Cost-effectiveness Analysis Of Nucleos(t)ide Analogue Treatments For Chronic Hepatitis B Patients

Background:Chronic hepatitis B(CHB)is a serious infectious disease,which is harmful for public health and brings heavy disease burden on patients and society.The most important way to prevent CHB disease progression is antiviral treament,and the nucleos(t)ide analogues(NAs)are the major drugs of antiviral treatment.Although NAs can suppress the replication of heaptitis B virus,different treatment options will generate various efficacy and costs.However,no pharmacoeconomic study has evaluated the initial NA monotherapies subsequent with rescue therapies or response-guided therapies.Objective: 1.For treatment-na?ve patients,we evaluated the cost-effectiveneess of initial NA monotherapies subsequent with rescue therapies,and identified the optimal treatment option.2.Moreover,we compared the cost-effectiveness between the response-guided therapies of lamivudine(LAM),telbivudine(TBV)and adefovir(ADV)and the opimal treatment option in the first part.Methods:Based on the perspective of Chinese healthcare,we applied the Markov model to simulate the disease progression of CHB patients and evaluated 19 treatment options from initial NA monotherapies subsequent with rescue therapies and 6 treatment options from initial NA monotherapies subsequent with response-guided therapies.All data used in the model were derived from published studies(including natural disease progression rates,virlogical reponse rates,resistance rates,utility of disease states and the costs).The lifetime costs and quality-adjusted life years(QALYs)were used to calculate the cost-effectiveness ratio(ICER)for treatment options.Besides,considering of the situation that generic drugs were available in Chinese market,generic drug prices were also analyzed in scenario analysis.One-way and probabilistic sensitivity analyses were applied to explore model uncertainties.ResultsIn the first part,tenofovir(TDF)monotherapy generated the highest QALYs and became the alternative treatment option.After getting rid of the dominated treatment options,compared with the lower lifetime costs treatment option,the ICERs(HBeAgpositive patients: 8315 CNY/QALY and HBeAg-negative: 14613 CNY/QALY)of TDF monotherapy were far lower than the willing-to-pay threshold(3x per capita gross national product,155594 CNY/QALY,2016).Moreover,the cost-effectiveness accepetable curve showed,at the threshold of 155594 CNY/QALY,TDF monotherapy had the highest probability to be the most cost-effective treatment option(HBeAg-postive patients: 96.9% and HBeAg-negative patients: 92.3%).Based on different type of drug resistance [LAM,TBV,ADV and entecavir(ETV)],we classified the treatment options and did subgroup analysis.On each subgroup,TDF rescue therapy generated the high QALYs(10.79-12.29)and lowest lifetime costs(423505-548857CNY),thus,they were alternative treatment options of each subgroup.Considering of the alternative treatment options of each group,although some rescue therapies achieved better QALYs,the ICER(180300 – 3644300 CNY/QALY)of them were far beyond the threshold of 155594 CNY/QALY.Depended on the effectiveness between TDF monotherapy and ETV then switching to TDF therapy,we explore the drug price of ETV by one-way sensitivity analysis without limit.The results showed that ETV then switching to TDF therapy would be cost-effective when the drug price of ETV dropped to 4199 CNY per year or lower.In the second part,the situation was same to the first part,TDF monotherapy was still the alternative treatment option because of its highest QALYs.Among the alternative treatment options,compared with the LAM roadmap with TDF therapy,the ICER(HBeAgpositive patients: 16866 CNY/QALY and HBeAg-negative patients: 16510 CNY/QALY)of TDF monotherapy was far below the threshold of 155594 CNY/QALY.Combing the first part content,we classfied the treatment options into three subgroups(based on the initial monotherapy with LAM,TBV and ADV).For each subgourp,roadmap with TDF therapy generated the best QALYs,thus,they were alternative options.Among the alterative options,the ICERs of roadmap with TDF therapy were ranging from 9941CNY/QALY to 30260 CNY/QALY,which is still far lower than 155594 CNY/QALY.Furthermore,if the roadmap with TDF therapy was deleted,roadmap with combination therapy was the alternative treatment option.Compared with the other alternative treatment option for each subgroup,the ICERs(ranging from 36489 CNY/QALY to 121054 CNY/QALY)of roadmap with combination therapy were lower the threshold of 155594 CNY/QALY.ConclusionsFor the treatment-na?ve patients or mono drug resistant patients,TDF monotherapy was the most cost-effective treatment option.When drug price of ETV dropped to 4199 CNY per year or lower,ETV then switching TDF therapy would be a cost-effective treatment option.For the patients who applied high resisitant NAs,response-guided therapies were more cost-effective than rescue theraies.