Rheumatoid Arthritis Treatments

Of all of the inflammatory forms of arthritis, rheumatoid arthritis (RA) is the most common. It affects about 2 million Americans, about 60% of whom are women.  RA affects people of all ages including infants and children.

It is an autoimmune disorder characterized by chronic inflammation in the joints which causes pain, swelling, and stiffness. What is generally not understood is that it affects not only joints but internal organs as well.

Data has indicated that early aggressive treatment of RA can limit joint damage. RA 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 other co-morbid conditions.  People with RA are twice as likely to develop congestive heart failure is compared to those without RA. Cardiovascular disease is a major cause of mortality in patients with RA.

RA , if not treated aggressively, can cause permanent joint damage leading to deformity and loss of joint movement.  As a result, many people with RA experience limitations in their ability to perform daily activities which impacts quality of life.

woman-with-a-walkerRA is the most common cause 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 fewer than 50% of working age adults with RA are still employed 10 years after onset of the disease.

The cause of RA is unknown, but multiple genetic and environmental factors (infectious agents, reproductive status, and smoking) are thought to be involved.

When it comes to treatment, the primary goals are to relieve pain, swelling, and fatigue; improve joint function; slow down or stop joint damage; and prevent disability and disease-related morbidity.rub-hands

RA is a complex disease.  There are many cells, proteins, and processes involved in the genesis of RA.   T cells mediate joint damage both directly and indirectly by driving non-T  cells to release inflammatory cytokines.  Also,  B cells play a role in RA pathology by producing autoantibodies and triggering cytokine secretion by T cells as well as by acting as antigen-presenting cells (APCs) to trigger T-cell activation. This entire machinery is driven by multiple cytokines.

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 therapies in concert with methotrexate to effect remission as soon as possible.

A newer approach is to “treat to target.”  This means that a specific goal of remission is aimed for and adjustments in medications are made regularly in order to achieve it.target

Anti-inflammatory drugs- either non-steroidal drugs or low dose corticosteroids are an adjunctive therapy but are not considered as important as remission-inducing drugs. These drugs are initiated at the start of treatment to give the patient some relief- to serve as a “bridge” until the disease-modifying anti-rheumatic drugs (DMARDS) can kick in. Full therapeutic doses of non-steroidal anti-inflammatory drugs (NSAIDS) or prednisone in doses ranging from 5-10mgs/day are helpful for symptoms. Side effects related to an increase in cardiovascular events as well as gastrointestinal issues must be balanced against benefit.

Remission-inducing agents (DMARDS) 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 most commonly used is methotrexate.

Treatment options including combination DMARD therapy and  biologic response modifier are used by rheumatologists to induce remission.

Therapeutic agents including TNF antagonists and IL-6 inhibitors were developed to block cytokine-mediated processes.  Co-stimulatory pathway T-cell drugs were developed to inhibit T-cell mediated processes.  Elucidation of the role of B cells in the inflammation cascade has provided the rationale for the institution of B-cell targeted therapies.

Biologic drugs have revolutionized the treatment of rheumatoid arthritis and have permitted rheumatologists to achieve remission in many patients with RA.

Examples of biologics include the following: TNF inhibitors consist of Enbrel, Humira, Remicade, Cimzia, and Simponi.  Anti-interleukin 6 drugs are represented by Actemra.  The primary  T-cell drug is Orencia and the B-cell drug is Rituxan.  Many other drugs are in the pipeline.

In addition to the existing biologics, new oral kinase inhibitors (JAK and SYK) are exciting new drugs.

Objective measurement of remission include reduction in joint swelling and pain scores, improvement in health assessment and activities of daily living, reduction in blood measures of inflammation, and cessation of disease activity by magnetic resonance imaging.

Newer measurement criteria that will ensure uniformity of definition of remission are also being created.


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Arthritis Treatment

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