Colton Center for Autoimmunity, New York University School of Medicine , New York, NY, USA.
Expert Opin Investig Drugs. 2020 Sep;29(9):1025-1041. doi: 10.1080/13543784.2020.1797677. Epub 2020 Sep 1.
Systemic lupus erythematosus (SLE) is a severe chronic and incurable autoimmune disease. Treatment includes glucocorticoids and immunosuppressants which typically result in partial responses, and hence there is a great need for new therapies. The type I interferon (IFN) pathway is activated in more than 50% of SLE patients, and it is strongly implicated as a pathogenic factor in SLE.
We searched the literature using 'SLE and interferon antagonists' as search terms. This identified a number of therapeutics that have entered clinical development targeting type I IFN in SLE. These include monoclonal antibodies against type I IFN cytokines and a kinoid vaccination strategy to induce anti-IFN antibodies.
Type I IFN antagonists have had some success, but many molecules have not progressed to phase III. These varied results are likely attributed to the multiple concurrent cytokine abnormalities present in SLE, the imprecise nature of the IFN signature as a readout for type I IFN and difficulties with clinical trials such as background medication use and diffuse composite disease activity measures. Despite these challenges, it seems likely that a type I IFN antagonist will come to clinical utility for SLE given the large unmet need and the recent phase III success with anifrolumab.
系统性红斑狼疮（SLE）是一种严重的慢性、无法治愈的自身免疫性疾病。治疗方法包括使用糖皮质激素和免疫抑制剂，这些药物通常只能产生部分缓解效果，因此，非常需要新的治疗方法。超过 50%的 SLE 患者存在 I 型干扰素（IFN）途径的激活，这强烈表明其是 SLE 的致病因素之一。
我们使用“SLE 和干扰素拮抗剂”作为搜索词在文献中进行了搜索。这确定了一些已进入 SLE 中针对 I 型 IFN 的临床开发的治疗方法。这些方法包括针对 I 型 IFN 细胞因子的单克隆抗体和一种 Kinoid 疫苗接种策略，以诱导抗 IFN 抗体。
I 型 IFN 拮抗剂已经取得了一些成功，但许多分子尚未进入 III 期临床试验。这些不同的结果可能归因于 SLE 中存在多种并发的细胞因子异常、IFN 特征作为 I 型 IFN 读出的不精确性以及临床试验中的困难，如背景药物使用和弥漫性复合疾病活动指标。尽管存在这些挑战，但鉴于 SLE 存在巨大的未满足需求以及 anifrolumab 最近在 III 期临床试验中的成功，似乎很有可能会有一种 I 型 IFN 拮抗剂应用于临床。
