Pilot studies demonstrate the potential benefits of antiinflammatory therapy in human lymphedema
Pilot studies demonstrate the potential benefits of antiinflammatory therapy in human lymphedema
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DOI：
10.1172/jci.insight.123775
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发表时间：
2018-10-18
期刊：
影响因子：
8
通讯作者：
Nicolls, Mark R.
中科院分区：
文献类型：
--
作者：
Rockson, Stanley G.;Tian, Wen;Nicolls, Mark R.
背景淋巴水肿是一种常见疾病，影响着世界各地数百万人，但仍然缺乏经过批准的药物治疗。由于酮洛芬，非甾体抗炎药，已在实验性水肿的治疗，我们评估其在人类的疗效。我们首先进行了一项探索性开放标签试验。原发性或继发性水肿患者口服酮洛芬75 mg，每日3次，持续4个月。评价受试者的组织病理学变化，皮肤厚度、肢体体积和组织生物阻抗变化作为次要终点。基于我们令人鼓舞的发现，我们接下来进行了一项安慰剂对照试验，主要结果定义为皮肤厚度的变化，通过皮肤卡尺测量。第二项研究的次要终点包括组织病理学、肢体体积、生物阻抗和全身炎症介质。从2010年11月至2011年7月，我们在开放标签试验中招募了21名水肿患者。与基线相比，4个月时组织学和皮肤厚度显著改善。在随访、双盲、安慰剂对照试验中，我们从2011年8月至2015年10月招募了34例患者，其中16例接受酮洛芬治疗，18例接受安慰剂治疗。未发生严重不良事件。酮洛芬接受者的皮肤厚度减少，组织病理学综合指标改善，血浆粒细胞CSF（G-CSF）表达减少。结论。这2项探索性研究共同支持酮洛芬靶向治疗水肿患者的效用。我们的研究结果强调了这种方法有助于恢复失败的淋巴循环的前景。
BACKGROUND. Lymphedema is a common condition affecting millions around the world that still lacks approved medical therapy. Because ketoprofen, an NSAID, has been therapeutic in experimental lymphedema, we evaluated its efficacy in humans.METHODS. We first performed an exploratory open-label trial. Patients with either primary or secondary lymphedema received ketoprofen 75 mg by mouth 3 times daily for 4 months. Subjects were evaluated for changes in histopathology, with skin thickness, limb volume, and tissue bioimpedance changes serving as secondary endpoints. Based on our encouraging findings, we next conducted a placebo-controlled trial, with the primary outcome defined as a change in skin thickness, as measured by skin calipers. Secondary endpoints for this second study included histopathology, limb volume, bioimpedance, and systemic inflammatory mediators.RESULTS. We enrolled 21 lymphedema patients in the open-label trial, from November 2010 to July 2011. Histopathology and skin thickness were significantly improved at 4 months compared with baseline. In the follow-up, double-blind, placebo-controlled trial, we enrolled 34 patients from August 2011 to October 2015, with 16 ketoprofen recipients and 18 placebo-treated subjects. No serious adverse events occurred. The ketoprofen recipients demonstrated reduced skin thickness, as well as improved composite measures of histopathology and decreased plasma granulocyte CSF (G-CSF) expression.CONCLUSION. These 2 exploratory studies together support the utility of targeted antiinflammatory therapy with ketoprofen in patients with lymphedema. Our results highlight the promise of such approaches to help restore a failing lymphatic circulation.