Rheumatoid Arthritis

RA, a chronic inflammatory disease, is among the most debilitating of all forms of arthritis, causing pain, stiffness, swelling and limitation in the motion and function of multiple joints which may eventually become deformed. Sometimes these symptoms make even the simplest activities, such as walking, difficult to manage. The exact cause of RA is unknown, but it is believed to result from the body's immune system attacking the synovium, which is the tissue that lines a patient's joints. As of 2006, more than two million Americans suffer from RA, according to a report from Data Monitor. RA is two to three times more common in women than in men and generally strikes between the ages of 20 and 50, but it can also affect young children and adults older than age 50. Although therapy has improved dramatically over the last 25 years, there is still no cure and no single therapy that is effective for all patients.

Current treatment options for RA consist of corticosteroids such as prednisone, immunosuppressants such as methotrexate, TNF-alpha inhibitors such as Remicade, Humira and Cimzia, and other biologic agents such as Rituxan (rituximab) and Orencia (abatacept). Immunosuppressants have anti-inflammatory and bone-sparing effects, but the general suppression of the immune system leads to increased risk of infection. The use of these drugs may lead to mouth sores, stomach ulcers, and low white blood counts, and can cause severe toxicity of the liver and bone marrow, which require regular monitoring with blood testing. Corticosteroids may provide relief during a disease flare-up, but also have serious side effects, including high blood pressure, osteoporosis, reduced ability to fight infections, mood swings, diabetes mellitus and gastric ulcers.

Newer biologic agents have been approved by the FDA to treat moderate-to-severe RA in patients who have not responded to an adequate trial of one or more of the traditional courses of treatment. Biologic agents must be given by subcutaneous injection or by intravenous infusion. According to The Pain Practitioner, Spring 2011 Pharmacologic Approaches to Rheumatoid Arthritis, annual treatment cost with biologic agents range from $13,000 to $30,000 per patient depending on the drug used and the dose administered. Biologic agents are effective in some patients to treat the signs and symptoms of RA and the bone erosive effects of the disease. However, their use may lead to serious side effects including serious infections, tuberculosis, an increased risk of lymphoma and serious hypersensitivity reactions.

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; first, CCR1-expressing monocytes and macrophages are consistently found at high levels in the synovium of RA patients, and second, the C6 superagonists of CCR1, which are activated highly potent forms of certain CCR1 ligands, are consistently detected at high levels in synovial fluids from RA patients. 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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