Cost-effectiveness Analysis Of Nucleos(t)ide Analogue Monotherapies And Initial Combination Treatment For Chinese HBeAg-positive Chronic Hepatitis B Patients

Background:Chronic hepatitis B(CHB) is a major global public health problem. Although current nucleos(t)ide analogues can suppress the replication of HBV DNA, the cost of long-term therapy may result in the financial burden for CHB patients. However, no pharmacoeconomic study yet testthe nucleos(t)ide analogue monotherapies and initial combination treatment strategies. Objective: 1. Conducted the cost-effectiveness analysis of the current treatment strategies(includinginitial nucleos(t)ide analogue monotherapies and subsequent rescue treatments) forHBeAg-positive patients in China. 2. Evaluated the long-term cost-effectiveness of lamivudine(LAM) plus adefovir(ADV)combination treatment. Methods:From the Chinese healthcare perspective, a Markov model was applied to simulate the disease progression of CHB, and evaluated the long-term cost-effectiveness associated with 19 nucleos(t)ide analogue monotherapy strategies and 6 initial LAM+ADV combination treatment strategies. The parameters(transition rates, costs and QALYs) used in the model were derived from published studies. The cumulative life-time(40-year time span) costs, life years saved(LYS) and quality-adjusted life years(QALYs) was used as the outcome measures, and calculated the cost-effectiveness ratio(CER) and incremental costeffectiveness ratio(ICER) for each strategy. Two different rescue strategies were administered for patients with second-line treatment failure(base-case analysis: maintain the original rescue strategy; scenario analysis: ETV+TDF combination treatment). Additionally, branded and generic drug prices were separately analyzed in the model. One-way and probabilistic sensitivity analysis were used to explore model uncertainties. Results:The three strategies, including the initial use of ETV monotherapy then switching to LAM+ADV, TDF, or ETV+TDF,were all on the cost-effectiveness frontier, and thus they were not economically dominated by other options. Compared to the LAM then ADV(lowest lifetime cost), the incremental cost-effectiveness ratios(ICERs) of these three strategies were all lower than the willingness-to-pay(WTP) threshold of 139,594 Chinese Yuan(CNY)/QALY. The ETV then ETV+TDF has generated the highest QALYs, however, as compared to the ETV then TDF(the second-mosteffective treatment), the ICERs were 2,112,550CNY/QALY and 1,518,367CNY/QALY for branded and generic drugs, respectively. The probabilistic analysisalso showed that the ETV then TDFwas the preferred option for the treatment of CHB patients, as showed in the cost-effectiveness acceptable curves.For the initial LAM+ADV combination therapies, LAM+ADV then ETV+TDF achieved the highest LYS and QALYs, but also generated the highest life-time cost. Compared to the reference strategy(ETV then LAM+ADV, which generated the lowest lifetime cost), the ICERs of LAM+ADV then ETV+TDF were far higher than the WTP threshold(branded drug: 272,988 CNY/QALY; generic drug: 238,188 CNY/QALY). However, among all the treatment strategies, the ICERs of the strategy of ETV then TDF were lowest versus reference treatment(branded drug: 65,051 CNY/QALY; generic drug: 92,586 CNY/QALY). Furthermore, ETV then TDF was directly dominated(less cost and more efficacy) the other strategies of initial LAM+ADV combination therapies. Conclusion:For both nucleos(t)ide analogue monotherapies and initial combination treatment strategies, ETV then TDF was still the most cost-effective option for the treatment of Chinese HBeAg-positive patients.