Treatments for rheumatoid arthritis

by Nathan Wei, MD, FACP, FACR

Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.

Click here: Second Opinion Arthritis Treatment Kit

Information, in part, from the Arthritis Foundation and the American College of Rheumatology

Rheumatoid arthritis (RA) is the most common inflammatory type of arthritis.

It affects about 2 million Americans, about 70% of whom are women. RA is characterized by chronic inflammation in the joints which causes pain, swelling, and stiffness. RA can cause permanent joint damage leading to deformities and loss of joint movement. As a result, many people with RA experience limitations on their ability to perform daily activities; this has a major impact on quality of life. Studies have shown that early aggressive treatment of RA can limit joint damage.

Just as important is this… RA is a systemic disease and affects other body organs. It is a major contributor to morbidity and mortality. Mortality rates among people with RA are twice that of the general population and disease severity is an independent risk factor of mortality regardless of co-morbid conditions. The incidence of cardiovascular events in RA is independent of traditional cardiovascular disease in RA. People with RA are twice as likely to develop congestive heart failure is compared to those without RA.

A report by the Centers for Disease Control and Prevention describes arthritis as the most prevalent chronic condition. It is the most reported case of disability in the United States and the third leading cause of work limitations. Medical and indirect costs due to lost wages are estimated at $3 billion annually and less than 50% of working age adults with RA are still employed 10 years after onset of the disease.

The primary goals of therapy are to relieve pain, swelling, and fatigue; improve joint function; stop joint damage; and prevent disability and disease-related morbidity.

The cause of RA is unknown, but multiple genetic and environmental factors (infectious agents, reproductive status, decaffeinated coffee, and smoking) are thought to be involved. There is considerable discussion within the medical community at this time as to whether RA is one disease or several different diseases with common features. What is known is that the immune system plays an important role.

RA is a complex disease. There are many cells, molecules, and processes involved in the pathogenesis of RA. CD4+ T cells mediate joint damage both directly and indirectly by driving non-T effector cells to release inflammatory cytokines. In addition, B cells produce autoantibodies and triggering cytokine secretion by T cells as well as by acting as antigen-presenting cells (APCs) to trigger T-cell activation.

In the past the traditional treatment pyramid for rheumatoid arthritis was to start with anti-inflammatory drugs, move onto mild disease-modifying drugs (DMARDS), step up to more aggressive disease-modifying drugs if they didn’t work, and finally use powerful immunosuppressive drugs as a last resort. The treatment approach now is to stand the pyramid on its head and use more aggressive immunosuppressive drugs or biologic therapies in concert with methotrexate to effect remission as soon as possible.

Anti-inflammatory drugs- either non-steroidal drugs or low dose corticosteroids- remain an adjunctive therapy but are not considered as important as remittive drugs. These drugs are initiated at the start of treatment to give the patient some relief. Full therapeutic doses of non-steroidal anti-inflammatory drugs (NSAIDS) or prednisone in doses ranging from 5-10mgs/day are helpful for symptoms.

Remission-inducing agents are started at the same time or shortly thereafter. Besides methotrexate, other DMARD drugs include hydroxychloroquine (Plaquenil), azathioprine (Imuran), sulfasalazine (Azulfidine), cyclosporine (Sandimmune), and leflunomide (Arava). By far, the "workhorse" DMARD is methotrexate.

Treatment options including biologic drugs, disease-modifying anti-rheumatic drugs, and combination therapies have evolved from identification and elucidation of the processes and proteins involved in RA. For example, when T cells were identified as participants in inflammatory processes, therapeutic agents including TNF antagonists (Enbrel, Humira, Remicade, Cimzia, Simponi) and IL-6 inhibitors (Actemra) were developed to intervene in T-cell mediated processes. T-cell specific therapies such as Orencia also have their place. Clarification of the role of B cells in the inflammation cascade has provided the rationale for the use of of B-cell targeted therapies (Rituxan).

Oral kinase inhibitors (JAK and SYK) are also exciting new drugs.Xeljanz, a JAK inhibitor was approved by the FDA in 2012.

Objective measurement of “success” include reduction in joint swelling and pain scores, improvement in health assessment and activities of daily living, reduction in serum measures of inflammation, and cessation of disease activity by magnetic resonance imaging. The current treatment approach is called "treat to target". This means a patient needs to be evaluated monthly with the "target" being either remission or low disease activity.

The research community is actively involved in searching for biomarkers to identify at risk populations and evaluate treatment effectiveness as well as defining inadequate response to therapy so that treatment may be customized to individual RA phenotypes.

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