Assessing the Safety of Biologic Disease Modifying Anti-Rheumatic Drugs in Pa

类风湿性关节炎患者服用生物修饰抗风湿药物的安全性评价 类风湿性关节炎(RA)患者的预期寿命比一般人短 他们患严重感染、早期心血管疾病、胰岛素的风险增加 耐药和淋巴增生性肿瘤。目前类风湿性关节炎的治疗是以抗风湿治疗为主。 药物(DMARDS)，包括新的肿瘤坏死因子α(TNFa)生物拮抗剂和 白介素1(IL-1)。这些药物通过阻断关键的炎症介质，控制RA的活性； 然而，这些相同的机制也会削弱免疫反应，使患者更容易 易感染病原体或细胞异常增殖的。是否使用生物DMARDS进行治疗 增加类风湿关节炎患者严重感染和肿瘤的风险仍然存在争议。 肿瘤坏死因子α拮抗剂已被评估用于治疗非心力衰竭患者。 风湿病。没有显示出任何益处，矛盾的是，高剂量的DMARD 对某些病人来说是有害的。然而，生物性DMARDS对RA患者的心脏影响 如果没有先前存在的充血性心力衰竭，目前尚不清楚。 RA增加了冠心病的风险，这是传统风险无法完全解释的 各种因素。慢性炎症被认为在这种加速的发病机制中起着不可或缺的作用。 动脉硬化。尽管先前的研究表明DMARD疗法可以降低 心血管疾病在RA中，特异性DMARDS对心肌梗死风险的影响尚不清楚。 慢性炎症也与代谢综合征和胰岛素抵抗有关，众所周知 动脉粥样硬化的危险因素和类风湿关节炎患者的高度流行状况。糖皮质激素 治疗矛盾地改善了类风湿关节炎患者的胰岛素敏感性，这表明炎症和 胰岛素抵抗可能与此密切相关。此外，IL-1受体拮抗剂Anakinra的效果也有所改善 糖尿病患者的血糖控制和英夫利昔单抗改善了RA患者的胰岛素抵抗。 无论这种益处是否延伸到其他DMARD，或者DMARD治疗是否可以推迟糖尿病的发病 在类风湿关节炎患者中的作用目前尚不清楚。 为了评估生物DMARDS在RA患者中的安全性，我们提出了一系列研究 有三个具体目标：1)检验使用生物DMARDS增加严重急性呼吸综合征风险的假设 感染与传统的DMARDS相比。2)检验使用生物DMARDS的假设 与传统的DMARDS相比，增加了发生淋巴增生性肿瘤的风险。3)至 检验使用生物DMARDS会增加充血性心力衰竭风险并降低 与传统的DMARDS相比，心肌梗死和糖尿病的风险更低。

Assessing the Safety of Biologic Disease Modifying Anti-Rheumatic Drugs in Patients with Rheumatoid Arthritis Patients with rheumatoid arthritis (RA) have shorter life expectancy compared to the general population and they are at increased risk for serious infections, early cardiovascular disease, insulin resistance and lymphoproliferative neoplasias. Current treatment of RA is based on disease modifying antirheumatic drugs (DMARDs), including novel biologic antagonists of tumor necrosis factor alpha (TNFa) and interleukin 1 (IL-1). Through the blockade of key inflammatory mediators, these drugs control RA activity; however, these same mechanisms could also impair immune responses, rendering patients more susceptible to infectious agents or abnormal cell proliferation. Whether or not therapy with biologic DMARDs increases the risk of serious infections and neoplasias among patients with RA remains controversial. TNFa antagonists have been evaluated for the treatment of congestive heart failure in patients without rheumatic diseases. No benefits were shown and paradoxically, high doses of these DMARDs were deleterious in some patients. Nevertheless, the cardiac effects of biologic DMARDs in patients with RA but without preexisting congestive heart failure remain unclear. RA imparts an increased risk for coronary heart disease that is not fully explained by traditional risk factors. Chronic inflammation is postulated to play an integral role in the pathogenesis of this accelerated atherosclerosis. Although previous studies suggested that DMARD therapy could reduce the risk of cardiovascular disease in RA, the effect of specific DMARDs on the risk of myocardial infarction is unknown. Chronic inflammation is also associated with the metabolic syndrome and insulin resistance, known risk factors for atherosclerosis and highly prevalent conditions among patients with RA. Glucocorticoid therapy paradoxically improved insulin sensitivity in patients with RA, suggesting that inflammation and insulin resistance may be closely related. Furthermore, anakinra, the IL-1 receptor antagonist, improved glucose control in patients with diabetes, and infliximab improved insulin resistance in patients with RA. Whether this benefit extends to other DMARDs or whether DMARD therapy can delay the onset of diabetes in patients with RA is currently unknown. To evaluate the safety of biologic DMARDs in patients with RA, we propose a sequence of studies with three specific aims: 1) To test the hypothesis that use of biologic DMARDs increases the risk of serious infections compared with traditional DMARDs. 2) To test the hypothesis that use of biologic DMARDs increases the risk of developing lymphoproliferative neoplasias compared with traditional DMARDs. 3) To test the hypothesis that use of biologic DMARDs increases the risk of congestive heart failure and decreases the risk of myocardial infarction and diabetes compared with traditional DMARDs.