Genzyme Corporation-Orthopaedics, Framingham, MA 01701, USA.
Expert Opin Emerg Drugs. 2011 Sep;16(3):479-91. doi: 10.1517/14728214.2011.576670. Epub 2011 May 4.
Osteoarthritis (OA), the most prevalent form of joint disease, affects as much as 13% of the world's population. In the USA, it is the leading cause of disability in people over age 65 and is characterized by progressive cartilage loss, bone remodeling, osteophyte formation and synovial inflammation with resultant joint pain and disability. There are no treatments marketed for structural disease modification; current treatments mainly target symptoms, with > 75% of patients reporting need for additional symptomatic treatment.
Drugs in later development (Phase II - III) for OA pain and joint structural degeneration are reviewed. Topics that are not covered in this article are procedural-based (e.g., arthrocentesis, physical therapy), behavioral-based (e.g., weight loss, pain coping techniques) or device-based (e.g., knee braces, surgical implants) treatments.
More in-depth understanding of the pathophysiology of the disease, as well as elucidation of the link between clinical symptomatology and structural changes in the joint will likely lead to the development of novel target classes with promising efficacy in the future. Efficacy notwithstanding, there remain significant hurdles to overcome in clinical development of these therapeutics, inherent in the progression pattern of the disease as well as challenges with readouts for both pain and structure modification trials.
骨关节炎(OA)是最常见的关节疾病,影响全球多达 13%的人口。在美国,它是 65 岁以上人群残疾的主要原因,其特征是渐进性软骨丧失、骨重塑、骨赘形成和滑膜炎症,导致关节疼痛和残疾。目前没有针对结构疾病修正的治疗方法上市;目前的治疗方法主要针对症状,超过 75%的患者报告需要额外的对症治疗。
本文综述了处于后期开发(II 期-III 期)阶段的用于 OA 疼痛和关节结构退化的药物。本文未涉及的主题包括基于程序的(例如关节穿刺术、物理疗法)、基于行为的(例如减肥、疼痛应对技术)或基于器械的(例如膝关节支具、手术植入物)治疗方法。
对疾病病理生理学的更深入理解,以及阐明临床症状与关节结构变化之间的联系,可能会导致未来开发出具有潜在疗效的新型靶向药物类别。尽管疗效显著,但这些治疗方法在临床开发中仍存在重大障碍,这是疾病进展模式以及疼痛和结构修正试验的检测指标所带来的挑战。