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Susceptibility Genes and HLA for Cold Medicine-Related SJS/TEN with SOC

ABSTRACT: We investigated the genetic predisposition for the pathogenesis of Stevens–Johnson syndrome/epidermal necrolysis with severe ocular complications (SJS/TEN with SOC). Cold medicines (CMs) including multi-ingredient cold-medications and non-steroidal anti-inflammatory drugs (NSAIDs) were implicated in the development of SJS/TEN with SOC. Studies on the association between HLA genotypes and CM-related SJS/TEN with SOC (CM-SJS/TEN with SOC) revealed an association with HLA-A*02:06 in the Japanese; it may be a marker in Koreans. HLA-B*44:03 was associated with the Japanese, Thais, and Indians; in Brazilians of European ancestry, it may be a positive marker. PTGER3 is a susceptibility gene; HLA-A*02:06 and PTGER3 polymorphisms exerted additive effects in Japanese and Korean patients. A genome-wide association study showed that IKZF1 was associated with the Japanese. A meta-analysis including Japanese, Koreans, Indians, and Brazilians also revealed an association between CM-SJS/TEN with SOC and IKZF1. The upregulation of hsa-miR-628-3p in the plasma of SJS/TEN with SOC patients may suppress the expression of TLR3 and innate immune-related genes. Not only CMs but also the interaction of TLR3, PTGER3, IKZF1, and HLA and maybe some microbial infections are necessary for the onset of SJS/TEN with SOC.

SUBMITTER: Ueta M

PROVIDER: S-EPMC9309426 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundStevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), caused by allopurinol therapy, are strongly associated with the human leukocyte antigen (HLA), HLA-B*5801. Identification of HLA-B*5801 genotype before prescribing allopurinol offers the possibility of avoiding allopurinol-induced SJS/TEN. As there is a paucity of evidence about economic value of such testing, this study aims to determine the cost-effectiveness of HLA-B*5801 testing compared with usual care (no genetic testing) before allopurinol administration in Thailand.Methods and findingA decision analytical and Markov model was used to estimate life time costs and outcomes represented as quality adjusted life years (QALYs) gained. The model was populated with relevant information of the association between gene and allopurinol-induced SJS/TEN, test characteristics, costs, and epidemiologic data for Thailand from a societal perspective. Input data were obtained from the literature and a retrospective database analysis. The results were expressed as incremental cost per QALY gained. A base-case analysis was performed for patients at age 30. A series of sensitivity analyses including scenario, one-way, and probabilistic sensitivity analyses were constructed to explore the robustness of the findings. Based on a hypothetical cohort of 1,000 patients, the incremental total cost was 923,919 THB (USD 29,804) and incremental QALY was 5.89 with an ICER of 156,937.04 THB (USD 5,062) per QALY gained. The cost of gout management, incidence of SJS/TEN, case fatality rate of SJS/TEN, and cost of genetic testing are considered very influential parameters on the cost-effectiveness value of HLA-B*5801 testing.ConclusionsThe genetic testing for HLA-B*5801 before allopurinol administration is considered a highly potential cost-effective intervention in Thailand. The findings are sensitive to a number of factors. In addition to cost-effectiveness findings, consideration of other factors including ethical, legal, and social implications is needed for an informed policy decision making.

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Susceptibility Genes and HLA for Cold Medicine-Related SJS/TEN with SOC

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