Economic evaluation of HLA-B*15:02 screening for carbamazepine-induced severe adverse drug reactions in Thailand

Abstract

Purpose: There is strong evidence of an association between the presence of the human leukocyte antigen (HLA)-B*15:02 and two severe adverse drug reactions-Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)-in patients taking carbamazepine (CBZ), a common treatment for patients with epilepsy and neuropathic pain. As a result, there are calls for all patients that are due to undergo CBZ therapy to be screened for this genetic marker before commencing their therapy. This study aims to determine the value for money of HLA-B*15:02 screening compared to the following: (1) administering CBZ therapy without conducting patient screening, and (2) not prescribing CBZ but alternative drugs that are less likely to result in severe reactions, but that come at a higher cost.

Method: An economic evaluation was carried out by using a decision tree and Markov models to examine the cost-utility of providing HLA-B*15:02 screening for all patients with either newly diagnosed epilepsy or neuropathic pain in the Thai setting. All transitional probabilities were derived from the national and international literature. The majority of the data on direct medical care costs were collected from 10 community, provincial, and regional hospitals throughout Thailand. Direct non-medical cost and health-related quality of life (HRQoL) data were obtained from interviews that were conducted with 33 patients, some of whom had experienced severe drug reactions.

Key findings: The incremental cost-effectiveness ratio (ICER) of adopting a universal HLA-B*15:02 screening policy was estimated at 222,000 Thai baht, THB/quality-adjusted life year (QALY) gained for epilepsy patients and 130,000 THB/QALY gained for patients with neuropathic pain. Furthermore, we found that 343 patients need to be tested for HLA-B*15:02 allele to prevent one case of SJS/TEN.

Significance: Universal HLA-B*15:02 screening represents good value for the money in terms of preventing SJS/TEN in CBZ-treated patients with neuropathic pain at the Thai ceiling ratio of 120,000 THB/QALY gained. However, the prevalence of CBZ-induced SJS/TEN in the Thai population and the positive predictive value (PPV) are major factors that influence the cost-effectiveness of HLA-B*15:02 screening. Therefore, an active surveillance system to make a more accurate assessment of the prevalence CBZ-induced SJS/TEN in the Thai population would enhance the generalizability of the results.

Keywords: Cost-utility analysis; HLA-B*15:02; Stevens-Johnson syndrome; Toxic epidermal necrolysis.