Rheumatoid arthritis is one of the most important chronic inflammatory conditions in the United Kingdom, causing significant morbidity and mortality in individuals who are given the diagnosis. (1,2) RA also carries a considerable financial burden, costing the NHS £560 million annually and an estimated £3.8 - £4.8 billion a year to the UK economy as a whole. Diagnosis and treatment strategies have progressed and transformed in recent years, particularly with the introduction of biologic agents. Approximately 4500 patients are commenced on biologic therapy per year, at an annual cost of £160 million to the NHS. Despite this, a substantial number of patients (approximately 30-40%) remain “resistant” to treatment.(2,3)

Current NICE Guidance and the need for Stratification: the role of B-cells within the synovium

Current NICE guidelines recommend that patients who fail to respond to anti-TNF agents should be commenced on Rituximab, a monoclonal antibody against CD20 antigen expressed by B-cells. Other biologic agents include Tocilizumab, an inhibitor of interleukin 6(IL-6) which mediates inflammation within the joint. Current data suggests that the response to Rituximab therapy is variable, with only 60% reaching an ACR20 response at 6 months. (4)

We are a strong musculoskeletal unit and through our pathobiology of early arthritis (PEAC) cohort have pioneered minimally invasive ultrasound guided synovial biopsies in the UK. The use of this diagnostic tool will allow us to stratify responders / non-responders to Rituximab according to their synovial pathotype; more specifically to the absence or presence of B-cells within the joint lining. We have excellent links with other centres and will collaborate with the Barts Cancer Institute and Genome Centre at the William Harvey Research Institute in order to gain sight into disease response and relapse at the molecular and genomic level.

Our overall goals are to provide better clinical care through timely, stratified intervention with an appropriate choice of biologic, thus improving efficacy and reducing cost to the NHS.

Understanding the molecular basis of response and relapse will allow us to further understand the inflammatory process and ultimately open pathways into further therapies that will achieve and sustain disease remission.

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  1. Silman AJ. Epidemiology of rheumatoid arthritis. Apmis 1994;102:721-8.
  2. Scott DL, Symmons DP, Coulton BL, Popert AJ. ‘Long-term outcome of treating rheumatoid arthritis: results after 20 years’ Lancet 1987;1:1108-11.
  3. Breedveld FC, Weisman MH, Kavanaugh AF, et al. ‘The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment.’ Arthritis and rheumatism 2006;54:26-37.
  4. Kristensen LE, Kapetanovic MC, Gulfe A, Soderlin M, Saxne T, Geborek P. Predictors of response to anti-TNF therapy according to ACR and EULAR criteria in patients with established RA: results from the South Swedish Arthritis Treatment Group Register. Rheumatology (Oxford, England) 2008;47:495-9

The R4-RA trial is funded by the MRC-NIHR Efficacy and
Mechanism Evaluation Programme