布鲁顿酪氨酸激酶(BTK)抑制剂是多发性硬化症(MS)的新兴治疗药物。BTK在B细胞和骨髓细胞中表达,其中的关键祖细胞包括树突状细胞,小胶质细胞和巨噬细胞,MS发病机制的整体效应,连同肥大细胞,建立BTK抑制剂与多种自身免疫性疾病的相关性。第一代BTK抑制剂目前用于治疗B细胞恶性肿瘤,并在B细胞调节中显示出功效。B细胞消耗疗法已显示出成功的MS疾病改善治疗(DMT),强调BTK抑制剂对这一适应症的潜力;然而,第一代BTK抑制剂具有挑战性的安全性,不适合长期使用,根据MSDMT的要求。第二代高选择性BTK抑制剂已在临床前和临床研究中显示出调节MS相关发病机制的功效。这些BTK抑制剂中的六种正在进行MS的临床开发,其中三个也在调查慢性自发性荨麻疹(CSU),类风湿性关节炎(RA)和系统性红斑狼疮(SLE)。选定BTK抑制剂治疗MS的II期试验显示,磁共振成像扫描显示新的钆增强病变减少;然而,长期使用的安全性尚未确定.通过结合正在进行的第二代BTK抑制剂治疗MS的II期和III期试验的安全性见解,对安全性的理解正在发展。CSU,RA和SLE。这篇叙述性综述调查了BTK抑制剂作为MSDMT的潜力,第二代抑制剂的选择性提高,迄今为止,通过临床开发计划建立了比较安全性见解,并提出了对女性生殖健康和长期管理的影响。
布鲁顿酪氨酸激酶抑制剂在多发性硬化症中的应用综述为什么要进行这项研究?这项研究是为了了解目前对一种药物的了解,称为布鲁顿酪氨酸激酶抑制剂,或BTK抑制剂。目前正在研究六种BTK抑制剂作为治疗多发性硬化症(MS)的可能新药。这六种药物中的一些也正在被研究作为治疗慢性自发性荨麻疹的可能的新药,类风湿性关节炎和系统性红斑狼疮。这些都是自身免疫性疾病,免疫系统错误地攻击身体部位。临床科学家想了解目前对BTK抑制剂的了解,它们在实验室中的工作方式以及治疗自身免疫性疾病的安全性。这可以帮助我们更多地了解MS中的BTK抑制剂。科学家们做了什么?科学家们评估了这六种BTK抑制剂的现有研究,通过一个被称为文献综述的过程。这些是正在进行的临床试验的结果,以及通过在实验室研究BTK抑制剂收集的信息。研究人员拼凑了所有这些发现,来制作这篇总结结果的论文。科学家们发现了什么?科学家们发现,大多数BTK抑制剂对MS的研究仍在进行中。到目前为止,BTK抑制剂在大多数研究中似乎显示出合理的安全性,但现在知道还为时过早。研究人员还发现了BTK抑制剂在实验室中的工作原理,关于如果长期服用药物会发生什么,以及它们如何影响女性生殖健康。这些发现意味着什么?这些发现将帮助其他科学家更多地了解MS中的BTK抑制剂。BTK抑制剂用于MS的试验仍在进行中,但是拼凑所有当前的发现可以提供我们所知道的以及仍然需要做的事情。
Bruton\'s tyrosine kinase (BTK) inhibitors are an emerging class of therapeutics in multiple sclerosis (MS). BTK is expressed in B-cells and myeloid cells, key progenitors of which include dendritic cells, microglia and macrophages, integral effectors of MS pathogenesis, along with mast cells, establishing the relevance of BTK inhibitors to diverse autoimmune conditions. First-generation BTK inhibitors are currently utilized in the treatment of B-cell malignancies and show efficacy in B-cell modulation. B-cell depleting therapies have shown success as disease-modifying treatments (DMTs) in MS, highlighting the potential of BTK inhibitors for this indication; however, first-generation BTK inhibitors exhibit a challenging safety profile that is unsuitable for chronic use, as required for MS DMTs. A second generation of highly selective BTK inhibitors has shown efficacy in modulating MS-relevant mechanisms of pathogenesis in preclinical as well as clinical studies. Six of these BTK inhibitors are undergoing clinical development for MS, three of which are also under investigation for chronic spontaneous urticaria (CSU), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Phase II trials of selected BTK inhibitors for MS showed reductions in new gadolinium-enhancing lesions on magnetic resonance imaging scans; however, the safety profile is yet to be ascertained in chronic use. Understanding of the safety profile is developing by combining safety insights from the ongoing phase II and III trials of second-generation BTK inhibitors for MS, CSU, RA and SLE. This narrative review investigates the potential of BTK inhibitors as an MS DMT, the improved selectivity of second-generation inhibitors, comparative safety insights established thus far through clinical development programmes and proposed implications in female reproductive health and in long-term administration.
A review of Bruton’s tyrosine kinase inhibitors in multiple sclerosis Why was this study done? This study was done to find out about current knowledge on a type of drug, called Bruton’s tyrosine kinase inhibitors, or BTK inhibitors. There are currently six BTK inhibitors being studied as a possible new drug for treating multiple sclerosis (MS). Some of these six drugs are also being studied as a possible new drug for chronic spontaneous urticaria, rheumatoid arthritis and systemic lupus erythematosus. These are all autoimmune conditions, where the immune system mistakenly attacks parts of the body. Clinician scientists wanted to understand what is currently known about BTK inhibitors, how they work in the laboratory and how safe they could be for treating autoimmune conditions. This could help us understand more about BTK inhibitors in MS.What did the scientists do? The scientists assessed existing research on these six BTK inhibitors, through a process known as a literature review. These were results from ongoing clinical trials, and information collected through studying BTK inhibitors in laboratories. The researchers pieced together all these findings, to produce this paper that summarizes the results.What did the scientists find? The scientists found that most studies of BTK inhibitors for MS are still ongoing. So far, BTK inhibitors seem to show reasonable safety in most studies, but it is too early to know. The researchers also found out about how BTK inhibitors work in the lab, about what could happen if the drugs are taken for a long time and how they could impact female reproductive health.What do these findings mean? These findings will help other scientists learn more about BTK inhibitors in MS. Trials with BTK inhibitors for MS are still ongoing, but piecing together all the current findings gives a picture of what we know and what still needs to be done.