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September 18, 2012; 79 (12) Articles

Cost-effectiveness of HLA-B*1502 genotyping in adult patients with newly diagnosed epilepsy in Singapore

Di Dong, Cynthia Sung, Eric Andrew Finkelstein
First published September 5, 2012, DOI: https://doi.org/10.1212/WNL.0b013e31826aac73
Di Dong
From the Health Services & Systems Research Program (D.D., E.A.F.) and Emerging Infectious Diseases Program (C.S.), Duke-NUS Graduate Medical School, Singapore; Health Sciences Authority (C.S.), Singapore; and Global Health Institute (E.A.F.), Duke University, Durham, NC.
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Cynthia Sung
From the Health Services & Systems Research Program (D.D., E.A.F.) and Emerging Infectious Diseases Program (C.S.), Duke-NUS Graduate Medical School, Singapore; Health Sciences Authority (C.S.), Singapore; and Global Health Institute (E.A.F.), Duke University, Durham, NC.
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Eric Andrew Finkelstein
From the Health Services & Systems Research Program (D.D., E.A.F.) and Emerging Infectious Diseases Program (C.S.), Duke-NUS Graduate Medical School, Singapore; Health Sciences Authority (C.S.), Singapore; and Global Health Institute (E.A.F.), Duke University, Durham, NC.
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Citation
Cost-effectiveness of HLA-B*1502 genotyping in adult patients with newly diagnosed epilepsy in Singapore
Di Dong, Cynthia Sung, Eric Andrew Finkelstein
Neurology Sep 2012, 79 (12) 1259-1267; DOI: 10.1212/WNL.0b013e31826aac73

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Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

GLOSSARY

CBZ=
carbamazepine;
ICER=
incremental cost-effectiveness ratio;
NPV=
negative predictive value;
PHT=
phenytoin;
PPV=
positive predictive value;
QALY=
quality-adjusted life year;
QoL=
quality of life;
SF=
seizure-free;
SJS=
Stevens-Johnson syndrome;
TEN=
toxic epidermal necrolysis;
VPA=
valproate

Footnotes

  • Study funding: Supported by a Duke-NUS Graduate Medical School internal grant.

  • Supplemental data at www.neurology.org

  • Received November 30, 2011.
  • Accepted May 1, 2012.
  • Copyright © 2012 by AAN Enterprises, Inc.
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Letters: Rapid online correspondence

  • Re:HLA-B*1502 genotyping for preventing phenytoin-induced Stevens-Johnson syndrome and toxic epidermal necrolysis ?
    • Di Dong, PhD candidate, Duke-NUS Graduate Medical School, Singaporedong_di87@nus.edu.sg
    • Cynthia Sung, Singapore; Eric Andrew Finkelstein, Singapore.
    Submitted November 13, 2012
  • HLA-B*1502 genotyping for preventing phenytoin-induced Stevens-Johnson syndrome and toxic epidermal necrolysis ?
    • Shuen-Iu Hung, Institute of Pharmacology, School of Medicine, Infection and Immunity Research Center, VYM Genome Resihung@ym.edu.tw
    • Wen-Hung Chung, Shuen-Iu Hung, Taipei, Taiwan
    Submitted November 07, 2012
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