Hermann Walter, Lambova Sevdalina, Muller-Ladner Ulf
Department of Rheumatology and Clinical Immunology, Justus-Liebig-University Giessen, Kerckhoff-Klinik GmbH, Giessen, Germany.
Department of Propaedeutics of Internal Diseases, Faculty of Medicine, Medical University - Plovdiv, Plovdiv, Bulgaria.
Curr Rheumatol Rev. 2018;14(2):108-116. doi: 10.2174/1573397113666170829155149.
Osteoarthritis (OA) is the most common joint disease and a leading cause for impaired function and disability with significant treatment costs and socio-economic burden. Despite recent achievements in the knowledge on disease pathogenesis, the treatment is still a challenge and contrary to the inflammatory joint diseases, no disease-modifying drugs are currently available for OA. Different response in different localizations of the disease further complicates the therapeutic choice. The standard pharmacological treatment includes agents for control of pain and inflammation (non-steroidal anti-inflammatory drugs, analgesics including opioids, intraarticular corticosteroids) and the group of the symptomatic slow acting drugs for OA such as glucosamine sulfate, chondroitin sulfate, diacerein, unsaponifiables extract of soybean and avocado administered orally and intrarticular hyaluronic acid. In addition, a number of studies investigate the efficacy of classic disease-modifying drugs used in inflammatory arthritides and antiresoptive agents as potential future therapies that could prevent structural progression of the disease. In a number of small studies, therapeutic efficacy of hydroxychloroquine (HCT) in OA has been suggested, but the results are contradictory. The first results from a multicenter, randomized, double-blind, placebo-controlled trial focused on symptomatic hand OA were recently reported (British HERO study). It has been concluded that HCQ was not superior than placebo as analgesic treatment or for reduction of the radiographic progression in hand OA. Placebo-controlled trial evaluating the efficacy of HCT in inflammatory and erosive hand OA is under way (OA TREAT study). Another field of recent research is the efficacy of TNF-alpha blockers based on the knowledge of their high efficacy in the inflammatory joint diseases and the significant role of TNF-alpha in the pathogenesis of OA. However, current evidence from the available studies does not support the use of TNF-alpha blockers in OA. The benefit of TNF-alpha blockers in specific sub-groups of patients with higher level of inflammation, objective criteria for the expected responders as well as cost-effectiveness of such treatment is a matter of further research and discussion. New biologic agents that target the nerve growth factor-β are other currently investigated drugs as a potential symptomatic therapeutic option in OA. Significant research has been also focused on revealing potential symptomatic or eventually disease-modifying efficacy of drugs that target bone metabolism due to contemporary notion for the crucial role of the subchondral bone in OA pathology and the positive association between the increased subchondral bone turnover and the progressive cartilage loss. A significant delay of joint width narrowing vs. placebo has been observed in patients with symptomatic knee OA after treatment with strontium renelate. The intraarticular administration of platelet-rich plasma is evaluated as potential future therapy and has been tried in knee and hip OA with beneficial effect. Based on the current knowledge about the OA pathogenesis and the undergoing studies, new therapies for OA are awaited both as a safe symptomatic treatment - alternative to the conventional treatment options and as a disease-modifying therapy that would revolutionize the contemporary approach to OA.
骨关节炎(OA)是最常见的关节疾病,是导致功能受损和残疾的主要原因,治疗成本高昂且社会经济负担沉重。尽管在疾病发病机制的认识方面取得了最新进展,但治疗仍然是一项挑战,与炎症性关节疾病不同,目前尚无用于OA的改善病情药物。疾病在不同部位的不同反应进一步使治疗选择复杂化。标准的药物治疗包括控制疼痛和炎症的药物(非甾体抗炎药、包括阿片类药物在内的镇痛药、关节内注射皮质类固醇)以及OA的症状性慢作用药物组,如硫酸氨基葡萄糖、硫酸软骨素、双醋瑞因、大豆和鳄梨的不皂化物提取物,口服和关节内注射透明质酸。此外,一些研究调查了用于炎症性关节炎的经典改善病情药物和抗吸收剂作为未来潜在疗法预防疾病结构进展的疗效。在一些小型研究中,已表明羟氯喹(HCT)对OA有治疗效果,但结果相互矛盾。最近报道了一项针对症状性手部OA的多中心、随机、双盲、安慰剂对照试验的初步结果(英国HERO研究)。得出的结论是,在手部OA的镇痛治疗或减少影像学进展方面,HCQ并不优于安慰剂。评估HCT对炎症性和侵蚀性手部OA疗效的安慰剂对照试验正在进行中(OA TREAT研究)。近期研究的另一个领域是基于TNF-α阻滞剂在炎症性关节疾病中的高效性以及TNF-α在OA发病机制中的重要作用,研究其疗效。然而,现有研究的当前证据不支持在OA中使用TNF-α阻滞剂。TNF-α阻滞剂在炎症水平较高的特定患者亚组中的益处、预期反应者的客观标准以及这种治疗的成本效益是进一步研究和讨论的问题。靶向神经生长因子-β的新型生物制剂是目前作为OA潜在症状性治疗选择进行研究的其他药物。由于目前认为软骨下骨在OA病理中起关键作用,且软骨下骨转换增加与软骨渐进性丢失呈正相关,因此大量研究也集中在揭示靶向骨代谢的药物的潜在症状性或最终改善病情的疗效上。雷奈酸锶治疗后,症状性膝关节OA患者的关节宽度变窄与安慰剂相比有显著延迟。富血小板血浆的关节内注射作为未来潜在疗法正在评估中,并已在膝关节和髋关节OA中试用,取得了有益效果。基于目前对OA发病机制的认识和正在进行的研究,既期待有新的疗法作为安全的症状性治疗——替代传统治疗选择,也期待有改善病情的疗法能彻底改变当代OA的治疗方法。