The CCP Study: Coordinated Programme to Prevent Arthritis - Can We Identify Arthritis at a Pre-clinical Stage ?

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There is accumulating evidence for the need to identify patients with rheumatoid arthritis (RA) early. Damage occurs early and early treatment is effective. Clearly there is a need to improve ways of identifying these patients. It is recognised that patients with RA often have non-specific musculosk...

There is accumulating evidence for the need to identify patients with rheumatoid arthritis (RA) early. Damage occurs early and early treatment is effective. Clearly there is a need to improve ways of identifying these patients. It is recognised that patients with RA often have non-specific musculoskeletal complaints in the months or years prior to development of RA (unpublished observations). Family members of patients with RA are also at greater risk of developing RA. Given we know that earlier identification of patients enables earlier treatment and this leads to better long-term outcomes, we need a method of identifying patients at the pre-clinical stage of disease. C-reactive protein (CRP) is an acute phase reactant, produced by the liver, primarily in response to stimulation by interleukin-6 (IL-6). The lower limit of detection of routine CRP is 8mg/dL (or higher), yet the mean CRP in the general population is <2mg/dL11 (as measured by high sensitivity assays). Therefore, patients with early RA may have low-grade inflammation not detected by routine CRP. This has been demonstrated in patients with established disease12, but no studies have been done in early disease. Disease activity variables correlated with increases in highly-sensitive CRP (hs-CRP) and hs-CRP was better than ESR at predicting disease activity and severity12. Interestingly, on retrospective analysis of blood donor serum, increased levels of hs-CRP have been noted in RA patients during the pre-clinical phase, most commonly within the two years prior to symptom onset13. This suggests immunologic changes occur prior to the development of the symptomatic stage and provides an exciting tool for assisting in the diagnosis of very early inflammatory disease

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