臺灣博碩士論文加值系統

異位性皮膚炎(Atopic Dermatitis)是一種慢性、覆發性、高度搔癢的皮膚發炎疾病，複雜且異質性高，具有多樣化的臨床表徵。異位性皮膚炎的全球盛行率約為7.88%，而根據2020年台灣皮膚科醫學會所公布之數據，台灣盛行率則約為4.1%~6.7%。異位性皮膚炎的第一線治療為潤膚劑、局部皮質類固醇等；第二線治療為局部鈣調磷酸酶抑制劑、光照療法等；而第三線治療即為免疫調節劑等全身性療法。目前常用之第三線藥物為dupilumab，已在台灣經衛生福利部食品藥物管理署核准使用於6個月以上的兒童以及成年中重度異位性皮膚炎病患，並具條件健保給付給6歲以上病患；而具同等治療地位的新藥abrocitinib，已在台灣被核准使用於12歲以上中重度異位性皮膚炎病患，並具條件健保給付給成人病患。
本研究之研究動機主因異位性皮膚炎好發於兒童期，在兒童及青少年族群的盛行率也高於成人族群，目前作為第三線療法的dupilumab在台灣已獲健保給付給兒童及青少年族群病患，而療效相近的abrocitinib在台灣卻僅獲健保給付給成人族群病患，因此本研究欲以台灣衛生福利部中央健康保險署的觀點，分析相較於使用dupilumab作為治療策略，若將abrocitinib的健保給付範圍擴大至青少年族群是否具有成本效益。
本研究採用台灣衛生福利部中央健康保險署觀點，以一個周期為16周、時間範圍為40年的馬可夫模型(Markov model)模擬分別以abrocitinib及dupilumab治療中重度異位性皮膚炎12歲以上青少年至成人病患的情景，並以Microsoft Excel進行成本效益分析，計算兩種治療策略之成本、QALYs以及ICER，並針對模型以及參數的不確定性進行敏感度分析，包括決定性敏感度分析及機率性敏感度分析。
對於中重度異位性皮膚炎之病患，相較於使用dupilumab，使用abrocitinib能夠節省NT$104,567並增加1.57個QALYs，是具有成本效益的，且不論在中度或重度異位性皮膚炎族群中同樣具有成本效益。決定性敏感度分析結果顯示兩種治療策略在模型中的轉移機率變化對ICER值有明顯的影響，而機率性敏感度分析結果顯示對於中重度異位性皮膚炎之病患，使用abrocitinib約有95%的機率一定具有成本效益。

Atopic Dermatitis (AD) is a chronic, relapsing, highly pruritic inflammatory skin disease characterized by its complexity and high heterogeneity, manifesting with diverse clinical symptoms. The global prevalence of AD is approximately 7.88%, while the prevalence in Taiwan, according to data published by the Taiwanese Dermatological Association in 2020, ranges from 4.1% to 6.7%. The first-line treatments for AD include emollients and topical corticosteroids. Second-line treatments consist of topical calcineurin inhibitors and phototherapy, while third-line treatments involve systemic therapies such as immunomodulators. Currently, Dupilumab is a widely used third-line medication, approved by Taiwan's Ministry of Health and Welfare for moderate-to-severe AD in children aged six months and older, as well as adults, with conditional reimbursement for patients aged six years and older. Another new drug with similar therapeutic status, Abrocitinib, has been approved in Taiwan for use in moderate-to-severe AD patients aged 12 years and older, with conditional reimbursement for adult patients.
The motivation for this study arises from the higher prevalence of AD in children and adolescents compared to adults. While Dupilumab, as a third-line therapy, has received insurance coverage for pediatric and adolescent patients in Taiwan, Abrocitinib, despite having similar efficacy, is only reimbursed for adult patients. This study aims to analyze, from the perspective of Taiwan's National Health Insurance Administration (NHIA), the cost-effectiveness of expanding insurance coverage for Abrocitinib to include adolescent patients, compared to using Dupilumab as a treatment strategy.
This study utilizes a Markov model with a 16-week cycle and a 40-year time horizon from the NHIA's perspective to simulate the scenarios of treating moderate-to-severe AD patients aged 12 years and older with either Abrocitinib or Dupilumab. Cost-effectiveness analysis is conducted using Microsoft Excel to calculate the costs, Quality-Adjusted Life Years (QALYs), and Incremental Cost-Effectiveness Ratios (ICERs) of the two treatment strategies. Sensitivity analyses, including deterministic and probabilistic sensitivity analyses, are performed to assess the uncertainties in the model and parameters.
For moderate-to-severe AD patients, using Abrocitinib is cost-effective compared to Dupilumab, saving NT$104,567 and increasing QALYs by 1.57. This cost-effectiveness is observed in both moderate and severe AD patient groups. Deterministic sensitivity analysis indicates that changes in transition probabilities in the model significantly impact ICER values, while probabilistic sensitivity analysis shows that Abrocitinib has approximately a 95% probability of being cost-effective for moderate-to-severe AD patients.

目 錄
中文摘要..................................................................................................i
Abstract ..................................................................................................iii
目 錄....................................................................................................... v
圖目錄..................................................................................................viii
表目錄.................................................................................................... ix
第一章 研究背景 ................................................................................... 1
1.1 異位性皮膚炎............................................................................ 1
1.2 治療方法.................................................................................... 4
1.2.1 第一線治療 ....................................................................... 5
1.2.2 第二線治療 ....................................................................... 7
1.2.3 第三線治療 ....................................................................... 8
1.3 臨床研究證據........................................................................... 10
1.4 研究動機與目的....................................................................... 12
第二章 研究方法 ................................................................................. 13
2.1 研究設計................................................................................... 13
2.2 模型結構................................................................................... 14
2.3 參數來源................................................................................... 16
2.4 分析方法................................................................................... 20
第三章 研究結果 ................................................................................. 23
3.1 中重度異位性皮膚炎病患 ...................................................... 23
3.1.1 成本效益分析................................................................. 23
3.1.2 決定性敏感度分析.......................................................... 24
3.1.3 機率性敏感度分析.......................................................... 26
3.2 中度異位性皮膚炎病患........................................................... 28
3.2.1 成本效益分析................................................................. 28
3.2.2 決定性敏感度分析.......................................................... 29
3.2.3 機率性敏感度分析.......................................................... 31
3.3 重度異位性皮膚炎病患........................................................... 33
3.3.1 成本效益分析 ................................................................. 33
3.3.2 決定性敏感度分析.......................................................... 34
3.3.3 機率性敏感度分析.......................................................... 36
第四章 討論與研究限制...................................................................... 39
4.1 研究結果與討論....................................................................... 39
4.2 研究限制................................................................................... 40
第五章 結論與建議.............................................................................. 42
5.1 結論 .......................................................................................... 42
5.2 未來展望................................................................................... 42
參考文獻............................................................................................... 44
附錄....................................................................................................... 48
圖目錄
圖一、馬可夫模型........................................................................ 16
圖二、中重度異位性皮膚炎單因子敏感度分析.............................. 26
圖三、中重度異位性皮膚炎成本效益平面..................................... 27
圖四、中重度異位性皮膚炎成本效益接受曲線.............................. 28
圖五、中度異位性皮膚炎單因子敏感度分析................................. 30
圖六、中度異位性皮膚炎成本效益平面........................................ 32
圖七、中度異位性皮膚炎成本效益接受曲線................................. 33
圖八、重度異位性皮膚炎單因子敏感度分析................................. 35
圖九、重度異位性皮膚炎成本效益平面........................................ 36
圖十、重度異位性皮膚炎成本效益接受曲線................................. 37
表目錄
表一、研究設計........................................................................... 14
表二、馬可夫模型轉移機率參數................................................... 17
表三、馬可夫模型成本參數.......................................................... 19
表四、馬可夫模型效用參數.......................................................... 20
表五、中重度異位性皮膚炎成本效益分析..................................... 24
表六、中度異位性皮膚炎成本效益分析........................................ 29
表七、重度異位性皮膚炎成本效益分析........................................ 34
表八、成本效益分析結果總覽...................................................... 38

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