Maniscalco Valerio, Abu-Rumeileh Sarah, Mastrolia Maria Vincenza, Marrani Edoardo, Maccora Ilaria, Pagnini Ilaria, Simonini Gabriele
Rheumatology Unit, Meyer Children's University Hospital, Florence, Italy.
Rheumatology Unit, Meyer Children's University Hospital, Viale Gaetano Pieraccini, 24, Firenze, Toscana 50139, Italy.
Ther Adv Musculoskelet Dis. 2020 Oct 16;12:1759720X20959575. doi: 10.1177/1759720X20959575. eCollection 2020.
Interleukin 1 (IL-1), a central mediator of innate immunity, is considered a master cytokine of local and systemic inflammation. IL-1 has emerged as pivotal in the pathogenesis of autoinflammatory diseases (AIDs), and blockade of its pathway has become a crucial target for therapy. Anakinra (ANA), a recombinant IL-1β receptor antagonist, was the first anti-IL-1 agent employed in clinical practice. ANA is currently approved for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, adult-onset Still's disease, and cryopyrin-associated autoinflammatory syndrome. It has also been successfully used for off-label treatment of various monogenic, polygenic, or undefined etiology systemic AIDs. This review describes currently available evidence for the off-label use of ANA in pediatric rheumatologic diseases. Specifically, the use of ANA in Kawasaki disease, idiopathic recurrent pericarditis, Behçet disease, monogenic AIDs, undifferentiated AIDs, chronic non-bacterial osteomyelitis, macrophage activation syndrome, and febrile infection-related epilepsy, in terms of its safety and efficacy. In selected pediatric rheumatic disorders, the off-label administration of ANA appears to be effective and safe. In order to control severe and/or relapsing disease, ANA should be considered as a valuable treatment option in children suffering from rare inflammatory diseases. However, currently available data consist of retrospective studies and short case series; thus, randomized controlled trials and larger series with long-term follow up are mandatory to better assess the efficacy and cost effectiveness of ANA in these challenging patients.
白细胞介素1（IL-1）是固有免疫的核心介质，被认为是局部和全身炎症的主要细胞因子。IL-1已成为自身炎症性疾病（AIDs）发病机制中的关键因素，阻断其信号通路已成为治疗的关键靶点。阿那白滞素（ANA）是一种重组IL-1β受体拮抗剂，是临床实践中使用的首个抗IL-1药物。ANA目前被批准用于治疗类风湿关节炎、全身型幼年特发性关节炎、成人斯蒂尔病和冷吡啉相关的自身炎症综合征。它也已成功用于各种单基因、多基因或病因不明的系统性AIDs的超说明书治疗。本综述描述了目前关于ANA在儿科风湿性疾病中超说明书使用的现有证据。具体而言，探讨了ANA在川崎病、特发性复发性心包炎、白塞病、单基因AIDs、未分化AIDs、慢性非细菌性骨髓炎、巨噬细胞活化综合征和发热感染相关癫痫中的使用情况，包括其安全性和有效性。在某些儿科风湿性疾病中，ANA的超说明书给药似乎是有效且安全的。为了控制严重和/或复发性疾病，对于患有罕见炎症性疾病的儿童，应将ANA视为一种有价值的治疗选择。然而，目前可用的数据包括回顾性研究和简短的病例系列；因此，必须进行随机对照试验和长期随访的更大系列研究，以更好地评估ANA在这些具有挑战性的患者中的疗效和成本效益。
