Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic and debilitating inflammatory disease that causes pain, stiffness, swelling and limitation in the motion and function of multiple joints, which may eventually become deformed. These symptoms can make even simple activities, such as walking, difficult to manage. RA may also cause inflammation of other organs. The exact cause of RA is unknown, but the body's immune system attacks the synovium, the tissue that lines the joints. More than three million Americans suffer from RA. Although therapy has improved dramatically over the last 25 years, there is still no single therapy that is effective for all patients.

Treatment of RA can be divided into Disease-Modifying Antirheumatic Drugs (DMARDs), anti-inflammatory agents and analgesics. DMARDs have been found to produce durable remissions and delay or halt disease progression. Anti-inflammatories and analgesics improve pain and stiffness but do not prevent joint damage or slow the disease progression. Small molecule DMARDs, such as methotrexate, have anti-inflammatory and bone-sparing effects but their general suppression of the immune system leads to increased risk of infection. Steroids may provide relief during a disease flare but they also have serious side effects including high blood pressure, osteoporosis, reduced ability to fight infections, mood swings, diabetes mellitus and gastric ulcers. Newer biological DMARD agents include anti-TNF treatment and other biologic therapies. Approved by the FDA to treat moderate-to-severe RA that has not responded to one or more of the traditional DMARD, these agents must be given by intravenous infusion or subcutaneous injection. Due to their broad immunosuppressive effects, their use may lead to serious side effects including serious infections, such as tuberculosis and an increased risk of lymphoma.

During the development and progression of RA, the recruitment of immune cells, both innate and adaptive, into affected joints plays a key role in the inflammatory process and the ensuing joint destruction. There is strong evidence implicating CCR1 in the pathology of RA, including the presence of high levels of superactivated ligands of CCR1 in synovial fluids from RA patients and the increased expression of CCR1 on monocyte/macrophages found in arthritic joints. In addition, CCR1 may play a role in the formation of bone-destroying osteoclasts, a process that may contribute to the destruction of bone commonly seen in RA.

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