Jain Ankit, Bishnoi Mamta, Prajapati Shiv Kumar, Acharya Sweta, Kapre Sumedha, Singhvi Gautam, Palakurthi Srinath
Industrial Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Pilani Campus, Vidya Vihar, Pilani, 333031, Rajasthan, India.
Department of Pharmaceutical Sciences, Irma Lerma Rangel School of Pharmacy, Texas A&M University, Kingsville, TX, 78363, USA.
J Biol Eng. 2025 Jul 24;19(1):67. doi: 10.1186/s13036-025-00534-8.
To surpass challenges with traditional approaches to treat Rheumatoid arthritis (RA), an improved understanding of molecular-level pathogenesis brought forth targeted therapy with biologics as a great promise in halting the progression of RA. Novel biologics are being designed with the help of synthetic fusion proteins, monoclonal antibodies, and protein fragments, with or without drugs, to target various signaling pathways, including TNF-α, IL-6, JAK, Th-17, IL-family, GM-CSF, B-cell, and T-cell signaling. The journey of biologics in RA management began in 1998 with etanercept (Enbrel). Since then, regulatory bodies have endorsed various biologics and many more are in different clinical stages. This review aims to explore RA by examining current clinical studies with focus on emerging development on molecular-level pathogenesis, prevalent conventional treatment options and their limitations, as well as recent advancements in biologically engineered therapeutics. It also includes a few relevant case studies to support these findings. Despite the progress, challenges remain, such as high costs and the need for safer, more effective delivery methods. The document also touches on the historical perspective of RA, its pathophysiology, and the role of synovial fluid pharmacokinetics in treatment effectiveness. The importance of early diagnosis and well-controlled treatment strategies for RA is paramount. The potential of emerging biological and targeted treatments to facilitate a treat-to-target approach in RA management is substantial. This review explores the key molecular pathways of rheumatoid arthritis and includes detailed figures for better understanding. It also highlights the promising potential of biologically engineered therapeutics, supported by evidence from case studies and clinical trials.
为了克服传统方法治疗类风湿性关节炎（RA）所面临的挑战，对分子水平发病机制的深入理解催生了生物制剂靶向治疗，这为阻止RA进展带来了巨大希望。新型生物制剂借助合成融合蛋白、单克隆抗体和蛋白片段进行设计，有无药物均可，以靶向多种信号通路，包括肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、Janus激酶（JAK）、辅助性T细胞17（Th-17）、白细胞介素家族、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、B细胞和T细胞信号通路。生物制剂在RA治疗中的历程始于1998年的依那西普（恩利）。从那时起，监管机构批准了多种生物制剂，还有更多处于不同临床阶段。本综述旨在通过审视当前临床研究来探索RA，重点关注分子水平发病机制的新进展、常见的传统治疗选择及其局限性，以及生物工程治疗方法的最新进展。它还包括一些相关案例研究来支持这些发现。尽管取得了进展，但挑战依然存在，如成本高昂以及需要更安全、更有效的给药方法。本文还涉及RA的历史背景、病理生理学以及滑液药代动力学在治疗效果中的作用。RA早期诊断和严格控制治疗策略的重要性至关重要。新兴生物和靶向治疗在RA管理中促进达标治疗方法的潜力巨大。本综述探讨了类风湿性关节炎的关键分子途径，并包含详细图表以助于更好理解。它还强调了生物工程治疗方法的巨大潜力，并得到了案例研究和临床试验证据的支持。
