Objectives We evaluated the cost and efficiency of routine HLA-B*15:02 screening to prevent carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (CBZ-SJS/TEN) in Hong Kong. Methods Data were extracted from patients who commenced CBZ as the first-ever AED treatment or tested for HLA-B*15:02 allele in three years before policy implementation (pre-policy: 16 September 2005 to 15 September 2008) and three years after (post-policy: 16 September 2008 to 15 September 2011). Using published unit costs, we estimated the cost of screening by comparing the costs to prevent and treat CBZ-SJS/TEN. We compared the number of person-tests needed and the cost to prevent resultant death with cancer screening programs. Results The number of screening tests needed to prevent one case of CBZ-SJS/TEN was 442, and to prevent one resultant death was 1,474 to 8,840. The screening cost was $332 per person, of which 42% was attributed to an additional consultation to review result and prescribe appropriate medication. HLA-B*15:02 screening expended $146,749 to prevent a case of CBZ-SJS/TEN, and $489,386– $2,934,986 to prevent a resultant death. The corresponding numbers of tests and costs for mammography and Pap smear to prevent death due to breast and cervical cancers were 7,150 and 7,000, and $614,900 and $273,000, respectively. Comparing to the SJS/TEN treatment cost, HLA-B*15:02 screening would become cost saving if a point-of-care test of less than $37 was available. Conclusions HLA-B*15:02 screening is as efficient as mammography and Pap smear in preventing death. Development of point-of-care testing will vastly improve efficiency.
References
[1]
Glauser T, Ben-Menachem E, Bourgeois B, Cnaan A, Guerreiro C, et al. (2013) Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 54: 551–563.
[2]
Tennis P, Stern RS (1997) Risk of serious cutaneous disorders after initiation of use of phenytoin, carbamazepine, or sodium valproate: a record linkage study. Neurology 49: 542–546.
[3]
Franciotta D, Kwan P, Perucca E (2009) Genetic basis for idiosyncratic reactions to antiepileptic drugs. Curr Opin Neurol 22: 144–149.
[4]
Roujeau JC, Kelly JP, Naldi L, Rzany B, Stern RS, et al. (1995) Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med 333: 1600–1607.
[5]
Tangamornsuksan W, Chaiyakunapruk N, Somkrua R, Lohitnavy M, Tassaneeyakul W (2013) Relationship Between the HLA-B*15:02 Allele and Carbamazepine-Induced Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Systematic Review and Meta-analysis. JAMA Dermatol.
[6]
Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, et al. (2004) Medical genetics: a marker for Stevens-Johnson syndrome. Nature 428: 486.
[7]
Hung SI, Chung WH, Jee SH, Chen WC, Chang YT, et al. (2006) Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenet Genomics 16: 297–306.
[8]
Man CB, Kwan P, Baum L, Yu E, Lau KM, et al. (2007) Association between HLA-B*15:02 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Epilepsia 48: 1015–1018.
[9]
Chang CC, Too CL, Murad S, Hussein SH (2011) Association of HLA-B*15:02 allele with carbamazepine-induced toxic epidermal necrolysis and Stevens-Johnson syndrome in the multi-ethnic Malaysian population. Int J Dermatol 50: 221–224.
[10]
Chen P, Lin JJ, Lu CS, Ong CT, Hsieh PF, et al. (2011) Carbamazepine-induced toxic effects and HLA-B*15:02 screening in Taiwan. N Engl J Med 364: 1126–1133.
[11]
US Food and Drug Administration (2007) Information for Healthcare Professionals: Dangerous or Even Fatal Skin Reactions - Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, and generics). US Food and Drug Administration. Available: http://www.fda.gov/Drugs/DrugSafety/Post？marketdrugsafetyinformationforPatientsan？dProviders/ucm124718.htm. Accessed 18 November 2013.
[12]
UK Medicines and Healthcare products Regulatory Agency (2008) Carbamazepine: genetic testing recommended in some Asian populations. Available: http://www.mhra.gov.uk/Safetyinformation？/DrugSafetyUpdate/CON084888. Accessed 18 November 2013.
[13]
Leckband SG, Kelsoe JR, Dunnenberger HM, George AL, Jr., Tran E, et al.. (2013) Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B Genotype and Carbamazepine Dosing. Clin Pharmacol Ther.
[14]
Cheung NT, Fung V, Kong JH (2004) The Hong Kong Hospital Authority’s information architecture. Stud Health Technol Inform 107: 1183–1186.
[15]
Hong Kong Hospital Authority Clusters, Hospitals & Institutions. Available: http://www.ha.org.hk/visitor/ha_visitor_？index.asp?Content_ID=10036&Lang=ENG&Dime？nsion=100&Parent_ID=10004. Accessed 18 November 2013.
[16]
Census and Statistics Department HKSAR (2012) 2011 Population Census. Thematic Report: Ethnic Minorities. Census and Statistics Department, Hong Kong Special Administrative Region Government. Available: http://www.census2011.gov.hk/pdf/EM.pdf. Accessed 18 November 2013.
[17]
Ng M, Ng H Re: Genetic testing prior to prescription of carbamazepine. Available: http://www.cuhk.edu.hk/med/paf/ups/HLA-B？-15:02.pdf. Accessed 18 November 2013.
[18]
Cheung NT, Fung V, Chow YY, Tung Y (2001) Structured data entry of clinical information for documentation and data collection. Stud Health Technol Inform 84: 609–613.
[19]
Hong Kong Hospital Authority Fees and Charges. Available: http://www.ha.org.hk/visitor/ha_visitor_？index.asp?Content_ID=10045&Lang=ENG&Dime？nsion=100&Parent_ID=10044. Accessed 18 November 2013.
[20]
Hong Kong Monetary Authority Linked Exchange Rate System. Available: http://www.hkma.gov.hk/eng/key-functions？/monetary-stability/linked-exchange-rate？-system.shtml. Accessed 18 November 2013.
[21]
Cheung YK, Cheng SH, Chan EJ, Lo SV, Ng MH, et al. (2013) HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese. Epilepsia 54: 1307–1314.
[22]
Locharernkul C, Shotelersuk V, Hirankarn N (2011) Pharmacogenetic screening of carbamazepine-induced severe cutaneous allergic reactions. J Clin Neurosci 18: 1289–1294.
[23]
Dowling EC, Klabunde C, Patnick J, Ballard-Barbash R, International Cancer Screening N (2010) Breast and cervical cancer screening programme implementation in 16 countries. J Med Screen 17: 139–146.
[24]
Roujeau JC, Stern RS (1994) Severe adverse cutaneous reactions to drugs. N Engl J Med 331: 1272–1285.
[25]
Warner E (2011) Clinical practice. Breast-cancer screening. N Engl J Med 365: 1025–1032.
[26]
Raffle AE, Alden B, Quinn M, Babb PJ, Brett MT (2003) Outcomes of screening to prevent cancer: analysis of cumulative incidence of cervical abnormality and modelling of cases and deaths prevented. BMJ 326: 901.
[27]
Dong D, Sung C, Finkelstein EA (2012) Cost-effectiveness of HLA-B*15:02 genotyping in adult patients with newly diagnosed epilepsy in Singapore. Neurology 79: 1259–1267.
[28]
Rattanavipapong W, Koopitakkajorn T, Praditsitthikorn N, Mahasirimongkol S, Teerawattananon Y (2013) Economic evaluation of HLA-B*15:02 screening for carbamazepine-induced severe adverse drug reactions in Thailand. Epilepsia.
[29]
Tiamkao S, Jitpimolmard J, Sawanyawisuth K, Jitpimolmard S (2013) Cost minimization of HLA-B*15:02 screening before prescribing carbamazepine in Thailand. Int J Clin Pharm 35: 608–612.
[30]
Plevritis SK, Kurian AW, Sigal BM, Daniel BL, Ikeda DM, et al. (2006) Cost-effectiveness of screening BRCA1/2 mutation carriers with breast magnetic resonance imaging. JAMA 295: 2374–2384.
[31]
Karnon J, Peters J, Platt J, Chilcott J, McGoogan E, et al.. (2004) Liquid-based cytology in cervical screening: an updated rapid and systematic review and economic analysis. Health Technol Assess 8: iii, 1–78.
[32]
Roberts JD, Wells GA, Le May MR, Labinaz M, Glover C, et al. (2012) Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial. Lancet 379: 1705–1711.
[33]
Harr T, French LE (2010) Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet J Rare Dis 5: 39.
[34]
Hansen RC (1984) Blindness, anonychia, and oral mucosal scarring as sequelae of the Stevens-Johnson syndrome. Pediatr Dermatol 1: 298–300.
[35]
Wallack T, Lazar K (Februray 13, 2013) Family awarded $63 million in Motrin case. The Boston Globe. Boston, MA.
