Read Simon J, Dray Andy
AstraZeneca R&D, Office 12AF1A, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK.
Expert Opin Investig Drugs. 2008 May;17(5):619-40. doi: 10.1517/13543784.17.5.619.
Despite exciting progress and growth in the understanding of molecular and cellular mechanisms of chronic pain, osteoarthritis (OA) pain remains a challenging clinical entity to treat. There is an emerging diversity of algogenic mechanisms suggesting heterogeneity in pain aetiology in the OA patient population.
OBJECTIVE/METHODS: This review article summarises key issues in existing therapies for OA pain and highlights the emerging compounds in early and late development. It also highlights where tolerability may be a concern, especially in the older populations in which treatment interactions for co-morbid conditions may further narrow therapeutic index. Importantly, the authors also examine the diversity of biology that underpins OA pain and highlight the opportunities for the future.
RESULTS/CONCLUSIONS: Many emerging therapies are presently in proof-of-concept clinical testing for treatment of OA. A growing understanding of the heterogeneity in the OA patient population, will challenge the ability to accurately understand observed efficacy or safety signals in these relatively small trials and how they may titrate to a broader patient population. We may need to wait several more years to understand whether the need for a differentiated therapy demanded by patients, payors and physicians alike, will be met.
尽管在慢性疼痛的分子和细胞机制理解方面取得了令人兴奋的进展和增长,但骨关节炎(OA)疼痛仍然是一个具有挑战性的临床治疗难题。越来越多的致痛机制表明OA患者群体的疼痛病因存在异质性。
目的/方法:这篇综述文章总结了OA疼痛现有治疗方法中的关键问题,并强调了处于早期和晚期研发阶段的新兴化合物。它还强调了耐受性可能成为问题的方面,特别是在老年人群中,合并症的治疗相互作用可能会进一步缩小治疗指数。重要的是,作者还研究了支撑OA疼痛的生物学多样性,并突出了未来的机遇。
结果/结论:目前许多新兴疗法正处于治疗OA的概念验证临床试验阶段。对OA患者群体异质性的日益了解,将对在这些相对较小的试验中准确理解观察到的疗效或安全信号的能力以及这些信号如何推广到更广泛患者群体提出挑战。我们可能还需要等待数年,才能了解患者、支付方和医生所要求的差异化治疗需求是否能够得到满足。