| 摘要: | 研究背景
近年研發出的長效型第八凝血因子用於治療嚴重A型血友病患者，可以減少預防性凝血因子治療的給藥頻率，也可以維持較高的凝血因子低谷濃度。
研究主旨
分析跟標準型第八凝血因子相比，兩種長效型第八凝血因子(rFVIII-Fc及PEG-rFVIII)用於預防性凝血因子治療，由台灣全民健康保險觀點來檢視是否具有成本效益。
研究方法
本研究結合決策樹模型以及三個健康狀態的馬可夫模型，三個健康狀態分別為沒有目標關節、有目標關節、死亡。長效型及標準型第八凝血因子的健康效果由臨床試驗及在台灣的觀察性研究的文獻中蒐集，要擷取的健康效果包括：年度出血次數、目標關節數量、及凝血因子使用量。目標關節及年度出血次數會造成健康效用的減損，較低的輸注頻率則會造成健康效用的增加。用於預防性凝血因子治療及治療出血事件的凝血因子的花費皆會被計算。使用遞增成本效果比值（ICER）來計算每得到一單位的品質調整生命年數（QALY）需要花費多少，以評估治療選項比較之後的成本效益。單因子敏感度分析及機率性敏感度分析皆會用以評估分析結果的穩健性。
研究結果
基礎值分析的結果顯示，跟標準型第八凝血因子相比，rFVIII-Fc會增加新台幣63,016,954元的花費以及增加4.34個QALY，得到的ICER為每單位QALY需要花費新台幣14,534,522。跟rFVIII-Fc相比的話PEG-rFVIII則是絕對劣勢。單因子敏感度分析顯示，效用比重跟預防性凝血因子使用量為影響分析結果的重要因子。機率性敏感度分析顯示跟標準型第八凝血因子相比，rFVIII-Fc與PEG-rFVIII具成本效益的機率很低。
研究結論
此研究發現，以台灣全民健康保險觀點、並以一到三倍的台灣人均國內生產毛額作為閾值來評估，用於預防性凝血因子治療的長效型第八凝血因子跟標準型第八凝血因子相比，為不具成本效益的治療選項。建議未來研究可納入年度出血次數、凝血因子使用量及關節健康成效的真實世界證據，以優化成本效用分析模型。
Background
Extended half-life (EHL) factor VIII has been developed in recent years to reduce the dosing frequency of prophylaxis and to maintain higher factor trough levels for bleeding prevention in patients with severe hemophilia A.
Objectives
To examine the cost-effectiveness of the prophylactic use of EHL factor VIII (FVIII) products, rFVIII-Fc and PEG-rFVIII, compared to standard half-life (SHL) FVIII in patients with severe hemophilia A from the perspective of the National Health Insurance in Taiwan.
Methods
A combination of a decision tree and a three-state Markov model was adopted, including no target joint (TJ), TJ, and dead states. The health effects of EHL FVIII and SHL FVIII were retrieved from clinical trials and real-world data in Taiwan, including annualized bleeding rate (ABR), TJ, and factor consumption. The utility decrement of TJs and bleeding episodes as well as the utility increment of decreased frequency of infusion were accounted for. The costs of factor consumption for prophylaxis and for treating bleeding events were calculated. The incremental cost-effectiveness ratio (ICER) was calculated and presented as costs per quality-adjusted life year (QALY) to compare the cost-effectiveness of EHL FVIII and SHL FVIII. One-way sensitivity analyses and probabilistic sensitivity analyses (PSA) were conducted to test the robustness of the results.
Results
The base-case analysis demonstrated that compared to SHL FVIII, rFVIII-Fc had a cost increase of NTD 63,016,954 and a QALY gain of 4.34, yielding an ICER of NTD 14,534,522 per QALY while PEG-rFVIII was dominated by rFVIII-Fc. One-way sensitivity analysis showed that utility weights and factor consumption of prophylaxis were key drivers of the results. The PSA results showed that the probability of rFVIII-Fc and PEG-rFVIII being cost-effective when compared to SHL FVIII was low.
Conclusion
Our findings suggest that the prophylactic use of EHL FVIII products may not be cost-effective compared to low-to-intermediate dose SHL FVIII using the threshold of 1 to 3 times GDP per capita in Taiwan. Future research incorporating real-world evidence of ABR, factor consumption, and joint health outcomes can help optimize the model for the evaluation of EHL FVIII products. |
