摘要：背景和目的：雷诺现象是系统性硬化症的主要表现，提示潜在的血管病变。由于系统性硬化症患者的血管稳定性异常，常有内皮细胞激活，及血循环中内皮素-1水平增高。作为一种4-氨基苯甲酸衍生物，阿米纳酮能降低内皮细胞培养下的内皮素-1产生，本研究旨在评估该药对雷诺现象和继发于系统性硬化症血管病变的作用。

方法：本实验为单中心随机双盲安慰剂对照前瞻性研究。患者服用阿米纳酮75mg，每日3次，治疗12周（整个冬季），或匹配剂量的安慰剂。对比治疗前和治疗12周后的雷诺现象发生次数和严重性，并测定该药对血清内皮素-1水平的影响。

结果：25例患者随机应用阿米纳酮或安慰剂治疗，其中23例（12例阿米纳酮，11例安慰剂）完成实验。两组基线时的临床和人口学特点在统计学上是相配的。结果发现，无药物相关副作用，与安慰剂组相比，阿米纳酮组的雷诺现象次数明显降低(平均: - 67.9% [-40.7%, -83.3%] 对-44.2% [-15.5%,-54.3%]; p=0.06; Mann-Whitney检验)，但雷诺现象严重性得分或持续时间无明显差异，血清内皮素-1水平在治疗组明显降低 (平均 [IQR]: -43.5% [-25.5%, -46.2%]对4.9% [-0.6%, 15.9%]; p=0.02; Mann-Whitney 检验)。

结论：由于样本量较少，故还未达到主要临床终点，阿米纳酮对内皮素-1水平有明显作用。鉴于以前的研究结果（阿米纳酮对长期控制干燥综合征相关的外周血管病变并不劣于波生坦），我们相信随着对该药的进一步研究，可能对系统性硬化症也有长期疗效。

附原文: Description:Background/Purpose: Raynaud’s phenomenon (RP) is a pivotal manifestation of systemic sclerosis (SSc) which reflects an underlying vasculopathy. Endothelial activation with increased circulating levels of Endothelin-1 (ET1) are frequently observed in SSc patients due to a deranged vascular homeostasis. Aminaftone (AMNA) –a derivate of the 4-aminobenzoic acid- was found to be capable of reducing the production of ET-1 in endothelial cell cultures. The present work was conducted to assess the role of AMNA in the treatment of RP and vasculopathy secondary to SSc.Methods: Single-centre, randomized, prospective, double-blinded comparison of AMNA vs placebo. Patients received either 75 mg AMNA 3 times per day for 12 weeks in wintertime, or matching doses of placebo. We compared the number and the severity of RP attacks at baseline and after 12 weeks; furthermore we investigated the effect of AMNA on serum concentrations of ET1.Results: Twenty-five patients were randomized to receive AMNA or placebo; 23 patients (12 AMNA; 11 placebo) did complete the study; no drug-related averse events were observed. The two distinct groups were statistically overlapping for baseline clinical and demographical characteristics. An encouraging and strong trend on the reduction of the number of RP attacks in the AMNA vs placebo group was observed (median: - 67.9% [-40.7%, -83.3%] vs -44.2% [-15.5%,-54.3%]; p=0.06; Mann-Whitney test); no differences in RP severity scores or Rp duration scores were observed. ET-1 serological concentrations were markedly reduced in the treatment arm compared to the placebo arm (median [IQR]: -43.5% [-25.5%, -46.2%] vs 4.9% [-0.6%, 15.9%]; p=0.02; Mann-Whitney test).Conclusion: Although the primary clinical endpoint was not met, most likely due to the low sample size, AMNA was found to have meaningful effects on ET-1 serum levels. In light of the results of a previous report showing the non-inferiority of AMNA compared to bosentan in the long-term control of peripheral SS-related vascular clinical manifestations, when bosentan was not indicated, we believe that further wider and more focused studies (e.g. on the prevention of DU) may be warranted to investigate the long-term effect of AMNA in SSc.

引自: Santaniello, Alessandro MD,Vigone, Barbara MD; Caronni, Monica MD; Beretta, Lorenzo MD.Effect Of Aminaftone On Raynaud's Phenomenon Secondary To Systemic Sclerosis: A Double-Blind Prospective, Randomized, Placebo-Controlled Pilot Study .ACR/ARHP 2013 annual meeting, San Diego, Abstract:#706