Cost-effectiveness analysis of different rescue therapies in patients with lamivudine-resistant chronic hepatitis B in China

Abstract

Background: Several rescue therapies have been used in patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB); however, the economic outcome of these therapies is unclear. The object of the current analysis was to evaluate the lifetime cost-effectiveness of rescue therapies among patients with LAM-resistant CHB.

Methods: A Markov model was developed to simulate the clinical course of patients with LAM-resistant CHB. From the perspective of Chinese health care, a lifetime cost-utility analysis was performedfor 4 rescue strategies: adefovir (ADV), entecavir (ETV) or tenofovir (TDF) monotherapy and combination therapy using LAM and ADV. A hypothetical cohort of 45-year-old patients with genotypic or clinical LAM-resistant CHB entered the model, and the beginning health state was LAM-resistant CHB without other complications. The transition probabilities, efficacy and resistance data for each rescue therapy as well as the costs and utility data were estimated from the literature. The discount rate (3%) utilized for costs and benefits. Sensitivity analyses were used to explore the impact of uncertainty on the results.

Results: In LAM-resistant HBeAg-positive and HBeAg-negative CHB cohorts, TDF monotherapy and combination therapy were on the efficiency frontier for both positive and negative populations. Compared with no treatment, the use of combination therapy cost an additional $6,531.7 to gain 1 additional quality-adjusted life year (QALY) for HBeAg-positive patients and $4,571.7 to gain 1 additional QALY for HBeAg-negative patients. TDF monotherapy for HBeAg-positive patients, shows greater increase in QALYs but higher incremental cost-effectiveness ratio (ICER) in comparison with combination therapy. In probabilistic sensitivity analyses, combination therapy was the preferred option for health care systems with limited health resources, such as Chinese health care system.

Conclusion: In Chinese patients with LAM-resistant CHB, combination therapy is a more cost-effective option than the competing rescue therapies.

Figure 1

Markov diagram of the LAM-resistant CHB disease model. The ovals represent the eight mutually exclusive health states that the patient with LAM-resistant CHB might experience over a lifetime. Patients begin in the “lamivudine-resistant CHB” state and might transit between states or remain in their current health state during each 1-year cycle.

Figure 2

Cost-effectiveness of rescue therapies for LAM-resistant HBeAg-positive (A) and HBeAg-negative (B) chronic hepatitis B. The x-axis indicates the discounted lifetime quality-adjusted life-years (QALYs) for each therapy, and the y-axis indicates the total discounted lifetime costs (US dollar). The oblique line connects “no treatment” and the most cost-effective therapies; therapies above the straight lines were dominanated. Combination strategy uses LAM and ADV.

Figure 3

Tornado diagram representing the net health benefit (QALYs, WTP=$11,034) determined by a one-way sensitivity analysis of combination therapy (ADV+LMV) vs. no treatment for LAM-resistant HBeAg-positive (A) and HBeAg-negative (B) chronic hepatitis B. The vertical line represents the base-case value for the net health benefit under WTP=$11,034.

Figure 4

Scenario and two-way sensitivity analysis. The impact of age at initiation of LAM resistance on the incremental cost-effective ratio (ICER) of rescue therapies in comparison with “no treatment” for LAM-resistant HBeAg-positive (A) and HBeAg-negative (B) chronic hepatitis B: the x-axis indicates the age at initial rescue therapy, the y-axis indicates the ICER ($ per additional QALY), the bold horizontal two-dash and solid lines represent the thresholds for China and Shanghai City, respectively. Varying the TDF cost and efficacy leads to different incremental cost-effective ratio (ICER) of TDF monotherapy over “no treatment” for LAM-resistant HBeAg-positive (C) and HBeAg-negative (D) chronic hepatitis B: the x-axis indicates the different cost of TDF, the y-axis indicates the different efficacy of TDF (the ratio relatively to the current using values in the base-case analysis), the bold oblique lines represent that the ICERs for TDF strategy were equal to combination strategy, and grey and white areas indicates the ICERs for TDF strategy were higher and lower than combination strategy, respectively. Combination strategy uses LAM and ADV.

Figure 5

Probabilistic results of the incremental cost-effectiveness differences between treatment with combination therapy (ADV+LMV) and with (A) no treatment, (B) ADV monotherapy, (C) ETV monotherapy and (D) TDF monotherapy for a cohort of 1,000 LAM-resistant HBeAg-positive and HBeAg-negative chronic hepatitis B patients. The y-axis represents the incremental costs. The x-axis represents the incremental quality-adjusted life years (QALYs) gained. Dots that lie below the ICER threshold (the oblique lines) reflect simulations in which the cost per additional QALY gained with combination therapy was below the ICER threshold.

Figure 6

Cost-effectiveness acceptability curve for rescue therapies for LAM-resistant HBeAg-positive (A) and HBeAg-negative (B) chronic hepatitis B. The y-axis indicates the probability that a therapy is cost-effective across willingness to pay per QALY gained (x-axis). The bold vertical two-dash and solid lines represent the thresholds for China and Shanghai City, respectively. Combination strategy uses LAM and ADV.