研究背景
缺血性心臟病是造成類風濕性關節炎患者死亡的主要原因，而在心血管疾病中已知的危險因子之一為糖尿病。類風濕性關節炎患者無論是在糖尿病或是心血管疾病，都有著比一般人還要高的發生率。由過往的研究發現，類風濕性關節炎患者使用hydroxychloroquine (HCQ)可降低糖尿病的發生率，但所觀察的研究族群都為白種人，但西方國家在心血管疾病的發生率和死亡率都與亞洲國家有所差異，因此目前並不知道在亞洲族群身上是否有同樣效果。本研究欲探討臺灣類風濕性關節炎患者使用HCQ與糖尿病發生之風險。

研究方法
本研究為回溯性新使用者世代研究，以全民健康保險研究資料庫作為研究材料，納入在2002年至2008年有連續兩筆(間隔在30天以內)以下四種疾病修飾抗風濕病藥物，methotrexate (MTX)、hydroxychloroquine (HCQ)、leflunomide (LEF)和sulfasalazine (SSZ) 之處方紀錄，且其中任一次就醫紀錄有被診斷類風濕性關節炎者為研究對象。研究終點為患者被診斷為糖尿病並且被處方降血糖藥物(包含胰島素)。本研究之主要分析採用unidirectional 的暴露方式，以時間相依性的Cox比例風險迴歸模型進行分析，探討類風濕性關節炎患者使用HCQ與糖尿病之間的相關性。

研究結果
本研究最終研究對象總人數為26,599人，根據病患用藥暴露情形分成兩組，HCQ使用者為21,969人、未曾使用者為4,630人。本研究發現，在未校正任何因子時，HCQ使用者的糖尿病風險顯著較低於未曾使用者(HR=0.72; 95%信賴區間0.61-0.85, P<.0001)。將所有變項放入校正，HCQ使用者的糖尿病風險依然顯著較低於未曾使用者(HR=0.76; 95%信賴區間0.65-0.90, P=0.0013)。在更進一步進行敏感性試驗及分層分析都得到一致的結果。

研究結論
由本研究結果得知，臺灣類風濕性關節炎患者使用HCQ進行治療，可能可以減少病患後續發生糖尿病的風險。此結果與先前的相關研究一致，但相較於白種人，此預防的效果在亞洲族群的危險性降低幅度較小。

Hydroxychloroquine (HCQ) is one of the disease-modifying antirheumatic drugs (DMARDs) that has been use in the treatment of rheumatoid arthritis (RA) for decades. In addition to the effect of disease controlling, recent studies have discovered that it also reduced the risk of incident DM in RA patients. But the previous study cohort were ethnically homogeneous, mostly Caucasian. Since the difference in cardiovascular diseases (CVDs) profile between Asian and Western population existed, our study sought to evaluate whether this protective effect the same on Asians. Therefore, this study aimed to determine the association between HCQ use and the risk of incident DM in Taiwan RA patients. This study was a retrospective new user cohort study consisted of 26,599 RA patients which were classified as 21,969 HCQ ever users and 4,630 HCQ never users. After adjusting for all covariates, the hazard ratio (HR) for incident DM among HCQ ever users was 0.76 (95% confidence interval (CI), 0.65-0.90; P=0.0013) compared with never users. Our findings supports that HCQ use attenuates the risk of DM in RA patients among Taiwan, which are consistent with previous study. By comparing our results to other previous studies, we suggest that the disease-preventing effect is less in Asians than in Caucasians. Further prospective studies are needed to confirm the protective effect of HCQ in RA patients adjusted with RA disease severity.

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