IL-1, as a target for dry eye disorder: Anakinra (Kineret)

Rec IL-Ra proved to be effective against dry eye syndrome 22-Apr-2013 The clinical trial results published in JAMA Ophthalmology reported that anti-arthritic drug, recombinant version of human IL-Ra was found to be effective against dry eye syndrome. The topical drug formulation Anakinra (Kineret) is being manufactured by Amgen Inc., Researchers from the Harvard Medical School, Brigham and Women's Hospital, Massachusetts Eye and Ear studied the efficacy of the anti-arthritic therapy against dry eye disorder, and the team believe the protein drug could be a targeted molecular treatment. According to Dr. Reza Dana, the team assessed the therapeutic effects of IL-1Ra over a decade and the team achieved a significant research milestone. The trial results proved the commitment of the team and also the potency of targeted therapy against other eye ailments, he added.  Dry eye disorder is linked with over-expression of inflammatory cytokines such as Interleukin 1 (IL-1) and the therapeutic benefits of the existing therapies are limited due to adverse events. Drugs such as topical corticosteroids, tetracycline derivatives and cyclosporine A are being used in such treatment. IL-1Ra, originally approved for the treatment of arthritis treatment antagonizes IL-1 mediated inflammation by binding with interleukin receptors (IL-1a and IL-1 receptor 1). Pre-clinical studies confirmed the efficacy of the recombinant protein drug against dry eye disorder, ocular inflammation, corneal transplant rejection and allergic conjunctivitis. A randomized, double-blinded clinical trial has been conducted to assess the safety and efficacy of topical IL-R1A in dry eye disorder patients. 75 participants were included in the trial and were studied over 16 weeks. The participants randomly received either 2.5% Anakinra or 5% of Anakinra or an eye lubricant in 2:1:2. The patients reported that Anakinra was more effective and safe than the eye lubricant in improvement of dry eye disorder symptoms. 2.5% of Anakinra was four times more effective than other two drug formulations, and it alleviated corneal staining. Discontinuation of Anakinra but not the lubricant application at week 12 worsened the symptoms between 12 and 16 weeks. It is a clear evidential support about the potential therapeutic effect of Anakinra. The trial results are encouraging, and no previous clinical trials reported such results in dry eye disease treatment. IL-1Ra is safe, well-tolerated ophthalmic drop that can treat the underlying cause of the treatment. The positive results were confirmed by rapid relief of symptoms, and the patients were able to return to routine daily activities very soon, she added.

风湿性关节炎药物或可用于治疗干眼病 发布时间：2013-4-24 来源：药品资讯网信息中心 干眼（DED）是引发个体眼部不适、视觉障碍以及引发眼表炎症的一种常见病症，在美国大约有900万人遭受这种疾病的影响，其中有很多人当其暴露于低湿度环境或者使用隐形眼镜时就会引发眼部的轻度不适。近日，来自哈佛大学医学院等处的研究者通过研究揭示，一种用于治疗人类风湿性关节炎的IL1受体抑制剂-阿那白滞素（anakinra，IL-1Ra）可以明显降低干眼病的症状，阿那白滞素的局部应用在治疗干眼病上是一项空前的突破，相关研究成果刊登于国际杂志JAMA OPHthalmology上。研究者Reza Dana博士表示，我们实验室在10年前就开始寻找阿那白滞素在治疗途径上的可能性，如今这项临床试验非常可喜，研究结果不仅为我们治疗数百万干眼病患者提供了希望，而且有利于研究者开发其它的眼部疾病的疗法。 前期研究揭示了，DED和炎性细胞因子的过度表达明显相关，包括眼镜中的白细胞介素1，然而目前针对DED炎性成分的治疗途径非常有限，而且有些有效的方法还会产生副作用。抗炎药物如四环素衍生物等可以有效用于治疗DED，其可以下调白细胞介素1的产量，并且上调白细胞介素1受体拮抗剂的产量。 这项研究中，研究者开展了一项随机双盲的临床试验用于评估干眼病患者局部IL-1Ra使用的安全性，研究者对75个参与者进行了长达16周的以2：2：1的比例进行随机的分配实验接受眼部润滑剂，其中2.5%或者5%的患者接受阿那白滞素。研究发现，病人对阿那白滞素耐受，而且阿那白滞素的效果比眼部润滑剂的效果好很多。而且局部阿那白滞素的使用可以明显降低干眼病的症状，效果是使用眼部润滑剂的6倍。研究者最后表示，我们此前绝对不会想到阿那白滞素在治疗干眼病上的明显作用，我们还会继续努力去研究发现一种更为安全、耐受性的眼药水来治疗干眼病，而不是仅仅掩盖住干眼病的不良症状。