Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Maryland School of Medicine , Baltimore, MD, USA.
Division of Gerontology, Department of Epidemiology and Public Health, University of Maryland School of Medicine , Baltimore, USA.
Expert Opin Investig Drugs. 2020 Dec;29(12):1339-1346. doi: 10.1080/13543784.2020.1842357. Epub 2020 Nov 8.
: Osteoarthritis (OA) is the most common form of arthritis. Knee OA is associated with joint pain, activity limitation, physical disability, reduced health-related quality of life, and increased mortality. To date, all pharmacologic treatments for OA are directed toward pain management. Lorecivivint (LOR) is an investigational agent that has potential as a disease-modifying osteoarthritis drug (DMOAD). It modulates the Wnt signaling pathway by inhibiting CDC-like kinase 2 and dual-specificity tyrosine phosphorylation-regulated kinase 1 A which are molecular regulators in Wnt signaling, chondrogenesis, and inflammation. : This paper discusses the current pharmacologic guidelines for the treatment of knee OA and illuminates the potential of a new agent, Lorecivivint, as a disease-modifying osteoarthritis drug (DMOAD). Efficacy and safety and the challenges for this novel agent come under the spotlight. : LOR may be a potential DMOAD for the treatment of patients with knee OA. While the Phase 2A trial did not meet its primary endpoint, preplanned analyses did identify a target population for further evaluation of its potential as a DMOAD. Phase 3 trials are ongoing, but this intra-articular drug is currently considered safe and well tolerated, with no significant reported systemic side effects.
骨关节炎(OA)是最常见的关节炎类型。膝骨关节炎与关节疼痛、活动受限、身体残疾、降低健康相关生活质量和增加死亡率有关。迄今为止,所有治疗 OA 的药物都针对疼痛管理。Lorecivivint(LOR)是一种具有成为治疗骨关节炎的药物(DMOAD)潜力的研究性药物。它通过抑制 CDC 样激酶 2 和双特异性酪氨酸磷酸化调节激酶 1A 来调节 Wnt 信号通路,这两种分子调节剂在 Wnt 信号转导、软骨生成和炎症中发挥作用。本文讨论了治疗膝骨关节炎的当前药物治疗指南,并阐明了新型药物 Lorecivivint 作为治疗骨关节炎的药物(DMOAD)的潜力。该新型药物的疗效和安全性以及面临的挑战成为关注的焦点。LOR 可能是治疗膝骨关节炎患者的一种有潜力的 DMOAD。虽然 2A 期试验未达到其主要终点,但预先计划的分析确实确定了一个目标人群,以进一步评估其作为 DMOAD 的潜力。3 期试验正在进行中,但这种关节内药物目前被认为是安全且耐受良好的,没有报告明显的全身副作用。