Pathobiology of Early Arthritis Cohort (PEAC)

Rheumatoid arthritis (RA) is a diverse disease with some patients suffering from a mild disease while others develop a more aggressive course. At present it is impossible to predict from the outset the final disease outcome. Expert opinion favours the use of aggressive treatment in all patients with early RA including the use of the new biological agents (magic bullets). Given the high costs of these drugs (#10,000/year/patient) and their potential toxicity it is imperative to tailor early treatment to patients most at risk of poor outcome.

In some other inflammatory conditions such as kidney diseases specific treatments are guided by the severity of the tissue pathology determined following examination of the tissue under the microscope. We propose to validate and use the same concept to treat patients with RA. Patients would have a small piece of tissue (synovial biopsy) taken from the joint at disease outset that will be analysed for specific features that might give clues on the severity of the disease enabling doctors to target specific therapies to those most in need.

This together with studying biological markers in the blood and urine of these patients will enable scientist to investigate potential causes regarding the origin, evolution and treatment of arthritis.

It is hoped that the elucidation of key pathways involved in the perpetuation or resolution of inflammation will lead to the development of new drugs (and/or the testing currently available drugs in a better way) that will facilitate induction of remission in the majority of patients. This in turn will result in less joint damage and consequent disability with considerable alleviation of suffering for patients and their family as well as reduction of the health-economic burden on the NHS and society in general.

Rheumatoid arthritis (RA) is one of the most important chronic inflammatory disorders in the UK. It affects approximately 1% of adults, causes considerable morbidity, reduces quality of life, increases mortality and results in large medical costs (over #1.2 billion/year). Importantly, RA behaves clinically as a heterogeneous condition with a variable clinical course and major differences in joint damage scores and consequent disability. Thus, it is crucial to tailor potentially toxic and expensive drugs (biologic #10k/year/patient/) to the individual patient?s needs as well as for targeting limited health care resources. Current prognostic algorithms are insufficiently sensitive at presentation to reliably identify individuals that will progress to destructive arthritis and hence functional and economic decline.

The purpose of the application is to address this unmet clinical need by developing a prospective cohort of early inflammatory arthritis patients with the goal of creating a unique resource with high-density data including genotyping, biologic tissue characterisation, state?of-the-art 3/4D ultrasound-US/power-Doppler-PDU imaging, and detailed clinical phenotyping that will enable us to search for early predictors of disease evolution as well as to examine the role of multiple cellular and molecular pathways involved in joint destruction and therapeutic response.

Thus, this cohort will represent an ideal platform for innovative clinical trials with stratified entry according to imaging, biologic and clinical profile that will be of major interest to academia, industry and government bodies. In particular, it is envisaged that time integrated US/PDU imaging will improve on currently employed composite clinical assessment tools permitting earlier evaluation of response to therapy and development of novel prognostic algorithms of structural damage progression. Equally, the comprehensive collection of samples (particularly synovial tissue through a US guided minimally invasive biopsy) will facilitate research in the fields of Genomics, Transcriptomics, Proteomics, Metabonomics, Cell and Humoral Biology enabling scientists to test and generate hypotheses on the disease origin, susceptibility and diverse outcome.

Despite being a common disease there have been few cohorts in the UK that have systematically collected clinical, radiological, genetic and biological data. The Pathobiology of Early Arthritis Cohort (PEAC) will provide such a unified approach. It will lead to a step change in the way in which clinical, imaging and immune-pathologic data is collated and integrated in the UK, allowing UK rheumatologists to have a unique resource to compete within the EU arena, where complementary but distinct approaches in the Netherlands and Scandinavia have proven to be highly informative and successful.