Qualification of ultrasonography as a biomarker of prognosis and response to therapy in rheumatoid arthritis

风湿性关节炎是一种渐进性致残性疾病，影响约1%的人口。虽然新的生物疗法对大约三分之一的患者无效，但治疗方面已经取得了相当大的进展。此外，诸如抗TNF的生物治疗通过注射施用并且非常昂贵，使得在英国存在配给。只有那些患有最活跃疾病的患者才有资格参加，尽管这种治疗在预防进行性关节损伤方面特别有效。开发生物标志物的需求尚未得到满足，该生物标志物将允许医生准确地预测哪些患者可能具有快速和进行性的关节破坏，使得这些患者可以用可用的最有效的预防性治疗来治疗，而不必等到他们已经患病一段时间，到该阶段损伤已经完成并且在很大程度上不可逆。首先，我们想研究一种简单的、非侵入性的超声技术，它可以提供有关血流的信息，作为识别预后不良患者的预测工具。第二，由于并非所有患者都对现有疗法有反应，而且昂贵的疗法并不像理想的那样广泛可用，因此需要新的、负担得起的药物。然而，药物开发过程本身是非常昂贵的，并且在没有对大量患者进行测试的情况下，证明药物干预后疾病的任何改善都是由于药物本身。因此，我们试图研究血流超声测量的潜力，以在较少的患者中提供对新治疗反应的敏感、早期和可靠的指示。如果这种方法是成功的，研究结果将有更广泛的影响，更具有成本效益的方法，以新的药物测试在未来（a）使新的药物发现类风湿性关节炎更有效，（B）尽量减少患者暴露于药物已被证明没有显着的好处。

Rheumatoid arthritis is a progressively disabling disease affecting about 1% of the population. There have been considerable advances in treatment, although the new biologic therapies are not effective in about one-third of patients. Furthermore, biologic treatments such as anti-TNF are administered by injection and are very costly, such that there is rationing in the UK. Only those patients with the most active disease become eligible, despite the particular effectiveness of this type of treatment in preventing progressive joint damage. There is an unmet need to develop biomarkers that will allow a doctor to accurately predict which patients are likely to have rapid and progressive joint destruction, so that these patients can be treated with the most effective preventative treatments available without having to wait until they have had disease for some time, by which stage the damage is already done and largely irreversible. Firstly, we want to look at a simple, non-invasive ultrasound technique that gives information about blood flow as such a predictive tool to identify poor prognosis patients. Secondly, because not all patients respond to the available therapies and the expensive ones are not as widely available as would be ideal, there is a need for new, affordable drugs. However, the drug development process itself is very costly and it is not always straightforward to prove that any improvements in disease after drug intervention are due to the drug itself without testing it on very large numbers of patients. Therefore, we seek to investigate the potential of ultrasound measures of blood flow to give a sensitive, early, and reliable indication of response to new treatments in smaller numbers of patients. If this approach is successful, the findings will have wider implications for more cost-effective approaches to new drug testing in future to (a) make new drug discovery for rheumatoid arthritis more efficient, and (b) minimize patient exposure to drugs that have turned out to have no significant benefit.