Cost-effectiveness analysis of genotyping for HLA-B*15:02 in Indonesian patients with epilepsy using a generic model

Yuliwulandari, Rika; Shin, Jae Gook; Kristin, Erna; Suyatna, Fransiscus D.; Prahasto, Iwan Dwi; Prayuni, Kinasih; Mahasirimongkol, Surakameth; Cavallari, Larisa H.; Mitropoulou, Christina; Patrinos, George P.; Hao, Jing; Williams, Marc S.; Snyder, Susan

doi:10.1038/s41397-021-00225-9

Cited by 11 publications

(10 citation statements)

References 31 publications

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“…31 As such, a conservative estimate for valproate-induced SJS/TEN was derived from epidemiologic studies 32 and presented in Table 1. 12,20,21,[24][25][26][27][28][29][30][32][33][34][35][36][37][38][39][40][41][42][43] The probability of a patient developing carbamazepine-induced SJS/ TEN and subsequent valproate-induced SJS/TEN was assumed to be negligible. Patients were transitioned to treatment with levetiracetam if they were positive carriers of HLA-B*15:02 and subsequently did not benefit from valproate therapy.…”

Section: Epilepsy Treatmentmentioning

confidence: 99%

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Economic Evaluation of HLA-B*15:02 Genotyping for Asian Australian Patients With Epilepsy

Gu,

Shih,

Geevasinga

et al. 2024

JAMA Dermatol

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ImportanceThe HLA-B*15:02 allele has been associated with an increased risk of carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in specific Asian populations (including Han Chinese, Malaysian, Thai, and Vietnamese individuals). While HLA-B*15:02 genotype testing in Asian populations is recommended by several international prescribing guidelines, it is not subsidized by the Medicare Benefits Schedule in Australia.ObjectiveTo evaluate the cost-effectiveness of HLA-B*15:02 genotyping in Asian Australian patients with epilepsy.Design, Setting, and ParticipantsA model with components of decision analysis and Markov simulation was developed to simulate clinical trajectories of adult Asian Australian patients with newly diagnosed epilepsy being considered for carbamazepine treatment. Cost-effectiveness and cost-utility analyses over a lifetime time horizon were conducted from the perspective of the Australian health care sector. The study was conducted in May 2023 and data analysis was performed from August 2023 to November 2023.InterventionNo HLA-B*15:02 genotyping and the empirical initiation of treatment with carbamazepine vs HLA-B*15:02 genotyping and the initiation of treatment with valproate in allele carriers.Main Outcomes and MeasuresLife-years (LYs), quality-adjusted life-years (QALYs), and costs in 2023 Australian dollars (A$); incremental cost-effectiveness ratios.ResultsHLA-B*15:02 screening was associated with an additional mean cost of A$114 (95% CI, −A$83 to A$374; US$76; 95% CI, −US$55 to US$248) and a reduction in 0.0152 LYs (95% CI, 0.0045 to 0.0287 LYs) but improvement by 0.00722 QALYs (95% CI, −0.0247 to −0.01210) compared with no screening, resulting in an incremental cost-effectiveness ratio of A$15 839 per QALY gained (US$10 523 per QALY). Therefore, universal genotyping for Asian Australian individuals was cost-effective compared with current standards of practice at the A$50 000 per QALY willingness-to-pay threshold. Sensitivity analyses demonstrated that the intervention remained cost-effective across a range of costs, utilities, transition probabilities, and willingness-to-pay thresholds. At the A$50 000 per QALY willingness-to-pay threshold, universal screening was the preferred strategy in 88.60% of simulations.Conclusions and RelevanceThe results of this economic evaluation suggest that HLA-B*15:02 screening represents a cost-effective choice for Asian Australian patients with epilepsy who are being considered for treatment with carbamazepine.

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Section: Epilepsy Treatmentmentioning

confidence: 99%

“…As such, ethnicity-weighted positive and negative predictive values were calculated based on Australian Census data 45 and predictive values from prior literature. 12,[32][33][34][35] This provided a conservative estimate for a positive predictive value of 3.32%. A negative predictive value of 99.98% was also estimated (Table 1).…”

Section: Hla-b*15:02mentioning

confidence: 99%

Economic Evaluation of HLA-B*15:02 Genotyping for Asian Australian Patients With Epilepsy

Gu,

Shih,

Geevasinga

et al. 2024

JAMA Dermatol

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“…Carbamazepine (CBZ) is a drug widely used to treat epilepsy, bipolar disorder and trigeminal neuralgia [64,92,93]. While usually well-tolerated, up to 10% of patients may have a cutaneous ADR [93].…”

Section: Carbamazepine-induced Scarsmentioning

confidence: 99%

Genetic Determinants in HLA and Cytochrome P450 Genes in the Risk of Aromatic Antiepileptic-Induced Severe Cutaneous Adverse Reactions

Sukasem

Musa

Noor

et al. 2021

JPM

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Adverse drug reaction (ADR) is a pressing health problem, and one of the main reasons for treatment failure with antiepileptic drugs. This has become apparent in the event of severe cutaneous adverse reactions (SCARs), which can be life-threatening. In this review, four hypotheses were identified to describe how the immune system is triggered in the development of SCARs, which predominantly involve the human leukocyte antigen (HLA) proteins. Several genetic variations in HLA genes have been shown to be strongly associated with the susceptibility to developing SCARs when prescribed carbamazepine or phenytoin. These genetic variations were also shown to be prevalent in certain populations. Apart from the HLA genes, other genes proposed to affect the risk of SCARs are genes encoding for CYP450 drug-metabolising enzymes, which are involved in the pharmacokinetics of offending drugs. Genetic variants in CYP2C9 and CYPC19 enzymes were also suggested to modulate the risk of SCARs in some populations. This review summarizes the literature on the manifestation and aetiology of antiepileptic-induced SCARs, updates on pharmacogenetic markers associated with this reaction and the implementation of pre-emptive testing as a preventive strategy for SCARs.

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“…Previous studies assessing the cost-effectiveness of pharmacogenetic testing among patients with epilepsy have done so for single gene variants including HLA-B*1502 and HLA-A*3101. [5][6][7][8][9][10] These studies have evaluated the cost-effectiveness of screening for single gene variants among high-risk populations, for example, HLA-B*1502 among Asians who are at risk of severe side effects such as Stevens-Johnson syndrome and toxic epidermal necrolysis following carbamazepine exposure. 11 In the study by Gordon and colleagues, 2 the costeffectiveness analysis was based on panel sequencing, and sensitivity analysis was conducted using the cost of whole exome sequencing.…”

Section: Introductionmentioning

confidence: 99%

“…It is uncertain how costs and outcomes differ with other sequencing approaches such as whole genome sequencing. There are discrepant findings on the cost‐effectiveness of screening for HLA‐B*1502 in the literature, 6,7,9,10 likely related to variability in the frequency of HLA‐B*1502 in the population assessed 7 . Gordon and colleagues 2 examined the impact of variability in the prevalence of gene variants (ranging from .06 to .64) through sensitivity analysis, and showed that the prevalence of gene variants was not an influential factor and genetically guided therapy remained a cost‐effective strategy within the range of prevalence examined.…”

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confidence: 99%

Gene panel to guide antiseizure medication prescribing: Does the cost justify the benefits?

Widjaja

2022

Epilepsia

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Pharmacogenomics (also known as pharmacogenetics) is the study of how an individual's genetic variants influence drug responses, including the variants associated with adverse drug reactions and treatment efficacy. Genes encoding antiseizure medications (ASMs) metabolic enzymes, transporters, and carriers are important modulating factors of drug response, and account for interindividual differences in the efficacy and adverse reactions of ASMs. Pharmacogenomics hold the potential to identify variants associated with response to ASMs, and could therefore lead to personalized epilepsy treatment, with the promise of the right drug for the right patient. A previous study has identified 123 genes implicated in the metabolism, transport, and target pathways of six ASMs, including levetiracetam, sodium valproate, lamotrigine, carbamazepine, zonisamide, and perampanel. 1 However, the downstream effects of pharmacogenomics on decisions regarding personalized selection of ASMs and ultimately on patient outcomes are not fully understood. Microsimulation provides an opportunity to model the downstream effects

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Cost-effectiveness analysis of genotyping for HLA-B*15:02 in Indonesian patients with epilepsy using a generic model

Cited by 11 publications

References 31 publications

Economic Evaluation of HLA-B*15:02 Genotyping for Asian Australian Patients With Epilepsy

Economic Evaluation of HLA-B*15:02 Genotyping for Asian Australian Patients With Epilepsy

Genetic Determinants in HLA and Cytochrome P450 Genes in the Risk of Aromatic Antiepileptic-Induced Severe Cutaneous Adverse Reactions

Gene panel to guide antiseizure medication prescribing: Does the cost justify the benefits?

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