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

类风湿性关节炎是一种渐进性致残性疾病，影响约1%的人口。尽管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步。此外，抗肿瘤坏死因子等生物治疗是通过注射进行的，而且非常昂贵，因此在英国实行配给。尽管这种治疗在防止进行性关节损伤方面特别有效，但只有那些疾病最活跃的患者才符合条件。有一种尚未得到满足的需求，即开发生物标记物，使医生能够准确预测哪些患者可能出现快速和渐进性的关节破坏，以便这些患者可以使用可用的最有效的预防性治疗，而不必等到他们患病一段时间后，损害已经造成，基本上是不可逆转的。首先，我们想看看一种简单的、非侵入性的超声技术，它可以提供血流信息，作为一种预测工具来识别预后不良的患者。其次，由于并非所有患者都对可用的疗法有反应，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，而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，并不总是直接的。因此，我们试图研究超声血流测量的潜力，以便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。如果这种方法成功，这些发现将对未来更具成本效益的新药测试方法产生更广泛的影响，以(A)使治疗类风湿性关节炎的新药发现更有效，以及(B)将患者对事实证明没有显著好处的药物的接触降至最低。

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.