Giles Jon T, Rist Pamela M, Liao Katherine P, Tawakol Ahmed, Fayad Zahi A, Mani Venkatesh, Paynter Nina P, Ridker Paul M, Glynn Robert J, Lu Fengxin, Broderick Rachel, Murray Meredith, Vanni Kathleen M M, Solomon Daniel H, Bathon Joan M
Columbia University, Vagelos College of Physicians & Surgeons, New York, New York.
Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
ACR Open Rheumatol. 2021 Jun;3(6):371-380. doi: 10.1002/acr2.11256. Epub 2021 May 1.
Individuals with rheumatoid arthritis (RA) are at increased risk for atherosclerotic cardiovascular disease (ASCVD) events relative to the general population, potentially mediated by atherosclerotic plaques that are more inflamed and rupture prone. We sought to address whether RA immunomodulators reduce vascular inflammation, thereby reducing ASCVD risk, and whether such reduction depends on the type of immunomodulator. The TARGET (Treatments Against RA and Effect on 18-Fluorodeoxyglucose [ F-FDG] Positron Emission Tomography [PET]/Computed Tomography [CT]) trial (NCT02374021) will enroll 150 patients with RA with active disease and an inadequate response to methotrexate. Participants will be randomized to add either a tumor necrosis factor (TNF) inhibitor (etanercept or adalimumab) or sulfasalazine and hydroxychloroquine to their background methotrexate. Participants will undergo full-body F-FDG-labelled PET scanning at baseline and after 6 months. Efficacy and safety evaluations will occur every 6 weeks, with therapy modified in a treat-to-target approach. The primary outcome is the comparison of change in arterial inflammation in the wall of the aorta and carotid arteries between the randomized treatment groups, specifically, the change in the mean of the maximum target-to-background ratio of arterial F-FDG uptake in the most diseased segment of either the aorta and carotid arteries. A secondary analysis will compare the effects of achieving low disease activity or remission with those of moderate to high disease activity on vascular inflammation. The TARGET trial will test, for the first time, whether RA treatments reduce arterial inflammation and whether such reduction differs according to treatment strategy with either TNF inhibitors or a combination of nonbiologic disease-modifying antirheumatic drugs.
与普通人群相比，类风湿关节炎（RA）患者发生动脉粥样硬化性心血管疾病（ASCVD）事件的风险增加，这可能是由炎症更严重且更易破裂的动脉粥样硬化斑块介导的。我们试图探讨RA免疫调节剂是否能减轻血管炎症，从而降低ASCVD风险，以及这种降低是否取决于免疫调节剂的类型。“靶向治疗RA及其对18氟脱氧葡萄糖[F-FDG]正电子发射断层扫描[PET]/计算机断层扫描[CT]的影响”（TARGET）试验（NCT02374021）将招募150例患有活动性疾病且对甲氨蝶呤反应不佳的RA患者。参与者将被随机分组，在其基础甲氨蝶呤治疗方案中添加肿瘤坏死因子（TNF）抑制剂（依那西普或阿达木单抗）或柳氮磺胺吡啶和羟氯喹。参与者将在基线时和6个月后接受全身F-FDG标记的PET扫描。每6周进行一次疗效和安全性评估，并采用达标治疗方法调整治疗方案。主要结局是比较随机治疗组之间主动脉壁和颈动脉壁动脉炎症的变化，具体而言，是主动脉和颈动脉最病变节段动脉F-FDG摄取最大靶本底比值的平均值变化。二次分析将比较实现低疾病活动度或缓解与中度至高度疾病活动度对血管炎症的影响。TARGET试验将首次测试RA治疗是否能减轻动脉炎症，以及这种减轻是否因使用TNF抑制剂或非生物改善病情抗风湿药物组合的治疗策略而异。
