RHEUMATOID ARTHRITIS
Rheumatoid arthritis (RA) is an extremely painful, debilitating, and destructive inflammatory disease of diarthrodial joints. It affects between 0.5% and 1% of the world's population, with women having a threefold prevalence. Using traditional therapy, the majority will develop moderate disability at 2 years, with 40% being unable to work at 5 years. The disease has a high cost in pain, disability, and deformity. Morbidity is high, with a reduced lifespan. The advent of new treatment paradigms has meant that disability has been reduced, orthopedic surgeries have a much reduced rheumatoid joint replacement case-load, and whilst still severe, the aim of therapy is to preserve normal lifestyle and work patterns.
This is achieved by the use of low-dose methotrexate, leflunomide, or sulphasalazine, followed by biologic therapies, mainly anti-tumor necrosis factor (anti-TNF-α), anti-B cell (anti-CD20), recombinant human IL-1 receptor antagonist (rhIL-1ra), or anti-interleukin-6 (anti-IL-6). There remains a severe problem that despite these regimes a significant proportion (up to 40% for anti-TNF-α) do not respond. In addition, these treatments are expensive in their own right, and heavy on clinical resources for administration and monitoring. There is thus a continuing requirement for the development of improved therapeutics through drug discovery and further development of current therapeutics and their targets. A detailed understanding of the pathogenic mechanisms of RA are also required to fulfill these aims. Animal models of rheumatic disease continue to play a significant role in this process.