Progression of joint damage despite control of inflammation in rheumatoid arthritis: a role for cartilage damage driven synovial fibroblast activity.

Rheumatoid arthritis (RA) is a chronic infl ammatory disease that causes progressive joint destruction and consequently functional disability due to the combined effect of chronic synovitis and progressive joint damage. Treatment with disease-modifying drugs and biological agents improves pain, fatigue and disability. More recently, the concept of tight control has been introduced in the treatment of RA. Tight control may be defi ned as a treatment strategy tailored to the disease activity of individual patients, with the aim of achieving a predefi ned level of low disease activity or preferably remission within a reasonable period of time. 1 A goal of remission is reasonably to halt joint damage. However, patients with RA in remission by any established criteria can still experience radiographic progression. 2 In current clinical practice, as well as in most clinical trials, joint destruction is not the explicit target for treatment. Also more recent strict criteria for remission do not take actual joint damage into account and focus on disease activity. 3 In contrast, intensive therapy with antitumour necrosis factor (TNF) alpha plus methotrexate results in no or minimal radiographic progression irrespective of patients' disease activity. 4 This dissociates clinical disease activity from the progression of joint damage. If the prevention of joint damage is a major goal of treatment of RA, monitoring the progression of joint damage more closely is reasonable and needs more attention in future studies. 5 Of course, this should be in addition to controlling disease activity as an expression of, predominantly, joint infl ammation. It can be speculated that disease with dominating joint damage and disease with dominating infl ammation might express the boundaries of different phenotypes of RA. Evidently, (autoimmune) infl ammation as seen in RA constitutes a crucial aspect in disease activity. Investigations concentrate largely on these immune processes. A complex network of immune cells is in charge of an even more complex network of infl ammatory cytokines and chemo-kines that form the root of disease activity. Although less in the spotlight, concurrent with this cytokine activity, a more specia-lised local complex of activities between local synovial cells, particularly fi broblasts, and the neighbouring cartilage and bone tissue, is active at the margins of the joint. As this activity causes actual joint damage , this is also presumed to be a critical process in RA. This local pathology may at least partly be independent of synovial infl ammation as a …