直接抗病毒藥物用於臺灣C型肝炎第一型且曾治療失敗病人 之成本效益分析

Abstract

研究背景: 2011 年起，美國食品藥物管理局(U.S. Food and Drug Administration, FDA) 開始核准了一系列直接抗病毒藥物，用於治療C 型肝炎。在國外臨床試驗的數據顯示，此類藥物比上目前的C 型肝炎標準療法-聚乙二醇干擾素加上雷巴威林(peginterferon plus ribavirin, PR) 對於C 型肝炎的療效較佳。目前直接抗病毒藥物皆尚未納入健保給付，而直接抗病毒藥物們高昂的藥價，需要再更多的研究評估是否它們值得納入健保給付。 研究目的: 此研究評估以下四種含直接抗病毒藥物的療法用於臺灣地區之前治療失敗的C型肝炎第一型病人，比上目前的標準C 型肝炎療法(PR)是否具有成本效益:博賽波維加上聚乙二醇干擾素和雷巴威林(boceprevir and peginterferon plus ribavirin, BOC+ PR)、思美匹維加上索非布維(simeprevir+ sofosbuvir, SMV+SOF)、索非布維加上雷迪帕維(sofosbuvir/ledipasvir, SOF+LDV)以及歐比它維、佩利它匹維、利托納維此三種藥物組成的複方錠劑加上達沙逼維和雷巴威林(ombitasvir/paritaprevir/ritonavir+ dasabuvir and ribavirin, AOD+RBV) 方法: 本研究為成本效果分析(cost-effectiveness analysis)，採用健保署觀點及折現率為3%，使用馬可夫模型 (Markov model)來模擬C 型肝炎之肝病病程，以推估符合治療條件之五十歲病人的終身醫療成本與效果。由於直接抗病毒藥物大部分尚未獲得健保給付，無法取得台灣市場價格的藥品由美國藥價估計之，並進行單維及機率性敏感度分析評估結果之不確定性。 結果: 模型模擬之結果顯示，各組治療臺灣C 型肝炎第一型且曾治療失敗病人每人平均存活人年數(life-years)及品質校正生活年(QALYs)如下: BOC+ PR: 18.16 life-years/ 16.67 QALYs; AOD+RBV: 19.72 life-years/ 18.41 QALYs; SOF+LDV: 19.73 life-years/ 18.43 QALYs; SMV+SOF: 19.53 life-years/ 18.22 QALYs。而相較於目前C型肝炎標準療法(PR)的遞增成本效益比值(ICER)如下: BOC+ PR, 324,416 NTD/QALY; AOD+RBV, 721,381 NTD/QALY; SOF+LDV, 803,281 NTD/QALY, SMV+SOF 1,571,000 NTD/QALY。 結論: 在本研究中的基礎方案中，假設遞增成本效益比值之閾值為臺灣之一倍人均GDP(NT$62, 3871)時，可稱BOC+PR 此療法具有成本效益。而在無干擾素療法(peginterferon free therapies)中, 此三種療法比上目前標準療法的遞增成本效益比值皆超過臺灣之一倍人均GDP。但目前台灣尚未對遞增成本效益比值之閾值有所共識，故含直接抗病毒藥物的療法是否具有成本效益尚待討論。此外，未來還需更多財務衝擊等研究，以便 政策制定者參考。

Background A new era in hepatitis C treatment has emerged since the approval of some direct acting antivirals (DAAs) in the U.S. from 2011. Evidence from randomized controlled trials of DAA-based therapies shows higher efficacy than current standard of care(peginterferon plus ribavirin). DAAs are not reimbursed by National Health Insurance (NHI) in Taiwan yet. Despite of high efficacy of DAAs, their high acquisition costs may cause concerns for reimbursement in Taiwan. Objective This study aims to evaluate the cost-effectiveness of four kinds of DAAs-containing regimens (BOC+ PR, boceprevir and peginterferon plus ribavirin; SMV+SOF, simeprevir+ sofosbuvir; SOF+LDV, sofosbuvir/ledipasvir; AOD+RBV, ombitasvir/paritaprevir/ritonavir+ dasabuvir and ribavirin) by comparing with current standard of care (PR) for previous treatment-failure HCV genotype 1 patients in Taiwan. Methods A Markov model was developed to simulate progression of hepatitis C infection and to estimate the long-term health outcomes, quality-adjusted-life-years (QALYs), life-time costs of per HCV patient. Age of the treatment eligible hypothetical cohort was 50 years old. Due to lack of the NHI-reimbursed price of the four DAAs, drug costs were estimated by current market prices in Taiwan or wholesale acquisition costs in America. Time horizon was set to be life-time. We adopted the payer’s perspective and considered only direct medical costs. One-way sensitivity analysis and probabilistic sensitivity analysis were also carried out to account for uncertainty. Results In the treatment-failure HCV genotype 1 patients in Taiwan, the DAAs therapies increased the total long-term health outcomes and QALYs compared with PR. (BOC+ PR: 18.16 life-years/ 16.67 QALYs; AOD+RBV: 19.72 life-years/ 18.41 QALYs; SOF+LDV: 19.73 life-years/ 18.43 QALYs; SMV+SOF: 19.53 life-years/ 18.22 QALYs). The respective incremental cost effectiveness ratio compared to PR: BOC+ PR, 324,416 NTD/QALY; AOD+RBV, 721,381 NTD/QALY; SOF+LDV, 803,281 NTD/QALY, SMV+SOF 1,571,000 NTD/QALY. Conclusions In this study, the BOC+PR therapy is cost-effective compared to PR in the base case under the threshold of 1 GDP per capita in Taiwan (1 GDP per capita =NT$623,871). The ICERs of interferon free regimens are higher than 1 GDP per capita. There is no consensus of ICER threshold in Taiwan yet, whether the DAAs therapies are cost-effective or not still waits for consensus. In addition, we recommend that more research like budget impact are needed for policy makers.