Department of Immunology, University Hospital Zurich, Zurich, Switzerland.
Faculty of Medicine, University of Zurich, Zurich, Switzerland.
Front Immunol. 2022 Jul 6;13:888392. doi: 10.3389/fimmu.2022.888392. eCollection 2022.
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.
细胞因子白细胞介素 (IL)-1 在免疫介导的疾病中发挥关键作用，尤其是在自身炎症性疾病中。靶向这种细胞因子已被证明在治疗许多由 IL-1 介导的疾病方面是有效的。目前，已有三种 IL-1 阻滞剂（阿那白滞素、卡那单抗和利那鲁单抗）获得批准，另外两种（gevokizumab 和 bermekimab）预计也将获得批准。然而，目前尚无关于这些生物制剂在治疗免疫介导性疾病方面的安全性和疗效的系统评价。
评估阿那白滞素、卡那单抗、利那鲁单抗、gevokizumab 和 bermekimab 与安慰剂、标准治疗或其他生物制剂相比，在治疗免疫介导性疾病方面的安全性和疗效。
PRISMA 清单指导数据报告。我们在 1984 年 1 月 1 日至 2020 年 12 月 31 日期间在 PubMed 数据库中搜索免疫介导性疾病的信息。我们的 PubMed 文献检索共确定了 7363 篇文章。在筛选标题和摘要以确定纳入和排除标准，并评估全文后，有 75 篇文章被纳入叙述性综合分析。
阿那白滞素在治疗 Cryopyrin 相关周期性综合征 (CAPS)、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、类风湿关节炎 (RA) 和全身幼年特发性关节炎 (sJIA)方面既有效又安全。然而，阿那白滞素在移植物抗宿主病、干燥综合征和 1 型糖尿病 (T1DM)方面没有显示出疗效。卡那单抗在治疗 CAPS、FMF、痛风、高 IgD 综合征、RA、Schnitzler 综合征、sJIA 和 TNF 受体相关周期性综合征方面显示出疗效。然而，卡那单抗在治疗成人Still 病和 T1DM 方面的应用结果为阴性。利那鲁单抗在治疗 CAPS、FMF、复发性心包炎和 sJIA 方面既有效又安全。相反，与安慰剂相比，利那鲁单抗在治疗 T1DM 方面并未显示出优越性。Gevokizumab 在治疗 Behçet 病相关葡萄膜炎方面显示出混合结果，在评估 T1DM 时则没有获益。Bermekimab 在治疗化脓性汗腺炎方面取得了良好的效果。
本系统评价对白细胞介素 1 靶向生物制剂进行了总结，概述了阿那白滞素、bermekimab、卡那单抗、gevokizumab 和利那鲁单抗在治疗免疫介导性疾病方面的当前研究状况、安全性和临床疗效。
https://www.crd.york.ac.uk/PROSPERO/，标识符 CRD42021228547。
