Cost Effectiveness of HCV treatment in Asia
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1 Cost Effectiveness of HCV treatment in Asia A/P Dan Yock Young Chair, University Medicine Cluster. NUHS Head, Dept of Medicine. YLL SoM NUS Senior Consultant. Div of Gastro/Hepatology. National University Health System Adjunct,. Cancer Science Institute, NUS Associate Faculty, Genome Institute of Singapore.. Clinical Care Education Research
2 COI Disclosure Information Advisory Board BMS, Gilead, Novartis, AbbVie, MSD Education and Research Funding BMS, Gilead Novartis, AbbVie, Sanofi Aventis
3 Disease burden of Hepatitis C Lemoine et al. Future Virology 2013
4 Natural History and Cost of HCV Annual Uninfected Chronic Hep Cirrhosis End-stage HCC Rx/transplant Cost (SGD) $10K $17K $22K $60K $ K Lauer GM, Walker BD. N Engl J Med 2011 McAdam-Marx, J Manag Care Pharm 2011 Gordon, Hepatology 2012
5 Advances in HCV treatment Sustained Virologic Response % Year Side Effect Cost SGD (per course) IFN 6mo IFN 12mo IFN/RBV PEG/RBV PEG/RBV/PI Peg/RBV/G2 PEG/RBV/2 nd All All oral oral AV Gen AV DAA DAA G2 All New-gen oral AV all oral G3 DAA $6K $12K $16K $24K $36K $88K $40-100K $85K IFN, Interferon; RBV, ribavirin, PEG, pegylated interferon; PI, protease Inhibitor; DAA, Direct antiviral Side Effects (esp if cirrhotic) Minimal Moderate Serious Severe Adapted from Rehermann Nature Reviews Gastroenterology & Hepatology 2016
6 EASL guidelines 2015 AASLD/IDSA guidelines Regimen HCV Genotype 1a 1b 4 5 or 6 SOF + PR 12 wks 12 wks 12 wks SMV + PR 12 wks (naive or relapse) 24 wks (partial/null) 12 wks (naive or relapse) 24 wks (partial/null) Not recommended LDV/SOF 8-12 wks, no RBV 12 wks, no RBV 12 wks, no RBV OBV/PTV/RT V + DSV 12 wks + RBV 12 wks, no RBV Not recommended Not recommended OBV/PTV/RT V Not recommended 12 wks + RBV Not recommended SOF + SMV 12 wks, no RBV 12 wks, no RBV Not recommended SOF + DCV 12 wks, no RBV 12 wks, no RBV 12 wks, no RBV
7 Factors affecting Standard of Care Efficacy Cost-effectiveness Affordability Patient- Reported Outcomes Accessibility
8 No. of PUBMED publications HCV AND cost-effectiveness HCV Guidance does not utilize cost-effectiveness analysis to guide recommendations at this time. 0
9 Cost effectiveness of all-oral DAA Reference Drug Regimen Base Case Comparison ICER (USD/QALY) Rein CID 2015 Najafzadeh Ann Int Med 2015 Chhatwal Ann Int Med 2015 LDV/SOF 3D No Rx $ $35000 LDV/SOF No RX GT1 $ SOF based therapy SOC $ Johnson EASL D No Rx Zhang BMC Gastroenterology Chahal et al JAMA D LDV/SOF SOC: Peg IFN/RBV/ TVR GT1 no cirrhosis: 3D most cost saving GT1 cirrhosis: Harvoni LDV/SOF All:F3/4:F2:F1:F0 $39 475: $ : $81 165: $ Leidner Hepatology 2015 LDV/SOF F2 vs F3 $ LDV, ledipasvir; SOF,sofosbuvir; 3D, Viekiera pak; SOF; GT, genotype
10 Cost-effectiveness vs affordability Treating half of the eligible patients in US would cost $134 billion and is 1/8 th of US health budget Treating all eligible patients in the US compared to SOC would cost an additional USD 65 billion and offset USD 16 billion of costs. Chhatwal et al 2015 The Guardian 16 Jan 2015
11 SUPER SPENDING U.S. TRENDS in HIGH-COST MEDICATION USE AN EXPRESS SCRIPTS REPORT MAY 2015
12 EPIDEMIOLOGY OF HCV IN ASIA-PACIFIC Rank Continent 2010 GDP per capita (US$) World Average 18,351 1 Oceania 39,052 2 North America 32,077 3 Europe 25,434 4 South America 9,024 5 Asia 2,941 6 Africa 1,576 7 Antarctica 0 World Health Organization. Hepatitis C - Global Surveillance Update. Weekly Epidemiological Record 75:17-28, World Bank 2012
13 Cost-effective regimen will save lives? Top 10 causes of death by income WHO 2012
14 Drug Access - Affordability Treatment of Hepatitis C has shifted from a medical limitation to a socio-economic access challenge. Who is paying for the drug? xxx Self-paying Single health payer with universal health coverage
15 Patient Affordability Have and Have nots: Hong Kong: Oral DAA second line Rx Singapore. Taiwan : National assistance programme for selected patients Generics
16 Social barrier: Access to Care in Asian Health Systems Clean blood supply Disposable needles Infrastructure for universal health Health education Basic education Perfectotest point of care, Antigen test kit, RNA, Genotype Perfectovir pangenotypic, zero resistance
17 CEA for HCV in Asia 1. Natural history of HCV may be different in Asia a. More patients may be aviraemic b. Rate of progression of fibrosis may be slower c. Is the risks of HCV complications lower? 2. Tolerability of interferon/ ribavirin Asians can tolerate side effects better
18 Percentage of SVR by genotypes of rs DL Ge et al. Nature 461, (2009) doi: /nature08309
19 CEA analysis in Asia No Treatment PegIFN/ RBV PegIFN/RBV/ BOC PegIFN/ RBV/SOF IL-28 PR/BOC IL-28 PR/SOF SOF/ RBV SOF/SMV SOF/LDV OBV/PTV/DSV Zhao et al. JGH 2016
20 Lifetime cost, health benefits of treatment strategies (compared to no treatment) Treatment strategies Cost (USD) QALY ICER (USD /QALY gained) Remarks Lifetime risk per 10,000 patients DC HCC LT Liv-Death No treatment 31, ,668 2, ,656 BOC/PR 20, ,202 undominated IL-28B guided BOC/PR 22, ,767 abs. dominated PR 24, , IL-28B guided SOF/PR 33, ext. dominated OBV/PTV/r-DSV+/-RBV 55, ,277 undominated SOF/PR 65, ,901 abs. dominated SOF/LDV 76, , SOF/RBV 133, , SOF/SMV 153, , Hepatitis C Treatment is cost saving compared to no treatment Zhao et al. JGH 2016
21 Lifetime cost, health benefits of treatment strategies (compared to common baseline or next best treatment) Treatment strategies Cost (USD) QALY ICER (USD/QALY gained) compared to common baseline ICER (USD/QALY gained) compared to next best treatment Remarks BOC/PR 20, IL-28B guided BOC/PR 22, ,674-9,674 dominated PR 24, ,851-8,851 No treatment 31, ,202-4,202 IL-28B guided SOF/PR 33, , ,950 Extendedly dominated OBV/PTV/r-DSV+/-RBV 55, ,828 33,070 SOF/PR 65, , ,250 Dominated SOF/LDV 76, ,641 Nil SOF/RBV 133, ,257, ,173 SOF/SMV 153, ,262-1,399,529 PR/Boc RGT and all oral antiviral are cost-effective Zhao et al. JGH 2016
22 Oral DAA in Non-cirrhotic HCV The all-oral therapies such as Ombitasvir/paritaprevir/ritonavirdasabuvir and sofosbuvir/ledipasvir had ICER of USD38,780 to USD62,645 relative to BOC/RGT and would be considered to be within cost-effective range given willingness to pay threshold at USD 52,500 (one GDP per capita in Singapore in 2015). Zhao et al. JGH 2016
23 Cirrhotic HCV If cirrhotic. Rx experienced, oral DAA are more cost-effective the ICER of Viekira Pak and SOF+LDV relative to BOC/RGT was USD 4,505 and USD 10,649 respectively. Zhao et al. JGH 2016
24 Accessibility based on Cost-effectiveness? Dear Minister of Health, Treating HCV with all oral antiviral is cost-effective. Can you give us 2.28 billion USD to save 5100 related deaths? Private 2nd line Stratified Rx
25 Model incorporating retreatment Zhao et al. JGH 2016
26 Non-cirrhotic HCV But if retreatment is taken into account, using the oral DAA as first line therapy becomes less cost-effective as opposed to reserving DAA as second line therapy, Oral regimens are only cost-effective (<USD50000/Qaly) compared to Standard of care (Peg-IFN/Boceprevir/Response guided therapy) if they are less than SGD47,997 for each treatment course Zhao et al. JGH 2016
27 Optimising CEA: Roadmap Strategy Roadmap strategy ICER, USD 14,336 Reduce total budget by 65% with 98% of outcome survival. Zhao et al. JGH 2016 Lim et al Korean J Intern Med 2015
28 Rationalised treatment strategy Identify patients who truly need oral DAA Cirrhosis Interferon experienced failures Interferon intolerant Predictive poor responders to IFN based strategy Patients who need it most will be able to get access rather than those who can afford it Zhao et al. JGH 2016
29 Understanding the drivers to tweak costeffectiveness for the administrators Liver Transplant Cost of drugs SVR Health Infrastructure
30 Should I buy a Lamborghini or take the MRT? Lamborghini MRT If money is not a problem, buy the Lamborghini. The MRT is the most cost-efficient transport
31 Treatment of Hepatitis C has shifted from a medical limitation to a socio-economic access challenge. If we can find out who really needs to get on the train.
32 Acknowledgements Ms Monica Teng, Dr Zhao Ying Jiao, Mr Lim Boon Peng, Dr Khoo Ai Leng and Ms Lin Liang, Dr Calvin Koh
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