Rheumatoid Arthritis

Rheumatoid Arthritis:
New therapies and disease management requirements

Rheumatoid Arthritis (RA) is one of the most common and serious forms of arthritis. It is an autoimmune disease in which the body’s immune system attacks the joints, causing inflammation and erosion. RA causes more than 9 million physician visits and 250,000 hospitalizations a year. Currently, 2.1 million Americans suffer from RA, which tends to strike patients in their most productive years. The US pharmaceutical market for treating RA now exceeds $5 billion dollars annually, and is expected to grow to at least $10 billion by 2010. Despite growth in the number of therapies for RA, effective diagnosis and optimal management of the disease remains an elusive objective.

RA is a chronic disease, characterized by inflammation of the lining, or synovium, of the joints. It can lead to long-term joint damage, resulting in chronic pain, loss of function and disability. The images to the right depict the differences between a healthy joint and one with RA. Most patients experience a chronic fluctuating course of disease that, despite therapy, may result in progressive joint destruction, deformity, disability, and even premature death. Disability from RA causes major economic loss and can have a profound impact on families.

The term rheumatoid disease may more properly define RA, particularly because of systemic involvement. Extra articular and systemic manifestations are common in RA patients. For example, cardiopulmonary manifestations of RA may develop, including pleuritis and pericarditis with effusions. These events are rarely diagnosed clinically, but asymptomatic pericarditis is found in 40-50% of autopsied RA patients. Additionally, patients may develop interstitial pneumonitis, pulmonary fibrosis, renal abnormalities such as proteinuria, or rheumatoid vasculitis of the organs. About 15-20% of RA patients also develop secondary Sjögren’s syndrome, which is characterized by kerato-conjunctivitis sicca.

There are no definitive diagnostic tests today for RA. The most important factors in establishing a diagnosis is a physical examination and patient history. X-rays, particularly of the hands, are frequently considered in the diagnosis of RA. Depending on disease severity, however, thinning of the bones may not be discernible on ordinary X-ray images for several months or years after symptoms of the disease appear. The clinical laboratory tests that have historically been used to test for rheumatoid arthritis, such as rheumatoid factor (RF), C-reactive protein (CRP), and, more recently, anti-CCP, can help support a clinical diagnosis of RA, but none is independently conclusive.

The treatment of RA has changed dramatically over the last decade, and an armamentarium of new, effective agents has significantly improved the every day life of millions of patients affected by this debilitating disease. Methotrexate remains the core treatment of patients with rheumatoid arthritis, however, patients often experience dose limiting toxicity with this therapy. Additionally, methotrexate is ineffective at controlling disease activity in up to 50% of patients. Second line therapies include leflunomide as well as newer monoclonal antibodies directed against Tumor Necrosis Factor alpha and other targets. These newer biologic therapies include infliximab, etanercept, adalimumab, rituximab and abatacept, all of which are typically administered in combination with methotrexate.

The imminent role of Personalized Medicine

Despite the influx of new therapeutic options for RA patients, disease progression is not halted and chronic symptoms are not relieved in a significant proportion of patients treated with current disease modifying anti-arthritic drugs, including the highly expensive new monoclonal antibodies directed against inflammatory cytokines. It is now well recognized that the standard of care “one drug fits all” approach is less than effective at optimizing health outcomes, and that a paradigm shift towards the “right drug for the right patient at the right dose” will provide incremental health benefits in a more cost effective manner.

The future of RA treatment, and, indeed, the future of medicine, is powerful, customized, medicine based on each patient’s needs and DNA.

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