Arthritis in space and time--to boldly go!

Despite the profound impact of biologics on the treatment of rheumatoid arthritis (RA), long lasting disease remission remains elusive. We propose that this is a consequence of failing to target the right molecular pathway in the most relevant patient group at the appropriate time and place in disease progression. A limitation to testing this approach is the availability of disease models representing the discrete steps in autoimmune pathogenesis. A particular example is the paucity of models to dissect the conditions permissive for the breach of self-tolerance, which would subsequently allow identification and testing of therapeutics for re-establishment of self-tolerance. We conclude that a detailed understanding of the location and timing of events leading to the systemic breach of self-tolerance and subsequent progression to tissue specific pathology are required if rational application of existing drugs and identification of novel targets is to be achieved. This will take the personalised medicine revolution into the realms of contextualised medicine, whereby the right drug is targeted to the right tissue, in the right patient, at the right time.