The science of rheumatoid arthritis: a prelude

With respect to research advances, rheumatoid arthritis (RA) has evolved from being largely neglected about a dozen years ago to being one of the most fascinating diseases in medicine. There are a variety of reasons for this metamorphosis, mostly related to renewed interest in studying the many biological facets of the disease, to developments in clinical and basic research, and to stimulation by the results obtained. First, RA develops as a combination of an inflammatory process – synovitis – with a ‘semimalignant’ event, namely the transgression of tissue boundaries characteristic of this erosive disease; although the full details of this transformation remain enigmatic, some important aspects have been elucidated [1,2]. Second, RA involves an autoimmune component, the role of which in the pathogenic cascade is at least a disease-aggravating one [3,4], although this is yet to be sufficiently clarified. Autoimmunity frequently precedes the development of clinical symptoms by many years [5], suggesting an essential or at least closely associated role in pathogenesis, but there is also a slow evolution of the disease through states of ‘pre-arthritis’ and ‘very early arthritis’. Third, novel, validated and reproducible techniques have been developed and used to assess changes in clinical variables and progression of joint destruction [6,7]. Fourth, even though RA is presumably an incurable disorder and traditional disease-modifying antirheumatic drugs, which slow the progression of RA, usually have limited efficacy in established disease [8], these agents appear to be highly effective in very early RA, suggesting that there exists a window of opportunity during which disease can be controlled in many patients [9]. Finally, RA has been a major area for investigations into the efficacy and safety of innovative therapies that target particular cell surface, cell secreted and intracellular molecules [10]. This has not only permitted new treatment options to be realized in clinical practice but it has also yielded insights into the enormously complex pathogenesis of the disease.