類風濕性關節炎患者使用生物製劑治療的果效評估

The Outcome Research of Biological Agents in Taiwanese Rheumatoid Arthritis Patients

張慧貞(Hui-Chen Chang)

指導教授 ： 蔡東榮

高雄醫學大學/藥學院/臨床藥學研究所/碩士(2010年)

摘要

研究背景：類風濕性關節炎為一種慢性發炎性的關節疾病，治療藥物的種類繁多，但因藥效及耐受性的影響，大多無法達到疾病緩解的目的。新一代的生物製劑治療藥已開發上市，但因藥價昂貴，目前健保給付僅限用於嚴重類風濕性關節炎且對傳統治療反應不佳的患者；但生物製劑長期使用的療效與安全性尚未完全確立。因此本研究為針對類風濕性關節炎病人使用生物製劑治療的果效評估，並探討適合測量類風濕性關節炎病人健康相關生活品質影響之工具。
研究方法：本研究分成兩部分：第一部分是漸進地採用區域性的「中央健保局高屏分局之申報檔」（2006至2009年6月）及具全國代表性「全民健康保險學術資料庫之百萬人承保抽樣歸人檔」（2003至2008）分析門診成年類風濕性關節炎病人醫療利用的現狀、生物製劑使用情形及生物製劑的安全性與有效性。
第二部分研究為橫斷面研究，自2009年6月至2009年11月於台灣南部某醫學中心的風濕免疫科門診進行，藉時間交換法、歐洲生活品質量表五個面向問卷及視覺類比尺度法（EQ-5D VAS）實際訪談類風濕性關節炎病人；歐洲生活品質量表五個面向問卷再以日本的加權指標換算所得的效用值（EQ-5D 效用值）。
結果：研究結果顯示類風濕性關節炎病人主要為女性，好發於大於50歲的患者，每月就醫人次以醫學中心最高。使用生物製劑治療的病人相較於未使用者，女性患者比例較高且首次就醫處所集中於醫學中心就診（p < 0.001）。隨著生物製劑每月使用人次上升，生物製劑藥費佔總藥費的比例也逐月上升。大部分的生物製劑之新處方者以etanercept起始治療。與處方生物製劑前30天用藥相較，生物製劑之新處方者處方生物製劑後第30天併用藥物（methotrexate處方量、傳統疾病修飾抗風濕病藥物或非糖皮質類固醇抗發炎藥種類）都明顯比用藥前顯著下降（p < 0.001）。然而，使用etanercept治療的生物製劑之新處方者，與對照組相較，發生感染疾病危險性較高。
總共有79位類風濕性關節炎患者完成訪談，86%受訪者為女性，平均55.23±11.30歲。使用時間交換法評估生活品質之平均效用值為0.58±0.32；使用視覺類比量表之平均效用值為63.66±19.85；EQ-5D效用值平均為0.71±0.18。相較歐洲生活品質量表，時間交換法會受到較多因素（受訪者的疾病活動程度、自我照顧能力、憂鬱、婚姻狀況、每週methotrexate的使用劑量）的影響。
結論：生物製劑之新處方者處方生物製劑短期即可看到顯著的療效，然而，使用etanercept治療相較未使用者會增加病人罹患感染疾病的風險；因adalimumab於2007年下半年才開始有處方記錄，使用adalimumab治療的病人觀察時間較短且人數較少，難以完全觀察其安全性，未來需要有長期追蹤研究來釐清adalimumab與感染事件的關聯性。
EQ-5D 效用值僅受到受訪者的疾病活動程度影響，適宜測量國內類風濕性關節炎受訪者的健康相關生活品質。然因，台灣並未有歐洲生活品質量表已確效的加權方式，建議未來也需要進一步發展台灣地區歐洲生活品質量表確效的加權系統。

關鍵字

類風濕性關節炎 ； 生物製劑 ； 果效 ； 安全性 ； 生活品質 ； 歐洲生活品質量表

並列摘要

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systematic, inflammatory joint disorder. Currently, the innovative, highly expensive biological agents are reserved to treat patients unresponsive to traditional therapy, but the long-term efficacy and safety of biological agents remain unclear. This is a clinical outcome research on biological agents in treating Taiwanese RA patients, and also a case study to explore the adaption of quality-of-life (QoL) measurements for Taiwanese RA patients.
METHODS: The first part of this study used population-based reimbursement database, including the individual claim data from the Kaopin Division of Taiwanese National Health Insurance and the systematic sampled Taiwanese National Health Insurance Research Database, to evaluate the utilization, effectiveness and safety of biological agents in adult RA outpatients.
The second part of this study was a cross-sectional study conducted at a medical center in Southern Taiwan from June to November 2009. Adult RA outpatients were invited for interviews, while health-related quality of life (QoL) was measured by time-trade-off (TTO), Euroqol (EQ-5D) questionnaire and visual analogue scale (EQ-5D VAS). The EQ-5D assessment was transformed into EQ-5D index using Japanese preference weight.
RESULTS: Of all, this study reveals that the majority of RA patients is female, age more than fifty and prefers to access medical centers. Comparing to those never used biological agents, RA patients who used biological agents have higher percentage of female and their first contact of health care tend to be at medical centers. With the increasing prescriptions of biological agents, the weight of biological agents’ cost to the total drug cost increases significantly (p<0.001). Most patients who were newly prescribed biological agents firstly started with etanercept. Comparing the prescribing patterns at 30 days post-biological agent against the pre-medication period, the consumption of methotrexate, numbers of combined NSAIDs and DMARDs all decreased significantly (p<0.001). However, etanercept new users had more infectious events than control groups.
Seventy-nine adult RA outpatients were successfully interviewed (86% women, mean age 55.23±11.30 years) for assessing QoL. Mean utility value measured by EQ-VAS, EQ-5D index and TTO were 63.66±19.85, 0.71±0.18 and 0.58±0.32, irrespectively. After adjusting demography and EQ-5D dimensions, disease activity is associated with all utility measures, but there are more factors (marriage, selfcare problems, depression and weekly dose of methotrexate) influencing TTO score.
CONCLUSION: Biological agents do reach the short-term clinical effects. However, patients using etanercept acquired higher risk of infectious events. While the long-term safety of newly-lanuched adalimumab remains unclear due to insufficient observation time. Long-term longitudinal follow-up study is necessary to establish the comparative safety of biological agents. For Taiwanese RA patients, EQ-5D index is only and highly associated with the disease activity, and therefore this instrument may be an appropriate to assess local RA patients’ QoL. However, since there is no Taiwanese EQ-5D value sets for deriving EQ-5D index, it is necessary to develop the Taiwanese population-based preference weight for EQ-5D in the future.

並列關鍵字

Rheumatoid arthritis ； biological agents ； outcome ； safety ； quality of life ； Euroqol questionnaire

參考文獻

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