细胞因子白细胞介素(IL)-1在免疫介导的疾病中起关键作用,特别是在自身炎症性疾病中。靶向该细胞因子被证明在治疗多种IL-1介导的病变中是有效的。目前,三种IL-1受体阻滞剂被批准,即Anakinra,canakinumab和rilonacept,另外两个有望获得批准,即gevokizumab和bermekimab。然而,目前尚无关于这些生物制剂治疗免疫介导疾病的安全性和有效性的系统评价.
为了评估anakinra的安全性和有效性,canakinumab,rilonacept,gevokizumab,与安慰剂相比,Bermekimab用于治疗免疫介导的疾病,标准护理治疗或其他生物制剂。
PRISMA检查表指导了数据的报告。我们在1984年1月1日至2020年12月31日之间搜索了PubMed数据库,重点是免疫介导的疾病。我们的PubMed文献检索确定了7363篇文章。在筛选纳入和排除标准的标题和摘要并评估全文后,75篇文章被纳入叙事综合。
Anakinra在治疗冷冻比林相关的周期性综合征(CAPS)方面既有效又安全,家族性地中海热(FMF),痛风,巨噬细胞活化综合征,复发性心包炎,类风湿性关节炎(RA),和系统性幼年特发性关节炎(sJIA)。相反,anakinra未能在移植物抗宿主病中显示疗效,干燥综合征,1型糖尿病(T1DM)。Canakinumab显示出治疗CAPS的功效,FMF,痛风,高IgD综合征,RA,Schnitzler综合征,sJIA,和TNF受体相关的周期性综合征。然而,使用canakinumab治疗成人起病的斯蒂尔病和T1DM显示阴性结果。Rilonacept对CAPS的治疗是有效和安全的,FMF,复发性心包炎,和sJIA。相反,在T1DM的治疗中,与安慰剂相比,Rilonacept没有达到优势。Gevokizumab在治疗Behçet疾病相关葡萄膜炎方面显示混合结果,在T1DM中评估时没有获益。Bermekimab在化脓性汗腺炎的治疗中取得了有希望的结果。
这篇针对IL-1靶向生物制剂的系统综述总结了研究的现状,安全,和anakinra的临床疗效,Bermekimab,canakinumab,gevokizumab,和rilonacept治疗免疫介导的疾病。
https://www。crd.约克。AC.英国/PROSPERO/,标识符CRD42021228547。
The cytokine interleukin (IL)-1 plays a pivotal role in immune-mediated disorders, particularly in autoinflammatory diseases. Targeting this cytokine proved to be efficacious in treating numerous IL-1-mediated pathologies. Currently, three IL-1 blockers are approved, namely anakinra, canakinumab and rilonacept, and two additional ones are expected to receive approval, namely gevokizumab and
bermekimab. However, there is no systematic review on the safety and efficacy of these biologics in treating immune-mediated diseases.
To evaluate safety and efficacy of anakinra, canakinumab, rilonacept, gevokizumab, and
bermekimab for the treatment of immune-mediated disorders compared to placebo, standard-of-care treatment or other biologics.
The PRISMA checklist guided the reporting of the data. We searched the PubMed database between 1 January 1984 and 31 December 2020 focusing on immune-mediated disorders. Our PubMed literature search identified 7363 articles. After screening titles and abstracts for the inclusion and exclusion criteria and assessing full texts, 75 articles were included in a narrative synthesis.
Anakinra was both efficacious and safe in treating cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), gout, macrophage activation syndrome, recurrent pericarditis, rheumatoid arthritis (RA), and systemic juvenile idiopathic arthritis (sJIA). Conversely, anakinra failed to show efficacy in graft-versus-host disease, Sjögren\'s syndrome, and type 1 diabetes mellitus (T1DM). Canakinumab showed efficacy in treating CAPS, FMF, gout, hyper-IgD syndrome, RA, Schnitzler\'s syndrome, sJIA, and TNF receptor-associated periodic syndrome. However, use of canakinumab in the treatment of adult-onset Still\'s disease and T1DM revealed negative results. Rilonacept was efficacious and safe for the treatment of CAPS, FMF, recurrent pericarditis, and sJIA. Contrarily, Rilonacept did not reach superiority compared to placebo in the treatment of T1DM. Gevokizumab showed mixed results in treating Behçet\'s disease-associated uveitis and no benefit when assessed in T1DM.
Bermekimab achieved promising results in the treatment of hidradenitis suppurativa.
This systematic review of IL-1-targeting biologics summarizes the current state of research, safety, and clinical efficacy of anakinra,
bermekimab, canakinumab, gevokizumab, and rilonacept in treating immune-mediated disorders.
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021228547.