南臺灣某醫學中心以Imatinib治療慢性骨髓性白血病之臨床果效與生活品質評估之初探

Clinical Effectiveness and Feasibility Study on Quality-of-life Measure for Chronic Myeloid Leukemia Treated with Imatinib at a Medical Center in Southern Taiwan

陳謄州(Teng-Chou Chen)

指導教授 ： 黃耀斌

共同指導教授 ： 張肇松(Chao-Sung Chang)

高雄醫學大學/藥學院/臨床藥學研究所/碩士(2012年)

摘要

背景：蛋白質酪胺酸激酶抑制劑－imatinib的上市，已使慢性骨髓性白血病的病程及存活率顯著改善，卻也使該疾病朝向「慢性化」發展，嚴重衝擊健保藥品花費及醫療預算。然而，在多數資訊來自臨床試驗的狀況下，imatinib目前在台灣有關臨床治療果效及生活品質評估之相關資訊仍缺乏，故無法客觀地評估治療之成本效益。
目的：本研究旨在評估台灣imatinib用於慢性骨髓性白血病之臨床療效及藥物使用模式、回顧目前文獻有關imatinib用於慢性骨髓性白血病之健康相關生活品質測量、並探討台灣慢性骨髓性白血病患者生活品質及健康偏向評估工具在以imatinib治療的慢性骨髓性白血病患者之適用性。
方法：本研究分成三部份：（1）系統性回顧：以結構性搜尋策略檢索實症醫學資料庫，搜尋以imatinib治療後，有關健康狀態及健康偏向之相關測量資訊。（2）病歷回顧：根據臺灣南部某醫學中心之病歷資料，以回溯性世代研究方式，追蹤2000年1月至2011年10月間至以imatinib治療之慢性骨髓性白血病患，自imatinib處方起始日起追蹤至病患死亡或紙本病歷之最後一筆就診記錄為止，收集病患個人基本資料與疾病相關資訊、用藥記錄、檢驗數據、臨床表徵，以評估治療果效及描繪藥物使用路徑。（3）病患訪談：以橫斷性研究方式，針對2011年10月至2012年3月於研究機構門診追蹤，且正以imatinib治療的慢性骨髓性白血病患者，進行一對一半結構式訪談；並以歐洲生活品質量表（EQ-5D index及EQ-VAS）及時間交換法（TTO）調查其生活品質。
結果：（1）系統性文獻回顧：健康狀態測量多收入慢性期的患者。對過去曾接受其他治療或新診斷患者，imatinib能在短時間內顯著改善生活品質。長期用藥患者儘管已產生抗藥性或藥物耐受不佳，其生活品質已接近一般健康大眾；但年輕及女性族群，可能因生理功能或情緒而有較高角色功能限制。就健康偏向測量，不論疾病分期，治療反應皆顯著影響受訪者效用值，但同一個治療狀態的效用值存有顯著性的跨國差異。
（2）病歷回顧：共納入124名個案，平均追蹤時間達3.8年。平均imatinib處方持有率為89.73%，29.41%的個案曾經中斷imatinib使用，且處方持有率顯著地受曾發生grade II血小板低下影響。有67.24%的個案於使用imatinib後第18個月可達完全細胞學緩解，使用imatinib後5年內，整體存活率為75.51%。處方持有率顯著影響個案是否達短期療效指標，且短期療效指標顯著影響死亡與否。
（3）病患訪談：共納入42名受訪者，其平均年齡為50.0±16.0歲，54.5%為男性。EQ-5D index、EQ-VAS及TTO所得之平均效用值各為0.80±0.08、0.78±0.13、0.80±0.18。過去的治療方式及個人病史，與EQ-5D index效用值顯著相關，而EQ-VAS效用值則與性別顯著相關。此外，EQ-5D index及EQ-VAS效用值皆顯著受藥物副作用影響，而查爾森共病症分數則顯著影響TTO效用值。多數患者可接受疾病邁向慢性化且認為目前日常生活功能已無異於一般大眾，服藥方面的困擾多迄因藥物副作用及用藥配合度，家庭經濟因素是長期追蹤的考量。
結論：雖然患者多能達短期療效指標並維持存活，但服藥配合度及中斷用藥確實也成為另一個隱憂。在長期治療果效及成本效益尚待確認的狀況下，有必要針對imatinib用於慢性骨髓性白血病進行進一步成本效益評估。雖然三種測量工具皆適用於以imatinib治療慢性骨髓性白血病之患者，但目前仍無專為使用imatinib治療慢性骨髓性白血病之患者設計的生活品質測量工具，有關使用imatinib之長期追蹤治療果效仍待進一步評估。

關鍵字

慢性骨髓性白血病 ； imatinib ； 臨床果效 ； 生活品質 ； 系統性文獻回顧

並列摘要

Background: Since the launch of Imatinib, the survival and disease progression of chronic myeloid leukemia (CML) has significantly improved, but also resulted in enormous increase in long-term costs. However, neither clinical outcomes nor health-related utility of CML patients has been investigated in Taiwan, and there is a lack of cost-effectiveness evidence to inform the decision-making on long-term resource allocation.
Aim and objectives: This study aimed to explore the medical utilization and clinical outcomes of imatinib treatment for CML, patients' perception of disease and treatments, factors contributing to CML patients' quality of life (QoL), and applicableness of preference-based QoL measurement tools for CML patients treated with imatinib in Taiwan.
Methods: (1) Systematic review: A structured search strategy was used to search evidence-based medicine database for studies reported health status or health preference for CML patient who has ever been treated with imatinib or normal population. (2) Chart review: A cohort study was conducted from January 2000 to October 2011 at a medical center in southern Taiwan. Records were followed from first imatinib prescription to patient died or the last record of chart, or chart review date. CML patients who received imatinib were included to collect patients' basic information, prescribing history, laboratory data, and physical examination to evaluate prescribing pattern and clinical outcome (3) Patient interview: This cross-sectional survey was conducted from October 2011 to March 2012 at oncology outpatient clinics in the study centre. Patients who were diagnosed as CML, treated with imatinib were invited to participate. A semi-structure interview was conducted and the EuroQol group 5-dimension index (EQ-5D index) questionnaire, 100-mm visual analogue scale (EQ-5D VAS), and time-trade off (TTO) was used to evaluate participants' utility.
Results: (1) Systematic review: 6 papers of the health status investigated chronic phase CML patients. Although resistance or intolerance to imatinib during long-term treatment, patients' QoL appeared to be similar to normal population. However, young or female patients had marked limitations in social roles due to physical and emotional problems. Regardless disease stage, utility significantly associated with treatment response. In addition, significant cross country different was found for paitents at the same disease stages.
(2) Chart review: Of all, 124 patients were included and the mean follow-up period is approximately 3.8 year. Mean prescription possession ratios (PPR) were 89.73% and 29.41% for all patients whose imatinib treatment interrupted during follow-up, and PPR was associated with grade II thrombocytopenia. After 18 month of imatinib treatment, 67.24% of the patients achieved complete cytogenetic response. PPR was significantly associated with short-term treatment responses.
(3) Patient interview: Of all, 42 participants (mean age: 50.0±16 years, male: 54.5%) completed the interview survey. Mean utility of EQ-5D index, EQ-5D VAS, and TTO were 0.80±0.08, 0.78±0.13, and 0.80±0.18, respectively. Most patients thought disease become chronic was acceptable, and thought daily living was no longer different from general population. The distress about medication was due to side effect and drug-adhererence. Family economic burden was also a consideration after long-tern care.
Conclusion: Most CML patients treated with imatinib achieved short-term treatment responses, but adherence and treatment interruption were the concerns for long-term outcomes. However, since long-term clinical and cost-effectiveness of imatinib have not yet confirmed, future research on gathering evidence for cost-effectiveness studies are recommanded.

並列關鍵字

chronic myeloid leukemia ； imatinib ； clinical outcome ； quality of life ； systematic review

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