Rheumatoid arthritis (RA) affects 1% of adults during their most productive years and can result in significant disability. The goals of therapy are to reduce pain, limit joint destruction, and preserve function.
In recent years, the armamentarium of agents that combat RA has greatly expanded. New biologic therapies that specifically target the immune response are now available. Although disease- modifying antirheumatic drugs (DMARDs) such as methotrexate(Drug information on methotrexate) remain the standard of care, these newer agents can be added to the regimen when monotherapy fails.
In this article, I offer general guidelines for selecting the safest and most effective regimens for your patients with RA. I also describe how to make best use of the newer therapies.
OVERVIEW Epidemiology.Women are affected by RA about 3 times as often as men. The presence of estrogen receptors on synovial cells and T cells suggests an important hormonal relationship. Estrogens(Drug information on estrogens) influence both T-cell survival and cytokine production.1 This relationship between estrogen and immune disease may explain the increased prevalence of RA in women.
RA appears to be genetically linked, with higher concordance in monozygotic than dizygotic twins.2 One genotype of HLA-DRB chains appears to be a marker for RA.3 Approximately 10% of patients with RA have an affected first-degree relative.
Pathophysiology. RA is characterized by synovial inflammation and progressive erosion of cartilage and bone. The process begins with the activation of T cells, which results in proliferation of synovial cells, activation of proinflammatory cells from the bone marrow, and secretion of cytokines (including interleukin [IL]-1 and tumor necrosis factor α [TNF-α]) by macrophages and fibroblast-like synovial cells.4 Many therapies for RA-including corticosteroids and TNF and IL-1 antagonists-directly inhibit proinflammatory cytokine activities.
Disease progression. Symptoms of RA typically develop between the third and sixth decades of life. Significant joint abnormality and disability occur within the first few years of disease. 5,6 Eighty-three percent of patients with RA experience joint-space narrowing, and 67% have joint erosions with- in the first 2 years (Figure).2 After 5 years, joint erosions can be seen radiographically in 73% of patients.7 After 18 years, all patients have joint-space narrowing, 97% have joint erosions, and 41% have malalignment.7
Economic impact. Patients with RA begin to incur significant costs early in the course of illness. A study of patients with newly diagnosed active RA that evaluated costs during the first 6 months of illness showed that medical costs averaged $200 a month.8,9 Patients lost an average of 3.8 workdays monthly, at an indirect cost of $281.10 Eighteen percent became work-disabled during the first 6 months of illness. Work disability increased to about 60% after 10 years of illness.10
INITIAL EVALUATION The American College of Rheumatology (ACR) classification criteria (Table 1) can help guide clinical diagnosis.11 Laboratory testing is also useful in diagnosis, as well as in assessing prognosis and in monitoring the response to therapy. Rheumatoid factor-autoantibodies found in most patients with RA-may also be present in other rheumatologic conditions (eg, lupus erythematosus and Sjögren syndrome) and infectious illnesses (eg, malaria and rubella). A high rheumatoid factor titer in patients with RA is associated with more aggressive disease, greater joint destruction, and greater functional disability.12,13 The Creactive protein (CRP) level and erythrocyte sedimentation rate (ESR) are markers of the acute phase response. Elevations in CRP level and ESR also correlate with bone destruction.14
Evaluation includes an assessment of comorbid illness and lifestyle factors that may aggravate RA (Algorithm). Frequently associated comorbid conditions that may be exacerbated by either the pathophysiologic mechanisms that underlie RA or by its treatment include infection, renal insufficiency, cardiovascular disease, chronic pulmonary disease, peptic ulcer disease, and lymphoproliferative disease.15,16 Psychological distress also increases disability associated with RA; symptoms of anxiety, depression, and hopelessness need to be identified and treated.17-19
Cigarette smoking is associated with an increased risk of RA. Longer duration of smoking is linked to greater risk, and heavier use is associated with more serious symptoms and bony erosions.20-22 Obesity is also a risk factor, since adipose tissue releases proinflammatory substances, including IL-6, TNF-α, and CRP.23