Mirsaeidi Mehdi, Kaplan Jeffrey, Affeldt John, Berkovich Regina, Askanase Anca
College of Medicine-Jacksonville, University of Florida, 15255 Max Leggett Parkway, Jacksonville, FL, 32218, USA.
Kansas City Multiple Sclerosis & Headache Center, Overland Park, KS, USA.
Adv Ther. 2025 Sep 15. doi: 10.1007/s12325-025-03359-5.
Corticosteroids have long been a standard-of-care treatment for chronic immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. However, corticosteroids are associated with potentially serious adverse effects and may be ineffective in cases of resistant or refractory disease. Acthar Gel, a naturally sourced complex mixture of porcine pituitary peptides, is a noncorticosteroid alternative that is approved by the US Food and Drug Administration to treat a variety of IMIDs and autoimmune conditions. These include infantile spasms, systemic lupus erythematosus, exacerbations of multiple sclerosis and rheumatoid arthritis, and several ocular inflammatory disorders. Preclinical and clinical studies have shown that the immunomodulatory effects of Acthar Gel are distinct from those of corticosteroids and other adrenocorticotropic hormone (ACTH)-class therapeutics. For example, Acthar Gel stimulates both steroid-dependent and steroid-independent pathways that may mitigate inflammation. In this narrative review, we summarize the immunomodulatory effects of Acthar Gel, with a focus on its potential mechanisms in immune cells, such as B cells, T cells, and macrophages. These effects are thought to be mediated by binding and activation of transmembrane melanocortin receptors expressed on these immune cells. Receptor binding initiates an intracellular signal transduction cascade that ultimately regulates the expression of anti-inflammatory genes. Collectively, the experimental and clinical studies reviewed here suggest that Acthar Gel acts as an immunomodulator via melanocortin receptors and may be an effective anti-inflammatory therapeutic option for patients with IMIDs who are refractory or intolerant to corticosteroids.Graphical Abstract available for this article.
长期以来，皮质类固醇一直是类风湿关节炎、系统性红斑狼疮和多发性硬化症等慢性免疫介导性炎症疾病（IMIDs）的标准治疗方法。然而，皮质类固醇会带来潜在的严重不良反应，并且在耐药或难治性疾病中可能无效。Acthar Gel是一种天然来源的猪垂体肽复合混合物，是一种非皮质类固醇替代药物，已获美国食品药品监督管理局批准用于治疗多种IMIDs和自身免疫性疾病。这些疾病包括婴儿痉挛症、系统性红斑狼疮、多发性硬化症和类风湿关节炎的病情加重，以及几种眼部炎症性疾病。临床前和临床研究表明，Acthar Gel的免疫调节作用与皮质类固醇和其他促肾上腺皮质激素（ACTH）类疗法不同。例如，Acthar Gel刺激类固醇依赖性和非类固醇依赖性途径，可能减轻炎症。在这篇叙述性综述中，我们总结了Acthar Gel的免疫调节作用，重点关注其在免疫细胞（如B细胞、T细胞和巨噬细胞）中的潜在机制。这些作用被认为是通过与这些免疫细胞上表达的跨膜黑皮质素受体结合并激活来介导的。受体结合启动细胞内信号转导级联反应，最终调节抗炎基因的表达。总体而言，本文综述的实验和临床研究表明，Acthar Gel通过黑皮质素受体发挥免疫调节作用，对于对皮质类固醇难治或不耐受的IMIDs患者可能是一种有效的抗炎治疗选择。本文提供图形摘要。
