Rheumatoid arthritis (RA) is a chronic, degenerative autoimmune disease that affects 1% to 2% of the U.S. population. It occurs more often in women than in men, and there is no racial predilection. The onset is usually during the fourth and fifth decade of life; 80% of all new patients with RA are between 35 and 50 years of age.

RA is characterized by joint inflammation and degeneration, which leads to joint deformity and immobility. Although joint manifestations are seen as the hallmark features of RA, extra-articular manifestations can occur; these include rheumatoid nodules, vasculitis, eye inflammation, neurological dysfunction, cardiopulmonary disease, and spleno-megaly.
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Although RA can appear abruptly, its onset is usually insidious or subtle, occurring over a period of weeks to months. The prodromal period is characterized by fatigue, weakness, low-grade fever, anorexia, and arthralgias. Joint involvement, which may be preceded by stiffness and myalgias, is generally symmetrical and most commonly involves the small joints of the hands, wrists, and feet. RA is not limited to these smaller joints, however, and may be present in the knees, spine, elbow, ankle, and temporo-mandibular joint. As the disease progresses, joint deformities lead to alterations in strength and motor movements. These changes result in functional impairment and are associated with increased morbidity and mortality.

The specific pathogenic mechanism of RA remains unclear, although one theory suggests that exogenous or endogenous antigenic triggers, acting in the presence of a genetic predisposition, initiate a self-perpetuating autoimmune response within the synovial compart-ment. This series of events leads to an increased presence of lymphocytes, macrophages, and fibroblasts within the synovium with a corresponding increase in the number of cytokines and chemo-kines produced, such as interferon-gamma (IFN-y), interleukin-1 (IL-1), and tumor necrosis factor (TNF). The increased presence of these pro-inflammatory agents contributes to the clinical manifestations of RA, including synovial tissue inflammation, synovial fluid inflammation, and synovial proliferation, resulting in subsequent cartilage and bone damage.

Pharmacological strategies used in the treatment of RA address two goals: (1) alleviating symptoms associated with the disease and (2) altering the progressive nature of the disease.

Alleviation of symptoms is achieved through the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids. The effort to slow the progression of RA includes disease-modifying  anti-rheumatic  drugs (DMARDs), which include gold salts, D-penicillamine, hydroxychloroquine sulfate (Plaquenil, Sanofi Synthelabo), (Prometheus Laboratories),  (Sandimmune, Novartis) (Azulfidine canadian, Pfizer) and (MTX) (Wyeth; Trexall, Barr). Advances in our understanding of the pathogenesis of RA have more recently prompted the use of agents that target the pathogenic elements of the disease. These agents include those that target TNF, such as infliximab (Remicade, Centocor), etanercept (Enbrel, Amgen/ Wyeth), and adalimumab (Humira, Abbott), and anakinra (Kineret, Amgen), which targets IL-1.

Treatment of RA is successful in approximately two thirds of patients, leaving the remaining one third to suffer from the debilitating effects of the disease. New hope for these patients was recently discussed in anecdotal reports of remission of RA in patients receiving the monoclonal antibody rituximab (Rit-uxan, Biogen/Genentech) as a therapy for lymphoma. These reports led to randomized, double-blind, controlled trials that showed major clinical benefit. Rituximab offers a new approach to the management of RA by targeting the cellular elements (i.e., B cells) that function as a driving force behind the autoimmune responses seen in RA.