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.
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.
Authors: Teri A Manolio; Marc Abramowicz; Fahd Al-Mulla; Warwick Anderson; Rudi Balling; Adam C Berger; Steven Bleyl; Aravinda Chakravarti; Wasun Chantratita; Rex L Chisholm; Vajira H W Dissanayake; Michael Dunn; Victor J Dzau; Bok-Ghee Han; Tim Hubbard; Anne Kolbe; Bruce Korf; Michiaki Kubo; Paul Lasko; Erkki Leego; Surakameth Mahasirimongkol; Partha P Majumdar; Gert Matthijs; Howard L McLeod; Andres Metspalu; Pierre Meulien; Satoru Miyano; Yaakov Naparstek; P Pearl O'Rourke; George P Patrinos; Heidi L Rehm; Mary V Relling; Gad Rennert; Laura Lyman Rodriguez; Dan M Roden; Alan R Shuldiner; Sukdeb Sinha; Patrick Tan; Mats Ulfendahl; Robyn Ward; Marc S Williams; John E L Wong; Eric D Green; Geoffrey S Ginsburg Journal: Sci Transl Med Date: 2015-06-03 Impact factor: 17.956
Authors: H Y Chong; Z Mohamed; L L Tan; D B C Wu; F H Shabaruddin; M Dahlui; Y D Apalasamy; S R Snyder; M S Williams; J Hao; L H Cavallari; N Chaiyakunapruk Journal: Br J Dermatol Date: 2017-09-21 Impact factor: 9.302
Authors: Susan R Snyder; Jing Hao; Larisa H Cavallari; Zhi Geng; Amanda Elsey; Julie A Johnson; Zahurin Mohamed; Nathorn Chaiyakunapruk; Huey Yi Chong; Maznah Dahlui; Fatiha H Shabaruddin; George P Patrinos; Christina Mitropoulou; Marc S Williams Journal: Public Health Genomics Date: 2019-06-12 Impact factor: 2.000
Authors: K E Caudle; A E Rettie; M Whirl-Carrillo; L H Smith; S Mintzer; M T M Lee; T E Klein; J T Callaghan Journal: Clin Pharmacol Ther Date: 2014-08-06 Impact factor: 6.875