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Rheumatoid Arthritis

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of rheumatoid arthritis.

Alternative Names

Corticosteroids; Immunosuppressant Drugs; Nonsteroidal Anti-inflammatory Drugs, or NSAIDs

Treatment

The treatment of rheumatoid arthritis involves medications and lifestyle changes.

General Guidelines for Drug Treatments

Many drugs are used for managing the pain and slowing the progression of rheumatoid arthritis, but no medical program has been found to cure the disease. Some experts believe that no single drug will ever cure rheumatoid arthritis because of the different immune systems and many other factors that affect the disease at various times. The goals of drug treatment for rheumatoid arthritis are the following:

  • To reduce inflammation.
  • Prevent damage to the bones and ligaments of the joint.
  • Preserve movement.
  • To be as inexpensive and as free from side effects as possible over the long term.

Drug Categories Used for Rheumatoid Arthritis

The drug categories used for RA are generally defines as follows:

  • The least potent drugs used for RA are nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs relieve pain by reducing inflammation, but do not contain steroids, powerful anti-inflammatory hormones.
  • The drugs traditionally used as second-line therapy are categorized as disease-modifying antirheumatic drugs (DMARDs). They do not have any common properties other than their ability to slow down the progression of rheumatoid arthritis. Many were used for other diseases and were found accidentally to help RA. Such drugs are more effective than NSAIDs but also have more side effects.
  • Corticosteroids, or steroids, are powerful anti-inflammatory agents. They are often put into a different category from the DMARDs, because these drugs may be used for different aspects of the disease.
  • Certain immunosuppressants are used as third-line drugs for disease that recurs or does not respond to second-line agents. They inhibit the immune system and have potentially very serious side effects.
  • New drugs that modify or block destructive immune factors are also now available. Tumor-necrosis factor (TNF) modifiers are major breakthroughs in the treatment of RA. The current agents include infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira). An interleukin-1 antagonist, anakinra (Kineret), has also been approved.

All of these drugs have potentially toxic side effects.

Treatment Approaches

The question of how early and how aggressively to treat RA is currently the subject of great debate. Studies have found less joint damage in patients with early, aggressive treatment, particularly with the use of DMARDs and TNF modifiers. Some experts believe that with early aggressive therapy, remissions may be so successful that RA might even be considered potentially curable. There is also evidence that early use of DMARDs may help protect against heart problems, which can be major complications of RA.

It is not fully clear, however, which patients should receive such early aggressive treatment. Of all patients with RA, some will go into remission and remain in remission for the length of their lives even in the absence of treatment, while others will go on to develop active, sometimes severe RA. European researchers found that if the disease subsides within three months after diagnosis, patients tend to stay in remission. If disease persists beyond three months, it is likely to persist long-term. At this time, the evidence suggests that people who are most likely to develop severe disease have the following characteristics:

  • Positive rheumatoid factor
  • Antibodies to CCP
  • Early erosive damage to joints
  • Persistent inflammation despite steroids or NSAIDs

These indicators are not absolute, and further study is underway to better determine who is at greatest risk of disease progression, and how beneficial early aggressive therapy is among different patient populations. Nevertheless, new early arthritis centers are encouraging people with the earliest symptoms to seek help from arthritis specialists, with the hope of detecting and treating the disease before symptoms progress.

Layered or Step Approach

Given the recent evidence and the important questions still outstanding, a layered, step-up or step-down approach probably describes the manner in which therapies are administered in the majority of cases today. One or more agents may be given for a period of time; depending on symptoms one or more may be added or dropped as needed.

Because there are so many potential combinations, it is not possible to list a typical regimen. Numerous variables affects which drugs may be prescribed at a given time, including the severity of disease, how well a particular agent has worked for an individual, patient preferences regarding pills or injections, side effects, and other factors.

Overall, however, physicians are increasingly using stronger medications first, based on studies showing that joint damage can be slowed or stopped with such early interventions. Combinations of DMARDs (especially methotrexate) and biological agents (TNF modifiers) are considered by far the most effective therapies.

Inverted Pyramidal Approach.Some experts recommend a so-called inverted pyramidapproach for patients with moderate to severe RA that uses the most aggressive agents first. The method uses one of two approaches, depending on severity:

  • Some patients start out immediately with DMARDs, with or without NSAIDs.
  • Others start DMARDs after three months if NSAIDs have not relieved symptoms.

A TNF-modifier may be added if patients do not show 70 80% improvement after full-dose methotrexate therapy.

Pyramidal Approach. A pyramidal approach may be very useful for some RA patients, particularly those with benign, or type 1, rheumatoid arthritis:

  • The least powerful drugs (usually NSAIDs) are used first to avoid toxic effects.
  • If NSAIDs are still not effective after about four to six weeks, more potent drugs are added to the regimen.
  • Gradually, stronger and stronger drugs are used until the disease is under control.
  • Working through the pyramid, drug by drug, generally takes five to eight years.

This pyramidal approach, while effective for type 1 RA, is not generally recommended now for type 2 RA for the following reasons:

  • It fails to prevent the progression to joint destruction and debility in people with severe type 2 RA.
  • Much of the damage in type 2 RA occurs within the first two years, when under the pyramidal approach, NSAIDs are being used, which have no effect against joint damage. And, over time, the side effects of NSAIDs can even be as severe as those of some DMARDs.
  • In one study, only 18% of RA patients using the pyramidal approach achieved an initial remission, and less than 2% had remissions that lasted more than three years.
  • The association between lymphoma and immune system abnormalities in rheumatoid arthritis is also a possible argument for early aggressive treatment that inhibits immune factors.

On a cautionary note, over-treating a benign case can be almost as damaging as undertreating a serious case. Certain factors that might warrant against the aggressive approach include the following:

  • Male gender.
  • Older age.
  • Lack of genetic markers.
  • An acute onset of the disease.
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