Avoiding severe drug hypersensitivity reactions: a case for HLA genotyping for at‐risk patients

Helen Y Sun, Yaron Gu and Deshan F Sebaratnam
Med J Aust 2023; 219 (6): . || doi: 10.5694/mja2.52065
Published online: 18 September 2023

To the Editor: We agree with Stojanova and colleagues,1 who advocate for human leucocyte antigen (HLA) genotyping to prevent severe cutaneous adverse reactions from certain medications, such as abacavir and carbamazepine. In Australia, prospective HLA‐B*57:01 testing is rebated by the Medical Benefits Schedule (MBS) before commencement of abacavir. However, similar subsidisation does not exist for testing of other alleles, such as HLA‐B*15:02, before carbamazepine prescription. Carbamazepine is a well recognised trigger of Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) in people with the HLA‐B*15:02 allele. SJS/TEN are associated with great cost to the health care system, not only from the intensive multidisciplinary inpatient care associated with an acute episode but for long term morbidity involving both physical and psychological sequelae as well as loss of productivity. In the United States, the mean hospitalisation cost for TEN is in excess of $50 000.2 Subsidisation of HLA testing is likely to help to minimise the incidence of carbamazepine‐induced SJS/TEN, but decisions regarding outlay of health care resources also need to be tempered with a consideration of cost‐effectiveness. About 17% of the Australian population reported Asian ancestry1 and up to 18% of this population are carriers of HLA‐B*15:02. It therefore stands to reason that screening for SJS/TEN in Australia, particularly in high risk patients, before the commencement of carbamazepine is likely to be cost‐effective.3 Stojanova and colleagues1 attribute the lack of an MBS rebate for carbamazepine‐HLA‐B*15:02 screening to cost–benefit aspects at a population level, which include its lower positive predictive value and the higher number needed to test relative to abacavir‐HLA‐B*57:01. Despite this, carbamazepine‐HLA‐B*15:02 screening in high risk ancestries has proven to be cost‐effective in multicultural societies such as the United States4 and is recommended by both the US Food and Drug Administration and United Kingdom Medicines and Healthcare products Regulatory Agency.5 Because international cost‐efficacy studies lack external validity for application in the Australian setting, a cost‐effectiveness analysis using Australian inputs should be performed to determine if carbamazepine‐HLA‐B*15:02 screening is cost‐effective in high risk patients. If cost‐efficacy is determined, MBS rebates for HLA testing should extend to HLA‐B*15:02, bringing Australian pharmacogenetic screening policy on par with international standards.

  • 1 University of New South Wales, Sydney, NSW
  • 2 Liverpool Hospital, Sydney, NSW


The authors are grateful to the University of New South Wales (UNSW) School of Clinical Medicine for their support of Yaron Gu through the UNSW Honours Research Support Bursary.

Competing interests:

No relevant disclosures.

  • 1. Stojanova J, Day RO, Suthers G. Avoiding severe drug hypersensitivity reactions: a case for HLA genotyping for at‐risk patients. Med J Aust 2023; 219: 441‐444.‐severe‐drug‐hypersensitivity‐reactions‐case‐hla‐genotyping‐risk
  • 2. Hsu DY, Brieva J, Silverberg NB, Silverberg JI. Morbidity and mortality of stevens‐johnson syndrome and toxic epidermal necrolysis in United States adults. J Invest Dermatol 2016; 136: 1387‐1397.
  • 3. Kim E, McCrossin I, Frew JW. HLA‐B*1502 haplotype screening prior to carbamazepine administration in individuals of south‐east Asian ancestry nears cost‐effectiveness in preventing severe cutaneous adverse drug reactions. Australas J Dermatol 2018; 59: 245‐246.
  • 4. Choi H, Mohit B. Cost‐effectiveness of screening for HLA‐B*1502 prior to initiation of carbamazepine in epilepsy patients of Asian ancestry in the United States. Epilepsia 2019; 60: 1472‐1481.
  • 5. Chen Z, Liew D, Kwan P. Real‐world efficiency of pharmacogenetic screening for carbamazepine‐induced severe cutaneous adverse reactions. PLoS One 2014; 9: e96990.


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