thailand [98]. HLA-B*15:02 testing is mandatory in Taiwan and Hong Kong and is highly recommended as standard of care in Singapore before initiation of carbamazepine therapy [104,105]. The reimbursement for the HLA-B*58:01 screening test is likely to include within the UC by 2021 in Thailand.…”