Roman-Blas Jorge A, Bizzi Emanuele, Largo Raquel, Migliore Alberto, Herrero-Beaumont Gabriel
a Bone and Joint Research Unit, Service of Rheumatology, IIS-Fundación Jiménez Díaz , Autonomous University of Madrid , Madrid , Spain.
b UOS of Rheumatology , S. Pietro Fatebenefratelli Hospital , Rome , Italy.
Expert Opin Pharmacother. 2016 Sep;17(13):1745-56. doi: 10.1080/14656566.2016.1201070. Epub 2016 Jul 4.
The lack of a complete understanding of the complex processes involved in the etiopathogenesis and subsequent appropriate phenotyping makes it difficult to find therapies that may be efficacious in most patients with osteoarthritis (OA). Consensus recommendations involve mainly non-pharmacological approaches. Analgesics and NSAIDs are considered second choice options due to their poor efficacy/safety ratios. To some extent, OA may be considered an orphan disease. Therefore, there is an urgent need to identify effective and safe new pharmacologic modalities for treating OA.
This review is based on a Medline comprehensive literature search for published articles evaluating new formulations of current drugs and promising emerging therapies in OA. We discuss the current status of novel systemic agents in development including potent analgesic options, inhibitors of innate immunity, inducible nitric oxide synthase (iNOS), pro-inflammatory cytokines and cartilage proteases as well as bone agents. Furthermore, we also revise the potential benefit of intraarticular (IA) therapy with hyaluronic acid (HA), pro-inflammatory mediator blockers, cartilage anabolic agents, mesenchymal stem cell and gene transfer.
Despite the renewed interest in the search of new compounds for treatment of OA, results have been limited. Novel systemic and IA administered agents are in active development. IA drug administration is particularly an attractive approach because can diminish some of the severe side effects associated with systemic drugs. Indeed, one of the most promising fields for pharmacology innovation in OA is joint injected therapy, as suggested by preliminary data from recent studies using IA sprifermin (rhFGF-18), mesenchymal stem cells or TGF-B1 transduced allogenic chondrocytes. Last, the effort to develop new drugs must be accompanied by the interest for establishing well-defined phenotypes, and only then, a more tailored therapy should be practiced in OA.
由于对骨关节炎（OA）发病机制中涉及的复杂过程缺乏全面了解，以及后续未能进行适当的表型分析，使得难以找到对大多数OA患者有效的治疗方法。共识性建议主要涉及非药物治疗方法。由于镇痛剂和非甾体抗炎药（NSAIDs）的疗效/安全性较差，它们被视为第二选择。在某种程度上，OA可被视为一种罕见病。因此，迫切需要确定治疗OA的有效且安全的新药物治疗方式。
本综述基于对Medline数据库的全面文献检索，以查找评估OA中现有药物新剂型和有前景的新兴疗法的已发表文章。我们讨论了正在研发的新型全身用药的现状，包括强效镇痛选择、先天免疫抑制剂、诱导型一氧化氮合酶（iNOS）、促炎细胞因子和软骨蛋白酶抑制剂以及骨药物。此外，我们还回顾了透明质酸（HA）、促炎介质阻滞剂、软骨合成代谢剂、间充质干细胞和基因转移的关节内（IA）治疗的潜在益处。
尽管对寻找治疗OA的新化合物重新产生了兴趣，但结果有限。新型全身用药和关节内用药正在积极研发中。关节内给药尤其具有吸引力，因为它可以减少与全身用药相关的一些严重副作用。事实上，正如最近使用关节内注射司普明（rhFGF - 18）、间充质干细胞或转化生长因子 - β1（TGF - β1）的同种异体软骨细胞的研究所提供的初步数据所示，关节内注射治疗是OA药物创新最有前景的领域之一。最后，开发新药的努力必须伴随着对建立明确表型的关注，只有这样，才能在OA中实施更具针对性的治疗。
