Innovaderm Research, Inc, Montreal, Quebec, Canada.
J Am Acad Dermatol. 2010 Mar;62(3):427-36. doi: 10.1016/j.jaad.2009.05.042.
Interferon-alfa (IFN-alpha) has been implicated in the pathogenesis of psoriasis.
To evaluate the safety profile of MEDI-545, a fully human anti-IFN-alpha monoclonal antibody and to explore its effect on the involvement of type I IFN-alpha activity in the maintenance of established plaque psoriasis.
We conducted an 18-week, randomized, double-blind, placebo-controlled, dose-escalating study in 36 subjects with chronic plaque psoriasis. Subjects received one intravenous dose of MEDI-545 (0.3-30.0 mg/kg) or placebo. Study outcomes were safety profile, pharmacokinetics, immunogenicity, and clinical effects.
There was no difference in adverse events between MEDI-545 and placebo. Two serious adverse events were reported; one drug-related hypotensive infusion reaction occurred in one subject in the 30.0 mg/kg MEDI-545 dose group, causing discontinuation of study drug in that subject and study dismissal of the other subjects in the same cohort; and a myocardial infarction occurred in one subject in the 10 mg/kg MEDI-545 dose group, which was considered to be unrelated to treatment. MEDI-545 was nonimmunogenic, had a half-life of 21 days, showed no significant inhibition of the type I IFN gene signature, and had no clinical activity.
The study addressed only IFN-alpha and chronic psoriatic lesions.
The safety profile of MEDI-545 supports further clinical development. IFN-alpha does not appear to be significantly involved in the maintenance of established plaque psoriasis.
干扰素-α（IFN-α）被认为与银屑病的发病机制有关。
评估完全人源抗 IFN-α单克隆抗体 MEDI-545 的安全性，并探讨其对 I 型 IFN-α活性在维持已建立的斑块状银屑病中的作用。
我们进行了一项为期 18 周、随机、双盲、安慰剂对照、剂量递增的研究，纳入了 36 例慢性斑块状银屑病患者。患者接受 MEDI-545（0.3-30.0mg/kg）或安慰剂单次静脉注射。研究终点为安全性、药代动力学、免疫原性和临床疗效。
MEDI-545 与安慰剂组的不良事件无差异。报告了 2 例严重不良事件；1 例发生在 30.0mg/kg MEDI-545 剂量组的药物相关低血压输注反应，导致该患者停止研究药物，同一队列的其他患者退出研究；1 例 10mg/kg MEDI-545 剂量组发生心肌梗死，认为与治疗无关。MEDI-545 无免疫原性，半衰期为 21 天，对 I 型 IFN 基因特征无明显抑制作用，无临床疗效。
该研究仅涉及 IFN-α和慢性银屑病病变。
MEDI-545 的安全性支持进一步的临床开发。IFN-α似乎并未显著参与已建立的斑块状银屑病的维持。
