Kahlenberg J Michelle
Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Curr Opin Rheumatol. 2016 May;28(3):197-203. doi: 10.1097/BOR.0000000000000266.
Blockade of interleukin (IL)-1 signaling is one of the oldest biologic therapies, yet the use of these agents is on the rise as the role of IL-1 activation is being recognized in a wide spectrum of inflammatory disorders. This review will cover established and emerging uses of IL-1 antagonism in rheumatic diseases.
Expanding off-label indications for IL-1 blockade include neutrophil-dominant skin diseases, including pyoderma gangrenosum, hidradenitis supperativa, and pustular psoriasis. There is also increasing evidence for the use of IL-1 blockade in heart failure associated with rheumatic diseases. Somatic mosaicism in NLRP3 may explain the onset of later-in-life presentations of periodic fevers which are responsive to IL-1 blockade. Of importance, clinical response to anti-IL-1 therapy does not always denote protection from autoinflammatory disease complications such as macrophage activation syndrome or amyloidosis.
Indications for IL-1 blocking therapies will likely continue to broaden, but given the rarity of many rheumatic diseases which respond to such treatment, rigorous, large clinical trials for each indication are unlikely to occur. Thus, recommended use of these medications will often fall to the discretion of the astute physician. However, medication cost and hurdles of insurance approval, rather than drug efficacy, may be the primary limitation for more widespread use.
白细胞介素(IL)-1信号通路阻断是最古老的生物疗法之一,但随着IL-1激活在广泛的炎症性疾病中的作用得到认可,这些药物的使用正在增加。本综述将涵盖IL-1拮抗在风湿性疾病中的既定和新兴用途。
IL-1阻断的非标签适应症不断扩大,包括以中性粒细胞为主的皮肤病,如坏疽性脓皮病、化脓性汗腺炎和脓疱型银屑病。在与风湿性疾病相关的心力衰竭中使用IL-1阻断的证据也越来越多。NLRP3中的体细胞镶嵌现象可能解释了对IL-1阻断有反应的晚年周期性发热的发病机制。重要的是,对抗IL-1治疗的临床反应并不总是意味着能预防自身炎症性疾病并发症,如巨噬细胞活化综合征或淀粉样变性。
IL-1阻断疗法的适应症可能会继续扩大,但鉴于许多对这种治疗有反应的风湿性疾病较为罕见,针对每种适应症进行严格的大型临床试验不太可能进行。因此,这些药物的推荐使用往往取决于精明医生的判断。然而,药物成本和保险批准的障碍,而非药物疗效,可能是更广泛使用的主要限制因素。