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Rheumatoid arthritis (RA) is a chronic, systemic disease that has complex genetic and environmental factors acting together to cause inflammation and damage. This occurs primarily in the synovium and joint tissues; however, there is also other organ involvement. The typical clinical features are swollen, painful joints and stiffness. Important extra-articular features include lung disease and cardiovascular disease. Other manifestations can include anemia, fatigue, skin nodules, neuropathy, ocular disease, splenomegaly, vasculitis and pleuropericarditis [1,2].
In many populations, there is a range of 0.5-1% prevalence, with a higher occurrence in Chippewa and Pima Indians and a lower occurrence in the Chinese and Japanese, supporting a genetic role in pathogenesis [2]. Women are affected up to three-times as much as men [3]. The annual incidence of RA has been shown to be approximately 30 per 100,000 population [3]. This disease can occur at any age, with peak onset between 30 and 55 years of age [3].
Joint damage can take place at disease onset, therefore, early aggressive therapy with the goal of remission is preferred by most clinicians to prevent disability, economic loss and mortality [4,5]. The course of disease is variable, with approximately 15-20% of patients having intermittent disease with a good prognosis [1]. Despite the wide use of disease-modifying antirheumatic drugs (DMARDs) and biologic agents in various combinations, some patients still have persistently active disease. Current recommendations by the American College of Rheumatology (ACR) deal with the indications for DMARDs and biologic agents. These guidelines account for screening for TB, side-effect monitoring, clinical response assessment, patient preference and cost. However, each patient is treated individually based on disease activity, prognostic signs and functional impairment. There is a strong recommendation to use a biologic agent only after failure of nonbiologic DMARDs unless high disease activity is present with poor prognostic signs [5,6].
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Small-molecule or nonbiologic DMARDs include methotrexate (MTX), leflunomide, sulfasalazine and hydroxychloroquine; they are all used as first-line agents (some in combination) in RA, with MTX being the dominant medication. Azathioprine, cyclosporine and gold agents are older and are used rarely these days. There is also a role for low-dose, long-term corticosteroids in some patients [7,8]. Those with persistently active disease after a trial of one DMARD are usually placed on...