Background


 

Rheumatoid arthritis 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 and increases mortality and results in large medical costs (over £1.2 billion/year) (1).

Rheumatoid arthritis - Hands
Rheumatoid arthritis - Bones

As severe RA leads to structural damage within two years of onset, if effective disease control is not achieved (2), early aggressive treatment is recommended (3, 4). Treatment protocols are guided by some well-established prognostic algorithms (5) that include clinical parameters and positive autoantibodies such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP). However, particularly at presentation when patients with synovitis might fall into different diagnostic (RA vs non-RA including undifferentiated poly arthritis UPA) as well as disease severity categories, these markers are insufficiently sensitive to reliably identify individuals that will progress to destructive arthritis and hence functional and economic decline (6, 7).

Rheumatoid arthritis - Knee
Rheumatoid arthritis - Synovitis

Despite being a common disease there have been few cohorts in the UK that have systematically collected clinical, radiological, genetic and biological data. 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.

Of critical relevance, even when the 'diagnosis' is established by virtue of composite diagnostic criteria, RA behaves clinically as a heterogeneous condition with a variable clinical course and major differences in joint damage scores: 10-12 fold after 10 years of disease (8). Thus, it is critical to tailor treatment on an individual patient basis according to prognosis-severity categories. Therefore, it remains of critical importance to develop better prognostic/predictive (bio)-markers of joint erosion at presentation not only to determine the most effective allocation of expensive biologic disease modifying therapies but, above all, to prevent disability and the consequent considerable costs for individuals and society.

The development of a prospective early arthritis cohort with high quality clinical and imaging data (state-of-the-art 3D/4D ultrasound-US / power-Doppler-PDU imaging) together with a comprehensive collection of biological samples (blood, urine and synovial tissue) will provide a unique resource to search for early predictors of disease evolution as well as to enable early proof of concept/mechanistic studies with stratified entry according to the imaging and immunological profile. Thus, this cohort will represent an ideal platform for clinical trials of novel substances. 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 prognostic algorithms of structural damage progression. Equally, the comprehensive collection of samples (particularly synovial tissue through a US guided minimally invasive biopsy) will enable scientists to test and generate hypotheses on the disease origin, natural course and response to treatment.

References

  1. N. J. Cooper, Rheumatology. (Oxford) 39, 28 (2000).
  2. T. Mottonen et al., Arthritis Rheum. 46, 894 (2002).
  3. J. M. Albers et al., Ann. Rheum. Dis. 60, 453 (2001).
  4. P. Emery, BMJ 332, 152 (2006).
  5. H. Visser, C. S. le, K. Vos, F. C. Breedveld, J. M. Hazes, Arthritis Rheum. 46, 357 (2002).
  6. A. L. Jansen et al., J. Rheumatol. 29, 2074 (2002).
  7. K. Raza et al., J. Rheumatol. 32, 231 (2005).
  8. F. Wolfe, S. H. Zwillich, Arthritis Rheum. 41, 1072 (1998).
 

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