Open Access

Cost-effectiveness analysis of oral anti-viral drugs used for treatment of chronic hepatitis B in Turkey

  • Guvenc Kockaya1,
  • Akin Kose1,
  • Fatma Betul Yenilmez2Email author,
  • Oktay Ozdemir3 and
  • Ece Kucuksayrac1
Cost Effectiveness and Resource Allocation201513:21

DOI: 10.1186/s12962-015-0046-8

Received: 13 March 2015

Accepted: 18 November 2015

Published: 10 December 2015

Abstract

Background

All international guidelines suggested that Tenofovir and Entecavir are the primary drugs at the first line therapy for the treatment of chronic hepatitis B (CHB). However, in Turkey these medications reimbursed at the second line therapy according to the Healthcare Implementation Notification. The aim of this study is to compare the cost effectiveness of oral antiviral treatment strategies in CHB for Turkey using lamuvidine, telbuvidine, entecavir, and tenofovir as medications.

Methods

The analysis was conducted using Markov models. The analysis scenarios based on first line treatment options with Lamuvidine, Telbuvidine, Entecavir, and Tenofovir as the medications. In the analysis, inadequate response or resistance after receiving 12 months of the treatment with Entecavir and Telbivudine were compared to the results found from switching from Entecavir to Tenofovir or from switching from Telbuvidine to Tenofovir. In additional, inadequate response or resistance after receiving 6 months of the treatment for Lamivudine was compared to the results found from switching from Lamivudine to Tenofovir. The study population included men and women, who were 40 years of age. The patients` compliance was estimated 100 % for all of the therapy options. The model duration was constructed to evaluate, treatment strategy duration of 40 years. The cost of medications, examinations/follow-ups and complications were included in the model. Years of Potential Life Lost was used as the health outcome. An incremental cost-effectiveness ratio analysis has been conducted.

Results and discussion

While the minimum years of life lost was found as 0.22 with tenofovir treatment in 5 years, treatment cost was calculated as 12,169 TL. These values were detected as 0.56 years and 7727 TL, 0.37 years and 12,770 TL, respectively for lamuvidine and telbuvidine treatments. The maximum years of life lost and treatment cost was with lamuvidine treatment were detected as 1.60 years and 18,813 TL and, secondly 0.89 years and 24,007 TL for lamuvidine-tenofovir treatment during 10 years. The minimum years of life lost and cost are 0.54 year and 35,821 TL for tenofovir treatment during 10 years. The minimum years of life lost and cost were determined as 1.21 years and 52,839 TL for tenofovir treatment strategy during 20 years. During 30 years period, tenofovir treatment was found to have the minimum years of life lost (1.73 years) and minimum cost (84,149 TL). When the results of 40 years period were analyzed, years of life lost and costs are 2.06 years and 119,604 TL, 2.13 years and 162,115 TL, 2.13 years and 161,642 TL, 6.52 years and 147,245 TL, 3.20 years and 132,157 TL, 4.10 years and 151,059 TL and 3.05 years and 138,182 TL for tenofovir, entecavir, entecavir-tenofovir, lamuvidine, lamuvidine-tenofovir, telbivudine and telbivudine-tenofovir.

Conclusions

In the model presented in this study, in cost effectiveness analysis about CHB treatments, Tenofovir was found to be one of the cost effective methods in comparison with other treatment strategies different time intervals. Beyond this achievement Tenofovir has shown to reduce cumulative treatment cost in first line CHB treatment when compared with regard to 40 year cumulative treatment cost.

Keywords

Chronic hepatitis B Cost effectiveness Oral antiviral treatment

Background

Hepatitis B is among the most common infectious diseases worldwide. At least 2 billion individuals are estimated to have been infected with the Hepatitis B virus (HBV), and 378 million individuals (6 % of the world’s population) are estimated to be chronic carriers worldwide. Cirrhosis, hepatic failure, or hepatocellular cancer are known to develop in approximately 40 % of all chronic hepatitis B (CHB) cases [1, 2].

The prevalence of the hepatitis B surface antigen (HBsAg) was determined as 4.57 % according to a meta-analysis conducted to investigate HBV epidemiology in Turkey. The confidence interval (CI) was determined as 3.58–5.76, and the estimated number of CHB cases was 3.3 million. This ratio increases to 9.8 % in the eastern part of Turkey. According to the epidemiologic data obtained between 1999 and 2009, while Hepatitis B prevalence is 3.23 % in the age group of 0–14 years, it is 5.77 % in the age group of 15–24 years. This ratio is 7.08 % in the 25–34 age group, 6.93 % in the 35–44 age group, 6.13 % in the 45–54 age group, and 5.02 % in the 55–64 age group. Hepatitis B surface antigen (HBsAg) prevalence increases with age according to this study [3].

Oral antiviral treatment is the most convenient way to control and stabilize the CHB disease. The indications are generally the same for HBeAg positive and negative patients [4]. Treatment is usually based on assessing the combination of three criteria: serum HBV DNA values, ALT values, and the stage of the hepatic disease [4].

The goal of treatment for Chronic Hepatitis B is to prevent the progression to cirrhosis, reducing the need for liver transplantation and improving the quality of life of the patient. Both national and international CHB treatment guidelines reveal that HBV DNA should be strongly suppressed for achieving these goals. With the treatment, the histopathological findings of the liver and the biochemical parameters are improved and the long-term complications of CBH are reduced as well [4].

Some current treatment guidelines, such as the European Association for the Study of the Liver (EASL), the American Association for the Study of Liver Diseases (AASLD) and the Asia Pacific Association for the Study of the Liver (APASL) recommend potent Oral Anti-viral (OAV) treatments as the first choice in initial therapy for achieving the specified goals [46]. In Turkey, changes have been made in Healthcare Reimbursement Rules to be aligned with International Hepatology Management and Treatment guidelines. Potent OAV treatments, such as Tenofovir and Entecavir, were approved to be used for a low viral loaded patient population in 2014 [8].

Tenofovir maintains the effective suppression of HBV DNA through 8 years of treatment with no evidence of TDF resistance in contrast to other agents [8]. In addition to the effective suppression of HBV DNA with a TDF treatment, there have been histological improvements in a 5-year treatment both in cirrhotic and non-cirrhotic CHB patients [9]. As Entecavir has a 1.2 % resistance potential in a naïve treatment group, Entecavir patients should also be closely monitored for resistance. In addition, in long-term use, the cumulative probability of Entecavir resistance development in lamivudine-refractory patients was reported to be as high as 57 % over 6 years of treatment [11]. In a 2-year Globe trial, it was shown that the Telbivudine resistance rates were 25.1 % for HBeAg positive patients and 10.8 % for HBeAg negative patients. The M204I signature mutation was the primary basis for Telbivudine resistance, with secondary mutations detected at the L80, L180, and other codons. In vitro studies have shown that HBV with the M204I mutation remains sensitive to the nucleotide analogues adefovir, dipivoxil, and tenofovir [7].

Lamivudine has been approved in Turkey since 2000. For a long period of time, lamivudine was the only treatment before Entecavir approval in 2006. Tenofovir and Telbivudine were approved in Turkey in 2007 and 2008, respectively. Based on the Globe [7] study’s results, a road map concept has been generated by the Social Security Institute [10]. From 2009 to 2015, Lamivudine and Telbivudine was stratified as the first line treatment options for low viral loaded patients (HBV DNA <104 IU/mL). As a result, 2/3 of HBV patients had been treated with Lamivudine and Telbivudine. Tenofovir was only prescribed for high viral loaded patients (HBV DNA >104 IU/mL) or patients with a detectable HBV DNA level after 6 months of therapy with Lamivudine or Telbivudine.

This analysis compares Lamivudine, Telbivudine, Entecavir, and Tenofovir, the oral antiviral agents used for first line CHB treatment according to the Health Application Notification, which defined the reimbursement process in Turkey.

Methods

Treatment strategies

The Markov model was used in the present analysis. The Markov model is designed to include the entire disease whether the patients respond to therapy or not, complications develop in the case of irresponsiveness to therapy, complications progress in years, and a follow up for the patients until death (Fig. 1). In the analysis scenarios, Lamivudine (3TC), Telbivudine (LdT), Entecavir (ETV), and Tenofovir (TDF) use was planned for first line therapy. Treatments that switched to Tenofovir from Entecavir (ETV- TDF) and to Tenofovir from Telbivudine (LdT-TDF) in the case of an inadequate response or resistance development after 12 months or that switched to Tenofovir from Lamivudine (3TC-TDF) in the case of an inadequate response or responsiveness 6 months later were included in the analysis. A single strategy was also included during the model time in all molecules in transitional treatments. The resistance rates of the drugs and the estimated 5-year virologic response rates for each treatment were obtained from published studies.
Fig. 1

Chronic hepatitis B treatment Markov model

Treatment population

The age for beginning treatment was 40 years, and the duration of treatment was 40 years, which is consistent with the life expectancy. Of the patients, 50 % were assumed to be male and 50 % were assumed to be female in the Turkish population [8]. They were assumed to be 100 % compliant to therapy. The HBeAg positivity rate was assumed to be 30 % [9]. The transition probability between disease stages was taken from the analysis of Kanwal et al. [13]. (Table 1). Tables 2 and 3 show the response rates of CHB treatments in the model and the resistance rates. The rates of resistance developing during the therapy and the cumulative resistance rates for the first 3 years of therapy were obtained from the data of the paper published by Marcellin et al., and the assumptions were used for the resistance rates after 3 years [11, 12]. The resistance data of Entecavir treatment for the first 6 years were obtained from the study published by Tenney et al., and the assumptions were made for the following years [14]. The Lamivudine resistance data were calculated proportionally with the yearly resistance rates of the patients who had a high viral load for the fourth and the fifth years, and it was assumed to be half of the previous year for each year after the fifth year [15]. The Telbuvidin response data were obtained from the data of Zeuzem et al. and calculated proportionally with 3TC treatment at the third year and thereafter [16] (Table. 2, 3).
Table 1

Transition rates between chronic hepatitis B and diseases [13]

 

Decompensated cirrhosis

Hepatocellular cancer

Transplantation

Death (%)

Compensated cirrhosis

7.3 %

3.4 %

0.0 %

4.9

Decompensated cirrhosis

3.4 %

20.0 %

19.0

Hepatocellular cancer

25.0 %

43.3

transplantation

6.9

Table 2

Response rates to chronic hepatitis B treatments [1720]

24th week

TDF

ETV

3TC

LAM

LdT

TDF

ETV

3TC

LAM

LdT

<300

84.8

84.8

73.0

71.0

80.0

48.9

37.0

34.0

32.0

45.0

300–104

9.7

9.7

15.0

20.0

15.0

32.5

40.0

26.0

31.0

31.0

104–105

2.7

2.7

3.6

2.7

1.5

8.9

11.0

12.0

11.1

7.2

105–106

0.2

0.2

1.5

1.1

0.6

0.8

1.0

5.0

4.6

3.0

>106

2.7

2.7

6.9

5.2

2.9

8.9

11.0

23.0

21.3

13.8

48th week

          

<300

93.2

93.3

75.6

71.4

88.3

76.1

69.1

39.8

40.4

60.0

300–104

4.2

4.1

12.5

18.4

8.0

19.1

24.7

18.2

28.1

21.5

104–105

1.6

1.6

5.1

7.5

3.3

3.4

4.4

11.7

18.1

13.8

105–106

0.3

0.3

2.0

0.8

0.1

0.5

0.6

9.3

4.1

1.4

>106

0.6

0.6

4.8

1.9

0.3

0.9

1.2

21.0

9.3

3.3

Values are expressed as %

Table 3

Resistance to therapy for chronic Hepatitis B treatment [1116]

Years

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

Resistance

 TDF

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

 ETV

0.2

0.3

0.7

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

 3TC

6.7

11.3

21.0

11.3

6.4

3.2

1.6

0.8

0.4

0.2

0.1

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

 LtD/Hbe−

1.1

2.2

4.1

2.2

1.2

0.6

0.3

0.2

0.1

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

 LtD/Hbe+

5.0

6.3

11.6

6.3

3.5

1.8

0.9

0.4

0.2

0.1

0.1

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

Cumulative resistance

 TDF

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

0.0

 ETV

0.2

0.5

1.2

1.2

1.2

1.2

1.2

1.2

1.2

1.2

1.2

1.2

1.2

1.2

1.2

1.2

1.2

1.2

1.2

 3TC

6.7

18.0

39.0

50.3

56.7

59.9

61.5

62.3

62.7

62.9

63.0

63.1

63.1

63.1

63.1

63.1

63.1

63.1

63.1

 LtD/Hbe−

1.1

3.3

7.4

9.6

10.8

11.4

11.8

11.9

12.0

12.0

12.1

12.1

12.1

12.1

12.1

12.1

12.1

12.1

12.1

 LtD/Hbe +

5.0

11.3

22.9

29.1

32.7

34.4

35.3

35.8

36.0

36.1

36.1

36.2

36.2

36.2

36.2

36.2

36.2

36.2

36.2

Values are expressed as %

The rates of response developing during therapy and the data were obtained from the paper published by Marcellin et al., and the assumptions were used for the response rates for 48 weeks of therapy for Tenofovir [17]. The response data of Entecavir treatment for 48 weeks were obtained from the study published by Arnold et al. [18]. The Lamivudine response data were obtained from the publications of Yuan et al. and Lai et al. [19, 20]. The Telbuvidin resistance data were obtained from the data of Lai et al. All assumptions and selected articles for modeling were based on three experts’ opinions.

Cost calculation

The cumulative treatment cost was calculated by including the costs of medicines, tests/follow ups, and complications. The costs paid by the Social Security Institution (SSI) on September 1, 2014 were taken for the calculation of the costs of medicines and tests/follow ups. The average annual costs of the treatment strategies included in the model according to the costs paid by the published figures are shown in Table 4. An annual 3 % discount rate was used for the calculation of the costs over the 40-year model process [21]. It was assumed that the discount rate covered the inflator and deflator effect.
Table 4

Treatment strategies for chronic hepatitis B in Turkey and the annual treatment costs

Medicines

Dose

Unit

Dose (mg/tablet)

Package (tablet/box)

The average annual public

Cost of treatment (TL)

3TC

100

mg/day

100

28

839.94

ETV

0.5

mg/kg/day

0.5

30

3497.53

TDF

300

mg/day

300

30

2236.42

LdT

600

mg/day

600

28

2033.61

The complication costs were taken from the study published in 2009 [22, 23]. The data of 2014 were obtained by adapting the 2009 costs to a 3 % discount rate [21] (Table 5). The transition risks according to the plasma HBV DNA levels and the inter-transition of the complications and the mortality rates were taken from the published studies in the application of the complication costs to the treatment strategies [1117, 19, 2426].
Table 5

The average annual costs of disease conditions in Turkey

Disease states

Original costs (TL/year)

Year

2009 (TL)

2014a (TL)

Compensated cirrhosis

6778

7857

Decompensated cirrhosis

7573

8780

Hepatocellular carcinoma

31,044

35,989

a2014 costs were calculated by using 3 % reduction ratio according to 2009

Calculation of clinical effectiveness

Years of life lost (YLL) was used for the clinical effectiveness parameter. The life expectancy of healthy individuals according to the life expectancy at birth in Turkey was used for the response to therapy, and it was calculated again for each year in the model [27]. In the case of irresponsiveness to therapy, published complications and mortality transitions were used for the calculation of the YLL, and it was calculated again for each year in the model [11, 12, 14, 16, 19, 2226].

Comparison of overall cost and clinical effectiveness

The calculated cumulative treatment cost and clinical effectiveness outcomes were compared according to 5, 10, 20, 30, and 40 years of data calculated in the model.

Comparison of cost-effectiveness

The incremental cost-effectiveness ratio (ICER) was used for the comparison of cost-effectiveness. The costs were sorted from minimum to maximum for the ICER calculation. An assessment was performed between the second leading minimum cost and the maximum cost. If a treatment cost was lower than the next treatment cost and its effectiveness was higher, it was stated to be “superior,” and the assessment was performed with the next treatment. If the effectiveness was high along with a high cost, the ICER formulation was applied as follows [27]:
$${\text{ICER}} = \frac{{{\text{ Total Cost}_{\text {Anti-Viral 1}}}{-}{\text{ Total Cost}_{\text {Anti-Viral 2}}}}}{{{\text{Clinical effectiveness}_{\text {Anti-Viral 1}}} {-}{\text{ Clinical Effectiveness}_{\text {Anti-Viral 2}}}}}$$

The cumulative treatment cost (medicines, tests/follow ups, and complications) was calculated at the end of 40 years, which is the model year, and the YLL was used for the comparison of cost effectiveness.

Sensitivity analysis

The sensitivity analysis was conducted to show the impact of the change of the parameters on the cost-effectiveness ratio. A 25 % increase and decrease of the inputs method was used for the analysis [28].

Results and discussion

The treatment strategies were determined and analyzed for Tenofovir (TDF), Entecavir (ETV), switching to Tenofovir from Entecavir (ETV-TDF), Lamivudine (3TC), switching to Tenofovir from Lamivudine (3TC-TDF), Telbivudine (LdT), and switching to Tenofovir from Telbivudine (LdT-TDF).

Comparison of overall cost and clinical effectiveness

While the minimum years of life lost was found to be 0.22 with TDF treatment for 5 years, the treatment cost was calculated as 12,169 TL. These values were identified as 0.56 years and 7727 TL and 0.37 years and 12,770 TL, respectively, for the 3TC and LdT treatments.

The maximum years of life lost and the treatment cost with the 3TC treatment were identified as 1.60 years and 18,813 TL, and, secondly, 0.89 years and 24,007 TL for the 3TC-TDF treatment for 10 years. The years of life lost and the treatment costs are 0.78 years and 26,848 TL, 1.01 years and 27,295 TL, 0.57 years and 35,918 TL, 0.57 years and 35,918 TL for the other treatment alternatives LdT-TDF, LdT, ETV, and ETV-TDF, respectively. The minimum years of life lost and cost are 0.54 year and 35,821 TL for the TDF treatment for 10 years (Table 6).
Table 6

Years of life lost and treatment costs for each 10 years per capita

Treatments

Year 10

Year 20

Year 30

Year 40

YLL

Total cost (TL)

YLL

Total cost (TL)

YLL

Total cost (TL)

YLL

Total cost (TL)

TDF

0.54

24,948

1.21

52,839

1.73

84,149

2.06

119,604

3TC-TDF

0.89

24,007

1.91

54,785

2.70

90,517

3.20

132,157

LdT-TDF

0.78

26,848

1.77

58,542

2.56

95,357

3.05

138,182

3TC

1.60

18,813

3.81

49,974

5.50

92,666

6.52

147,245

LdT

1.01

27,295

2.37

61,448

3.44

102,458

4.10

151,059

ETV-TDF

0.57

35,821

1.25

74,366

1.79

116,074

2.13

161,642

ETV

0.57

35,918

1.25

74,592

1.79

116,425

2.13

162,115

The minimum years of life lost and the cost were determined as 1.21 years and 52,839 TL for the TDF treatment strategy for 20 years. The years of life lost and the cost for the other treatment strategies, ETV, ETV-TDF, LdT-TDF, 3TC-TDF, LdT, and 3TC, are 1.25 years and 74,592 TL, 1.25 years and 74,367 TL, 1.77 years and 58,542 TL, 1.91 years and 54,785 TL, 2.37 years and 61,448 TL, and 3.81 years and 49,974 TL, respectively.

Over a 30-year period, the TDF treatment was found to have the minimum years of life lost (1.73 years) and the minimum cost (84,149 TL). The years of life lost and the treatment costs are 1.79 years and 116,425 TL for ETV, 1.79 years and 116,074 TL for ETV-TDF, 5.50 years and 92,666 TL for 3TC, 2.70 years and 90,517 TL for 3TC-TDF, 3.44 years and 102,458 TL for LdT, and 2.56 years and 95.357 T for LdT-TDF (Table 6).

When the results of the 40-year period were analyzed, the years of life lost and costs are 2.06 years and 119,604 TL, 2.13 years and 162,115 TL, 2.13 years and 161,642 TL, 6.52 years and 147,245 TL, 3.20 years and 132,157 TL, 4.10 years and 151,059 TL, and 3.05 years and 138,182 TL for TDF, ETV, ETV-TDF, 3TC, 3TC-TDF, LdT, and LdT-TDF, respectively (Table 6).

Comparison of cost-effectiveness

According to the 40-year treatment model designed for an incremental cost-effectiveness comparison, the TDF treatment dominated the alternative treatment strategies, as it provided the minimum total cost and the minimum years of life lost. In other words, TDF was determined to be the most cost-effective treatment strategy compared to the other treatment strategies (Table 7).
Table 7

Incremental cost effectiveness analysis of chronic hepatitis B treatments

Treatments

Total cost (TL)

YLL

Cost difference (TL)

Year difference

ICER

TDF

119,604

2.06

   

ETV-TDF

161,642

2.13

42,037

0.07

Dominated

ETV

162,115

2.13

42,511

0.07

Dominated

LdT-TDF

138,182

3.05

18,577

0.99

Dominated

3TC-TDF

132,157

3.20

12,552

1.14

Dominated

LdT

151,059

4.10

31,455

2.04

Dominated

3TC

147,245

6.52

27,640

4.56

Dominated

Calculations were done according to the constructed 40-year treatment model

In Table 6, the minimum treatment cost belongs to TDF with 119,604 TL in the total cost and drug cost comparison. The drug cost is 84,885 TL for the TDF treatment. The total treatment cost is 147,244 TL, and the drug cost is 28,151 TL for the 3TC treatment.

Sensitivity analysis

The sensitivity analysis was conducted for 25 % varying for each parameters. The most effective parameter for cost-effectiveness was observed as a virologic respond.

In all scenarios of the sensitivity analysis, it was shown that TDF has the lowest cost and the highest effectiveness. Based on these results, TDF dominated all options in all scenarios (Tables 8, 9).
Table 8

25 % varying impact on TDF outcomes

 

Age

HBeAg (−) rate (%)

TDF: virologic response 48th week in HBeAg (−) (%)

TDF: virologic response 48th week in HBeAg (+) (%)

TDF annual drug cost (TL)

Base case

40

70

93.2

76.1

2236

25 % increase

50

88

100.0

95.2

2796

25 % decrease

30

53

69.9

57.1

1677

Table 9

Sensitivity analysis results for the impact of each parameter on cost-effectiveness

Parameter

Change

New value

 

Total cost (TL)

YLL

Cost difference (TL)

Year difference

 

Age = 50 years

 

50

TDF

119,604

1.302

   
   

ETV-TDF

161,642

1.347

42,037

0.045

 
   

ETV

162,115

1.347

42,511

0.046

 
   

LdT-TDF

138,182

1.923

18,577

0.622

 
   

3TC-TDF

132,157

2.028

12,552

0.726

 
   

LdT

151,059

2.581

31,455

1.280

 
   

3TC

147,245

4.109

27,640

2.807

 
   

TDF

119,604

2.987

   
   

ETV-TDF

161,642

3.088

42,037

0.101

 
   

ETV

162,115

3.089

42,511

0.102

 

Age = 30 years

 

30

LdT-TDF

138,182

4.429

18,577

1.442

 
   

3TC-TDF

132,157

4.621

12,552

1.634

 
   

LdT

151,059

5.954

31,455

2.967

 
   

3TC

147,245

9.453

27,640

6.465

 
   

TDF

119,411

2.025

   
   

ETV-TDF

161,353

2.079

41,943

0.054

 
   

ETV

161,826

2.079

42,416

0.055

 

HBeAg (−) rate

25 % increase

88 %

LdT-TDF

132,215

2.656

12,804

0.631

 
   

3TC-TDF

127,731

2.907

8320

0.882

 
   

LdT

137,643

3.152

18,233

1.128

 
   

3TC

128,004

5.124

8593

3.099

 
   

TDF

119,798

2.096

   
   

ETV-TDF

161,930

2.183

42,132

0.087

 
   

ETV

162,404

2.183

42,606

0.088

 

HBeAg (−) rate

25 % decrease

53 %

LdT-TDF

144,149

3.445

24,351

1.349

 
   

3TC-TDF

136,582

3.487

16,784

1.391

 
   

LdT

164,475

5.045

44,677

2.949

 
   

3TC

166,486

7.907

46,688

5.811

 
   

TDF

119,573

2.055

   
   

ETV-TDF

161,642

2.131

42,068

0.076

 
   

ETV

162,115

2.131

42,542

0.076

 

TDF: virologic response 48th week in HBeAg (−)

25 % increase

100.0 %

LdT-TDF

138,176

3.049

18,603

0.994

 
   

3TC-TDF

132,148

3.196

12,574

1.140

 
   

LdT

151,059

4.099

31,486

2.043

 
   

3TC

147,245

6.515

27,672

4.460

 
   

TDF

119,711

2.078

   
   

ETV-TDF

161,642

2.131

41,931

0.053

 
   

ETV

162,115

2.131

42,404

0.053

 

TDF: Virologic response 48th week in HBeAg (−)

25 % decrease

69.9 %

LdT-TDF

138,202

3.054

18,491

0.976

 
   

3TC-TDF

132,186

3.202

12,475

1.124

 
   

LdT

151,059

4.099

31,348

2.021

 
   

3TC

147,245

6.515

27,534

4.437

 
   

TDF

119,538

2.049

   
   

ETV-TDF

161,642

2.131

42,103

0.082

 
   

ETV

162,115

2.131

42,577

0.082

 

TDF: Virologic response 48th week in HBeAg (+)

25 % increase

95.2 %

LdT-TDF

138,153

3.044

18,614

0.996

 
   

3TC-TDF

132,118

3.190

12,580

1.141

 
   

LdT

151,059

4.099

31,521

2.050

 
   

3TC

147,245

6.515

27,707

4.467

 
   

TDF

119,671

2.072

   
   

ETV-TDF

161,642

2.131

41,971

0.059

 
   

ETV

162,115

2.131

42,444

0.060

 

TDF: Virologic response 48th week in HBeAg (+)

25 % decrease

57.1 %

LdT-TDF

138,211

3.056

18,540

0.985

 
   

3TC-TDF

132,195

3.204

12,524

1.133

 
   

LdT

151,059

4.099

31,388

2.027

 
   

3TC

147,245

6.515

27,574

4.444

 
   

TDF

140,826

2.060

   
   

ETV-TDF

161,879

2.131

1053

0.070

 
   

ETV

162,115

2.131

1289

0.071

 

TDF annual drug cost

25 % decrease

2796 TL

LdT-TDF

144,943

3.050

4117

0.990

 
   

3TC-TDF

147,174

3.197

6348

1.137

 
   

LdT

151,059

4.099

0233

2.038

 
   

3TC

147,245

6.515

6419

4.455

 
   

TDF

98,383

2.060

   
   

ETV-TDF

161,405

2.131

63,022

0.070

 
   

ETV

162,115

2.131

63,732

0.071

 

TDF annual drug cost

25 % decrease

1677 TL

LdT-TDF

131,421

3.050

33,038

0.990

 
   

3TC-TDF

117,139

3.197

18,756

1.137

 
   

LdT

151,059

4.099

52,676

2.038

 
   

3TC

147,245

6.515

48,862

4.455

 

Tenofovir dominates all comparisons in all scenarios

Conclusions

Currently, CHB treatment has achieved positive results regarding a high virologic response and a low resistance [4]. All published current guidelines recommend Tenofovir and Entecavir as the first drug for CHB treatment.

In the study conducted in Taiwan and published by Veenstra et al. [29], a life-long Markov model was used, and Entecavir monotherapy was found to be more cost-effective compared to Lamivudine and Adefovir disoproxil combination treatments. In this analysis, Tenofovir monotherapy was found to be the most cost-effective treatment during the first 5 years, the first 10 years, for 30 years, and for 40-year life spans, which is similar to the results of the life span assessment.

In a disease burden study about HBV conducted in Vietnam and published in 2008, the average annual HBV disease cost was determined as $450.35 for this country [30]. In research conducted in China and published in 2013, the cost of CHB was found to be $4.136 [31]. In another study conducted in the US, the average life span cost per capita of HBV was estimated as $2.667 [32]. In a cost analysis of immigrants using the 2006 data in Canada, the treatment costs of Entecavir, Tenofovir, Lamivudine, and pegylated interferon (48 weeks) were determined as $6.504, $5.032, $1.516, and $10.185, respectively [33].

In a hospital-based CHB and CHC treatment cost study evaluating 284 patients in the Denizli province in Turkey, it was found that the treatment cost and total cost were higher with the Entecavir treatment compared to the Tenofovir and Lamivudine treatments. PEG Int-2a and 2b treatments had a higher cost than Lamivudine, Entecavir, Tenofovir treatments, and no treatment [34].

In an analysis including the US, Germany, and some Asian countries conducted by Lui et al. [35], the most cost-effective treatment was found to be Entecavir and Tenofovir monotherapies among switching from Telbivudine and Lamivudine monotherapies to Tenofovir and Entecavir treatments.

In other studies, Tenofovir was reported to be the most cost-effective treatment among Tenofovir, Entecavir, Telbivudine, and Adefovir treatments [35, 36].

There are limitations of this study as assumptions. All assumptions and articles that were used in the study were taken from three experts’ opinions.

In the model presented in this study used for the cost-effectiveness analysis of CHB treatments, Tenofovir was found to be one of the cost-effective methods in comparison with other treatment strategies at different time intervals. In addition to this achievement, Tenofovir has been shown to reduce the cumulative treatment cost in the first line of CHB treatment when compared to a 40-year cumulative treatment cost.

In addition, the sensitivity analysis showed that the most effective parameter is the virologic respond; however, TDF had the lowest cost and the highest effectiveness rates as a cost-effective option in all scenarios.

In conclusion, it could be stated that Tenofovir provides cost-effective results regarding public costs and sustainable health financing by being included in the reimbursement for the first line of CHB treatment both in less years of life lost and the reduced cumulative treatment cost.

Abbreviations

CHB: 

chronic hepatitis B

HBV: 

hepatitis B virus

SUT: 

Healthcare Implementation Notification

YPLL: 

Years of Potential Life Lost

ICER: 

incremental cost-effectiveness ratio

HBsAg: 

hepatitis B surface antigen

CI: 

confidence interval

3TC: 

lamivudine

LdT: 

telbivudine

ETV: 

Entecavir

TDF: 

Tenofovir

ETV-TDF: 

switching to tenofovir from entecavir

LdT-TDF: 

switching to tenofovir from telbivudine

3TC-TDF: 

switching to tenofovir from lamivudine

SSI: 

Social Security Institution

YLL: 

years of life lost

Declarations

Authors’ contributions

GK helped to design the health economics model and prepare the article. AK helped to review the literature and prepare the article. FBY helped to review the literature and prepare the article. OO helped to design the health economics model. EK helped to review the literature. All authors read and approved the final manuscript.

Competing interests

The analysis was conducted under Gilead Sciences Turkey`s unconditional sponsorship. Guvenc Kockaya, Akın Kose and Ece Kucuksayrac are the employee of Gilead Science Turkey. Oktay Ozdemir is the health economics and modeling consultant of Gilead Science Turkey. Fatma Betul Yenilmez is contractor consultant of Gilead Science Turkey.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Gilead Sciences Turkey
(2)
Akıl Consultancy
(3)
Yorum Consultancy

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Copyright

© Kockaya et al. 2015

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