Yu Shirley Pei-Chun, Hunter David John
a 1 Royal North Shore Hospital, Department of Rheumatology , St. Leonards, NSW 2065, Sydney, Australia.
Expert Opin Emerg Drugs. 2015 Sep;20(3):361-78. doi: 10.1517/14728214.2015.1037275. Epub 2015 Jul 3.
Osteoarthritis (OA) is the most prevailing form of joint disease, with symptoms affecting 10 - 12% of the adult population with a projection of a 50% increase in prevalence in the next two decades. The disease characteristics are defined by articular cartilage damage, low-grade synovial inflammation and hypertrophic bone changes, leading to pain and functional deterioration. To date, available pain treatments are limited in their efficacy and have associated toxicities. No structural disease modification agents have been approved by regulatory agencies for this indication.
We reviewed drugs in Phase II - III for OA pain and joint structure modification. Different aspects of structure modification are divided into targets of inflammatory pathway, cartilage catabolism and anabolism, and subchondral bone remodeling.
Further insight into the pathophysiology of the disease will allow for development of novel target classes focusing on the link between symptomatology and structural changes. Given the complexity of OA, one single therapy is unlikely to be universally and uniformly effective. Promising therapies are under development, but there are obstacles in the translation of treatment from preclinical models and trial designs need to be cognizant of the complex reasons for previous trial failures.
骨关节炎(OA)是最常见的关节疾病形式,症状影响10% - 12%的成年人口,预计在未来二十年患病率将增加50%。该疾病的特征表现为关节软骨损伤、低度滑膜炎症和骨质增生变化,导致疼痛和功能恶化。迄今为止,现有的疼痛治疗方法疗效有限且伴有毒性。尚无结构疾病修饰药物获监管机构批准用于此适应症。
我们综述了处于II - III期用于OA疼痛和关节结构改善的药物。结构改善的不同方面分为炎症途径靶点、软骨分解代谢和合成代谢靶点以及软骨下骨重塑靶点。
对该疾病病理生理学的进一步深入了解将有助于开发针对症状与结构变化之间联系的新型靶点类别。鉴于OA的复杂性,单一疗法不太可能普遍且一致有效。有前景的疗法正在研发中,但从临床前模型转化至治疗存在障碍,试验设计需要认识到既往试验失败的复杂原因。