台灣類風濕性關節炎患者罹患惡性腫瘤的相關因子

Abstract

研究背景：類風濕性關節炎是一種慢性、全身性、發炎性自體免疫疾病，已知癌症的發生與發炎有相關，且過去研究亦顯示類風濕性關節炎患者罹患癌症的風險較一般人稍高，但是目前對於類風濕性關節炎患者罹患這些癌症的風險增加原因並不清楚。 研究目的：本研究目的為分析台灣類風濕性關節炎病人使用疾病修飾藥物治療對罹患惡性腫瘤風險的相關性。 研究方法：本研究以國家衛生研究院全民健康保險學術資料庫2005年百萬承保歸人檔為資料來源，選出2003到2010年間有就醫資料者，針對20歲以上領有重大傷病卡的類風濕性關節炎的病人，排除過去有癌症病史、資料不全的就診資料，共有1,756人納入研究分析。其中有服用細胞毒殺性疾病修飾抗風濕藥物及抗腫瘤壞死因子藥物病人數為352人，而沒有服用的病人數有1,404人，再利用Propensity Score Matching 方法進行樣本配對，共有692人納入研究分析，其中有無服用細胞毒殺性疾病修飾抗風濕藥物及抗腫瘤壞死因子藥物病人數各為346人。統計方法包括威爾克森符號等級檢定、卡方檢定、Cox Proportional Hazard Regression及Multiple regression analysis。 研究結果：類風濕性關節炎病人罹患癌症的盛行率為3.99%，其中服用細胞毒殺性疾病修飾抗風濕藥物及抗腫瘤壞死因子藥物病人罹患癌症的盛行率為3.17%，而沒有服用的病人罹患癌症的盛行率為4.00%。服用細胞毒殺性疾病修飾抗風濕藥物及抗腫瘤壞死因子藥物病人的平均罹癌時間為986 天，而沒有服用者為1161天（p<0.6673）。經多變項分析結果顯示罹病三年以下的病人罹患癌症的風險（Hazard Ratio）較高且達統計上顯著差異。 研究結論：本研究結果顯示台灣類風濕性關節炎病人服用細胞毒殺性疾病修飾抗風濕藥物及抗腫瘤壞死因子藥物病人並未呈現顯著增加罹患癌症的風險；另外罹患類風濕性關節炎時間較短的病人發生癌症的風險較高，可能的解釋為過去臨床上對罹患類風濕性關節炎初期治療並未採取較積極的治療策略，因此病人的發炎狀態可能普遍為高，因而造成癌症的發生風險增加。但是由於本研究係採用百萬承保歸人檔做為研究資料來源，在研究盛行率不高的疾病及事件上容易低估結果，使得因果關係的相關強度不高，因此本研究之結果發現在未來仍需分析更完整的資料庫來做確認。

Background：Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disease; inflammation has been linked to malignancy. Moreover, RA patient have been shown higher risk of malignancy compare with general population in the previous studies. However, the reasons of increase risk of malignancy in RA patient remains unknown. Objective：This study aimed to analyze the risk of malignancy Taiwanese RA patients in receiving disease-modifying therapy. Method：This study was based on data from the Longitudinal Health Insurance Database (LHID) 2005 released by the National Health Research Institute, contains data on all medical benefit claims from 1997 through 2010 for a subset of 1 million beneficiaries randomly sampled from the 2005 enrollment file. Patients with RA catastrophic illness certificate between Jan 1st, 2003 to Dec 31st, 2010 and age ≥20years old were included, totally1, 756 RA patients were identified. Among them, receiving cytotoxic-DMARDs and anti-TNF treatment were 352 patients while no receiving above treatment were 1,404 patients. Further, we used propensity score matching to balance covariates between two groups, finally 692 RA patients were matched, 346 patients in each group. Wilcoxon signed Rank test, Chi-square Test, Cox Proportional Hazard Regression Model and Multiple regression analysis were applied to test the risk of malignancy in receiving different disease-modifying therapy. Result：The prevalence of malignancy among Taiwanese RA patients was 3.99%, the prevalence of malignancy in receiving cytotoxic-DMARDs and anti-TNF treatment was 3.17 while no receiving above treatment was 4.00%. In addition, the average time from RA diagnosed to malignancy diagnosed in receiving cytotoxic-DMARDs and anti-TNF treatment was 986 days while no receiving above treatment was 1,161 days (p<0.6673). By multivariate analysis, the risk of malignancy was higher in RA disease duration less than 3 years patients. Conclusion：This study did not find significantly increased malignancy risk of Taiwanese RA Patient in receiving cytotoxic-DMARDs and anti-TNF treatment. Besides, less RA duration patients have higher risk of malignancy might be due to conservative treatment strategy and causes higher inflammation exist in the early stage of RA, this might led to higher risk of malignancy in less disease duration patients. However, because the 2005 LHID of one million insured people was utilized for this study, the strength of causality might be more likely to be influenced when analyzing low prevalence diseases and rare events. Therefore, more complete database analyses are required in the future to confirm the results of this study.