BURDEN OF HEPATITIS C IN BULGARIA Prof. Guenka Petrova

Current patients` characteristics - 2013 -2015 (according to national epidemiology data)

Indicator % Total population Prevalence of HCV 1,5% People diagnosed with HCV infection (unofficial data) Proportion of patients, diagnosed with chronic HCV infection, receiving treatment (unofficial data) 1% Proportion of patients with chronic HCV infection on antiviral treatment Patients with HCV 1a on antiviral treatment Patients with HCV 1b on antiviral treatment Patients with HCV 1a on antiviral treatment with cirrhosis Patients with HCV 1b on antiviral treatment with cirrhosis

37% 10% 90%

Value 7265000 108975 54488 545 200 20 180 10 90

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Schematic view of the HCV development in Bulgaria

Approximate morbidity – 1.5% (108 975 души) 75-85%

15-25%

Spontaneous virus load

Chronic HCV

15-30%

Up to 18 mill BGN (9 mill €)

10-20 year

Stable disease

Slow progression

Cirrhosis (15,000 – 30,000 person)

Increasi ng cost to society

2-4%

End stage: НСС, transplantation, death 3

Our studies  Petrova G., J. Genov, M. Dimitrova, K. Pavlov. What is the cost of the bad control of chronic viral hepatitis. Sofia, ISPOR Bulgaria conference, March 2015  Dimitrova M., Petrova G., Genov J., Pavlov K., Mitov K., Savova A. COST ANALYSIS OF THE CHRONIC HCV-RELATED CIRRHOSIS IN BULGARIA. Value in health, 2015 Nov; 18 (3): A583  Dimitrova M, Petrova G, Kamusheva M, Savova A, Doneva M. Social Burden of Chronic HCV infection in patients with hepatocellular carcinoma. Value Health. 2015 Nov; 18(7): A476  Petrova G., M. Dimitrova. Cost-effectiveness assessment of liver disease therapy. EASL conference, Budapest, 23-25 JUNE, 2016

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1st study – Costs for real life therapy of patients

with chronic HCV infection and cirrhousis

Healthcare resources used for cirrhotic patients Medicinal products

% utilization No of patients

Ceftriaxone Ciprofloxacin Terlipressin Esomeprasole Albumin

41% 38% 4% 41% 44%

122 113 12 124 132

Spironolactone+ Furosemide

38%

115

Propranolol/Carvedilol (avg) Bands for endoscopic treatment Norfloxacin L-ornithine-L-aspartat Endosopic treatment Lactulose + L-ornithine-L-aspartat Abdominal paracentesis

48% 15% 10% 15% 15% 14% 38%

145 45 30 45 45 42 115

Albumin up to 2 vails per patient Hospitalizations

44% 100%

132 301

Dose/Therapeutic course

Payer

2 х 1 g i.v. / 7-10 days 2 x 500 mg i.v. / 7-14 days 7-10 days; 4x2 mg i.v. 2x1 fl. i.v. 1-10 days; 20-60g/ daily Spironolactone 200 mg/ daily; Furosemide 40-160 mg/ daily for 6 months Carvedilol 2x12,5-25 mg; Propanolol 3x40 mg/ daily for 1 year 6-20 bands per package 400 mg/daily for 1 year 5 - 10 mg/ 6 months

Hospital Hospital Hospital Hospital Patients

5 - 10 mg 1-10 days; 20-60g/daily

Patients Patients Patients Patients Patients NHIF NHIF NHIF NHIF NHIF 5

Total costs of treatment of cirrhosis/BGN/

1000000 800000

804 850

600000 357 525

400000 200000

50 958

0 Direct medical costs of NHIF

Direct medical costs of hospital

Direct medical costs of patients

Total costs for 301 patients with cirrhosis for 3 years = 1 213 333 BGN (620 367 euro); Average cost per patient per 1 year- 1,343 BGN ( 687 euro)

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2nd study  Prospective, real-life, observational study on demographic (age and sex), clinical (Child-Pugh stage, ascites, portal hypertension, esophageal varices, encephalopathy, etc) and data on utilized healthcare resources (cirrhosis drug therapy, therapy of cirrhosis-related complications, hospitalizations) were collected. – Retrospective budget model, evaluated the total direct medical costs and indirect costs. • Patients groups and subgroups 301 patients with chronic HCV infection and cirrhosis, monitored in the University hospital “Queen Joanna-ISUL” for 3-year period (2012-2014). Patients were further divided into subgroups depending on the severity of the disease according to Child-Pugh. • Healthcare resources Healthcare resources were divided into three subgroups – utilized by the National Health Insurance Fund (NHIF), the hospital and the patients. The subdivision was necessary because NHIF does not cover all healthcare services and there were expenditures made by the hospital and the patients, namely for the medicinal products and the medical supplies. • Costs Micro-costing approach based on the data for the utilized healthcare resources on hospitalizations, highly specialized interventions, drugs and medical supplies. 7

Demographic and clinical data

Total number of patients Males (76%) Females (24%) Follow-up duration (avg) Severity of disease (Child-Pugh) on baseline - A (57,1%)

Severity of disease (Child-Pugh) on baseline - B (37%) Severity of disease (Child-Pugh) on baseline - C (6,64%)

1-120 months months on avg)

301 228 73 (12

172

109 20 8

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Complications and concomitant pathology Rate and type of complication, diagnosed at baseline Ascites (38,2%) Spontaneous bacterial peritonitis (10%) Other infection (urological, pneumonia, soft tissue infections) - 30% Encephalopathy (18,6%) Esophageal varices 3-4 grade (incl. haemorrhage) (41,2%) Esophageal varices 1-2 grade (58,8%) Concomitant pathology Heart diseases (35,5%)

No patients 115 30 90 56 124 177

107 9

Resources used Total number of hospitalizations Number of hospitalizations due to decompensated liver disease/cirrhosis (Health service, covered by the NHIF) Number of hospitalizations due to highly specialized interventions in gastro-intestinal disorders (Health service, covered by the NHIF) Number of hospitalizations due to highly specialized interventions of the hepatobiliary system, pancreas and peritoneum (Health service, covered by the NHIF) Average number of hospitalizations per patient Average hospital stay (days) on first hospitalization per patient Average time (months) of follow-up per patient

847 386

281

180 3 17 12 10

5

30

120

27

100

25 N patients with cirrhosis and hepatitis

20

Concomitant diseases

97

80

N patients with cirrhosis and hepatitis

60

15

12

11

40

10

15

20

5 1

1

0

2 0

0

4

1

0

3

0

• Out of 123 patients with cirrhosis: • 97 have only cirrhosis • 23 have hepatitis and cirrhosis • 15 are with HBV and cirrhosis • 4 are with HCV and cirrhosis • 1 are with hepatitis А+С and cirrhosis • 3 сare unidentified • 20 са били с ЧН • 5 are with liver insufficiency and hepatitis • 15 are with liver insufficiency and cirrhosis

• Out of 54 cirrhotic patients: • 27 have only cirrhosis • 27 have hepatitis and cirrhosis • 12 with HBV and cirrhosis • 11 with HCV and cirrhosis • 1 with hepatitis В+С and cirrhosis • 1 with hepatitis А • 2 undefined

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3rd Study - DALY Life expectancy for male is 70 years and for female - 79 1

DALY 1756,03

YLL

L

N 1243;864;417

798,17

YLD 957,86 1. www.nsi.bg; 2. Ly et al 2012; 2. Perz 2006; 3. CDC 2013b; 4. Chen & Morgan 2006

years N Dead L – health status loss L – cirrhosis L - cirrhosis L – HCC DW cirrhosis DW HCC DW hepatitis L- years of life lost L – surveillance

0,3472; 0,301; 0,2555 над 59

60-69

над 70

113 98 0,3472

164 144 0,301

0,194 0,508 0,75 1243 3

0,194 0,508 0,75 864 3

169 139 0,2555 27 общо 97 общо 445 общо 0,194 0,508 0,75 417 3

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3rd study – Social burden of HCV in Bulgaria

• Years of life lost at the end of 2014 798,17 • Years of life in disability - 957,86 • DALY = 1 756,03

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4th study - Patients with HCV genotype 1a without cirrhosis

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ICER and SA -HCV genotype 1a, no cirrhosis Strategy

Cost

double and triple therapy new DAAs

Incr Cost

37063,6 103317,5

66253,9

Eff

Incr Eff

0,53 0,98

Incr C/E

0,44

149220,5

15

Patients without cirrhosis genotype 1b

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ICER and SA - HCV genotype 1b, no cirrhosis Strategy

Cost

double and triple therapy new DAAs

Incr Cost

37063,6 103317,5

Eff

66253,9

Incr Eff

0,53 0,99

Incr C/E

0,46

144344

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o Discussion  ICER – The ICER of both new INF-free therapies is above the 3xGDP threshold for Bulgaria; – The ICER for both new INF-free therapies is lower for patients without cirrhosis for both subgenotypes compared to patients with cirrhosis; – The ICER for both new INF-free therapies is more favourable for patients with HCV genotype 1b compared to patients with genotype 1a.

 Limitations of the cost-effectiveness model – Only direct medical costs for drug therapy were considered; – Direct medical costs related to treatment of ADRs (anemia, skin reactions, depression) of the dual and triple therapy were not considered due to insufficient data for the therapeutic regimes and duration of treatment for the patients.

 Future possibilities – Adding the cost of ADRs to the cost of therapeutic regime with dual or triple therapy will decrease the value of the ICER for the new INF-free therapies.

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o Current practice in Bulgaria  Positive Drug List (PDL) – Both new INF-free regimes are included in the PDL with 100% reimbursement and will be paid by the National Health Insurance Fund (NHIF) from this year – Due to changes in the legislation MAH are obliged to provide discounts to NHIF to keep reimbursement status – The latter is expected to lead to further decrease in the values of the ICER for the new DAAs – Telaprevir is excluded from PDL from this year

 National Health Insurance Fund – As of 01.03.2016 the NHIF has published new criteria for treatment of adult patients with chronic HCV infection in compliance with EASL Guidelines and National Pharmacotherapeutic Guideline: - New INF-free therapeutic regimes are considered as I-st line therapy for patients with genotype 1 if available in Bulgaria - Treatment with new DAAs could be initiated only in patients with chronic HCV infection with METAVIR 03 and METAVIR 04 stage. Treatment of patients with METAVIR 02 could be only started after careful consideration of the specialist 19 - Double and triple therapy are treatment of choice only if patients are contraindicated for treatment with the new DAAs

Conclusion  Market access to innovative medicinal products – Market/patient access to innovative medicinal products has improved since 2013 – The NHIF has reconsidered its criteria for treatment adults with chronic hepatitis C infection in compliance with the international guidelines – Currently priority to treatment is given only to patients at advanced stages of the disease – NHIF will reimburse 100% the treatment with new DAAs for the next three years (2016-2018) – Financial risk-sharing agreements with MAHs are in force to reduce the financial burden on the NHIF budget – In 2018 reconsideration on reimbursement status will be done

 Cost- Effectiveness of new DAAs in the Bulgarian healthcare setting – Further observational studies are needed to assess the effectiveness of the new DAAs in real-world 20 and their cost-effectiveness

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Thank you for your attention

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