Cost-effectiveness of HLA-B*1502 genotyping in adult patients with newly diagnosed epilepsy in Singapore
ABSTRACT Asians who carry the HLA-B*1502 allele have an elevated risk of developing Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) when treated with the antiepileptic drugs (AEDs) carbamazepine (CBZ) and phenytoin (PHT). With a focus on Singapore, this analysis identifies circumstances in which genotyping and targeted treatment with alternative AEDs that do not induce SJS/TEN is likely to be more cost-effective than 1) treatment with CBZ or PHT without genotyping or 2) providing a more expensive drug that does not induce SJS/TEN to all patients without genotyping.
A decision tree model was developed in TreeAge. The model takes into account costs of epilepsy treatments and genotyping, reductions in quality of life and increased costs resulting from SJS/TEN complications, the prevalence of the risk allele, the positive predictive value (PPV) of genotyping, life expectancy, and other factors.
Compared with no genotyping and providing CBZ to all, genotyping results in an incremental cost-effectiveness ratio of $37,030/quality-adjusted life year (QALY) for Chinese patients, $7,930/QALY for Malays, and $136,630/QALY for Indians in Singapore.
Because of the different population allele frequencies of HLA-B*1502 among different ethnic groups, genotyping for HLA-B*1502 and providing alternate AEDs to those who test positive is cost-effective for Singaporean Chinese and Malays, but not for Singaporean Indians. Population frequency of HLA-B*1502, PPV, duration of treatment relative to life expectancy, and costs of alternative drugs are the key drivers influencing cost-effectiveness.
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ABSTRACT: Background Carbamazepine (CBZ), which is widely used in management of epilepsy or neuropathic pain, causes fatal severe cutaneous adverse reactions (SCARs). CBZ-induced SCARs are known to occur in strong association with human leukocyte antigen (HLA)-A*31:01 in Japanese and European populations. HLA genotyping is currently used to detect human HLA-A*31:01. Objective To establish a simple and rapid screening assay specific for HLA-A*31:01, the loop-mediated isothermal amplification (LAMP) method was employed on a sample Japanese population. Methods A set of LAMP primers targeting exon 2 of HLA-A*31:01 were designed. Thirty-two clinical samples including the representative HLA-A allele in Japan were used to assess the specificity of LAMP primers in the detection of HLA-A*31:01. Results The HLA-A*31:01-specific LAMP assay showed consistency with polymerase chain reaction reverse sequence-specific oligonucleotide probe (PCR-rSSO) and polymerase chain reaction-sequence based typing (PCR-SBT) results. Conclusions: High sensitivity and specificity of the HLA-A*31:01 LAMP assay was confirmed. Considering its convenience, the assay can be widely used to screen patients at high genetic risk of CBZ-induced SCARs.Journal of dermatological science 01/2013; DOI:10.1016/j.jdermsci.2013.11.013
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ABSTRACT: 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. 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. 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. 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.Epilepsia 07/2013; DOI:10.1111/epi.12325
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ABSTRACT: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions (SCAR) to drugs which are associated with significant morbidity and mortality. High risk drugs in Asia are similar to those reported worldwide. Human leukocyte antigen (HLA)-related risk alleles for carbamazepine and allopurinol SCAR are unique to Asians. Although prognostic scoring systems like the SCORTEN have been used for more than a decade, pitfalls and caveats need to be recognized, in particular in patients with multiple medical co-morbidities and systemic features in SJS/TEN. In centres without a tertiary Burns Centre, SJS/TEN patients can still be managed successfully in general and dermatology wards with well-executed supportive/nursing care. Controversy remains regarding the effectiveness of immunomodulation in reducing SJS/TEN morbidity, mortality and hastening re-epithelialization. Despite paucity of robust evidence, intravenous immunoglobulins and ciclosporin remain the most commonly used modalities worldwide. Acute and long-term ocular effects are an important source of morbidity for which emerging ophthalmic therapies appear promising. Quality of life issues have now become an important outcome in patients with SJS/TEN as they often impact survivors' future attitudes towards pharmacotherapy. Even though pharmacogenetic testing for high-risk drugs appears to be the panacea for preventing carbamazepine- and allopurinol-induced SJS/TEN in ethnic Asians, many issues remain before health regulators in our region can conclusively determine whether testing should be made mandatory or highly recommended as standard of care.10/2013; 3(4):215-223. DOI:10.5415/apallergy.2013.3.4.215