Reduction of Inflammatory and Cardiovascular Proteins in the Blood of Patients with Psoriasis: Differential Responses between Tofacitinib and Etanercept after 4 Weeks of Treatment
Reduction of Inflammatory and Cardiovascular Proteins in the Blood of Patients with Psoriasis: Differential Responses between Tofacitinib and Etanercept after 4 Weeks of Treatment
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DOI：
10.1016/j.jid.2017.08.040
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发表时间：
2018-02-01
影响因子：
6.5
通讯作者：
Krueger, James G.
中科院分区：
文献类型：
--
作者：
Kim, Jaehwan;Tomalin, Lewis;Krueger, James G.
牛皮癣患者心肌梗死的风险增加，牛皮癣现在被认为是冠心病和心血管死亡的独立危险因素。为了了解银屑病药物对与心血管风险相关的全身性炎症的影响，我们研究了托法替尼和依那西普在中度至重度银屑病成人中进行的3期临床试验中与炎症和心血管疾病相关的血液蛋白。在基线和第4周，通过接近延伸法对266例患者的157种血液蛋白进行量化。治疗1个月后，比较托法替尼（10mg，每天2次）和依那西普（50mg，每两周2次）的血液蛋白变化，并观察第12周的反应状态。托法替尼和依那西普通常会降低IL-6、CCL20和CXCL10，但IL-17A仅在两种治疗的应答者中显著降低。与依那西普相比，托法替尼显示出更广泛的心血管血液蛋白还原谱，但托法替尼的蛋白还原作用严格局限于治疗应答者。肿瘤坏死因子受体1、e-选择素、hK11、肿瘤坏死因子相关激活诱导的细胞因子、CHI3L1、IL-16和基质金属蛋白酶-12仅在托法替尼应答者中心血管蛋白显著降低。我们的数据表明，短期系统性银屑病治疗可以减少循环炎症和其他与心血管风险相关的蛋白质。
Patients with psoriasis have an increased risk of myocardial infarction, and psoriasis is now recognized as an independent risk factor for coronary heart disease and cardiovascular mortality. To understand the effects of psoriasis medications on systemic inflammation associated with cardiovascular risks, we studied blood proteins related to inflammation and cardiovascular disease archived from a phase 3 clinical trial of tofacitinib and etanercept in adults with moderate-to-severe psoriasis. A total of 157 blood proteins were quantified by a proximity extension assay from 266 patients at baseline and week 4. Protein changes in the blood after 1 month of treatment were compared between tofacitinib (10 mg two times a day) and etanercept (50 mg biweekly), and by response status at week 12. Tofacitinib and etanercept commonly reduced IL-6, CCL20, and CXCL10, but IL-17A was significantly reduced only in responders of either treatment. Compared with etanercept, tofacitinib showed a wider spectrum of cardiovascular blood protein reduction, but the protein reduction effects of tofacitinib were strictly confined to treatment responders. Tumor necrosis factor receptor 1, E-selectin, hK11, tumor necrosis factorerelated activation-induced cytokine, CHI3L1, IL-16, and matrix metalloproteinase-12 were cardiovascular proteins significantly reduced only in tofacitinib responders. Our data suggest that a short-term systemic psoriasis treatment can cause reductions in circulating inflammatory and other proteins associated with cardiovascular risks.