Reports from National Arthritis Meeting 2003

Perspectives Of Interest on Rheumatoid Arthritis from
2003 Annual Scientific Meeting of the American College of Rheumatology

• Introduction
• Newer Treatments
• Associated Conditions
• Disease Monitoring
• Patient Education
• Complications
• Osteoporosis Prevention Available, Underused

Introduction

Rheumatoid arthritis (RA) is an autoimmune disease that can cause chronic inflammation of the joints and other areas of the body. Rheumatoid arthritis can affect persons of all ages. Its cause is unknown. Rheumatoid arthritis is a chronic disease that is characterized by periods of disease flares and remissions. In RA, multiple joints are usually, but not always, affected in a symmetrical pattern (affecting both sides of the body). The chronic inflammation of RA can cause permanent joint destruction and deformity. The "rheumatoid factor" is an antibody blood test that can be found in 80 percent of patients with RA.

Rheumatoid arthritis is a common rheumatic disease, affecting more than two million people in the United States. The disease is three times more common in women than in men. It afflicts people of all races equally. The disease can begin at any age, but most often starts after age forty and before sixty. In some families, multiple members can be affected, suggesting a genetic basis for the disorder.

There is no known cure for RA. The treatment of RA optimally involves a combination of patient education, rest and exercise, joint protection, medications, and occasionally, surgery. Currently, doctors feel that the earlier patients with RA receive aggressive treatment, the better their long-term outcome.

Below are perspectives on key reports presented at the recent national meeting of the American College of Rheumatology:

Newer Treatments

Remicade (infliximab)

Remicade (infliximab) is an antibody that blocks the effects of tumor necrosis factor alpha (TNF-alpha). TNF-alpha is a substance made by cells of the body that has an important role in promoting inflammation. TNF promotes the inflammation and its associated fever and signs (pain, tenderness, and swelling) in several inflammatory conditions, including rheumatoid arthritis.  By blocking the action of TNF-alpha, infliximab reduces the signs and symptoms of inflammation and stops the progression of joint damage. Remicade is used to treat rheumatoid arthritis, Crohn's disease, and other serious forms of inflammation such as uveitis, psoriatic arthritis, and ankylosing spondylitis. Remicade is given by intravenous infusion over approximately 2 hours, usually every 4-8 weeks.

British researchers found that Remicade infusions could be safely administered at faster rates after the first 4 infusions if no reactions were noted in the first infusions. They also noted that stopping and restarting Remicade as a treatment did not result in any increase in toxicity.

Dr. Shiel's Perspective:   Exciting news for patients already using Remicade. It appears that they may not require the usual 2 hour rate of infusion after taking 4 doses of Remicade without side effects. Theoretically, Remicade might have the potential to cause sensitization. So that if Remicade were stopped and restarted at a much later date, there could  be an increased chance of allergic reaction. However according to this research, if, for whatever reason, Remicade treatment is interrupted, resumption of the drug at a later time does not come with an increased chance for an infusion reaction!

Researchers from the United Kingdom reported that patients whose rheumatoid arthritis is not controlled with Remicade can respond successfully to Enbrel.

Dr. Shiel's Perspective:   Well, this is very interesting. Since both Remicade and Enbrel block TNF as a key method of action, one might expect that switching from one drug to the other might not be effective. Wrong. The researchers point out that the reason for the benefit from switching might be related to the fact that they do differ slightly in their targets (Remicade binds to both a soluble form of TNF-alpha and to TNF-alpha bound to membranes of cells, while Enbrel binds to soluble TNF-alpha and to another chemical messenger lymphotoxin-alpha). Big words! They simply mean that if one fails on one TNF-blocking drug, it is rational to try another.

Remicade was reported as safe and effective in psoriasis and ankylosing spondylitis.

Dr. Shiel's Perspective:   Actually, rheumatologist have been using the drug for these patients for some time because of other preliminary positive reports in these conditions. It is good to have the support of this further long-term follow-up research.

Remicade was effective in treating sarcoidosis of the lungs and its accompanying toxic levels of calcium.

Dr. Shiel's Perspective:   Other reports of Remicade treatment of sarcoidosis are supported by this report. Remicade seems to have beneficial effects in many diseases that feature microscopic areas of tissue inflammation called granulomas. These diseases include Crohn's disease, Wegener's granulomatosis, and sarcoidosis.

Enbrel (etanercept)

Enbrel is an injectable blocker of tumor necrosis factor for treating rheumatoid arthritis and psoriatic arthritis. Tumor necrosis factor (TNF) is a protein that the body produces during the inflammatory response, which is the body's reaction to injury. TNF promotes the inflammation and its associated fever and signs (pain, tenderness, and swelling) in several inflammatory conditions, including rheumatoid arthritis. Enbrel is a synthetic (man-made) protein that binds to TNF. Enbrel thereby acts like a sponge to remove most of the TNF molecules from the joints and blood. This prevents TNF from promoting inflammation and the fever, pain, tenderness, and swelling of joints in patients with rheumatoid arthritis (and apparently other forms of inflammatory arthritis, such as psoriatic arthritis, ankylosing spondylitis, and juvenile arthritis-see below). Enbrel is given by subcutaneous injection with a needle and syringe twice weekly.

SLIDESHOW

What Is Rheumatoid Arthritis (RA)? Symptoms, Treatment, Diagnosis See Slideshow

Enbrel was found to be effective in a once weekly, 50 mg, dose!

Dr. Shiel's Perspective:   This is big news. Enbrel is now given by two 25 mg doses each week. Look for once weekly 50 mg dosing soon. Obviously, far more convenient for patients using Enbrel.

Several reports noted the safety and effectiveness of Enbrel for treating patients with psoriatic arthritis.

Dr. Shiel's Perspective:   Enbrel has been granted FDA approval for psoriatic arthritis this year because of previous reports that had similar results.

Enbrel was reported effective in treating ankylosing spondylitis.

Dr. Shiel's Perspective:   Look for FDA approval for this purpose soon.

Researchers from the United Kingdom reported that patients whose rheumatoid arthritis is not controlled with Remicade can respond successfully to Enbrel.

Dr. Shiel's Perspective:   Well this is very interesting. Since both Remicade and Enbrel block TNF as a key method of action, one might expect that switching from one drug to the other might not be effective. Wrong. The researchers point out that the reason for the benefit from switching might be related to the fact that they do differ slightly in their targets (Remicade binds to both a soluble form of TNF-alpha and to TNF-alpha bound to membranes of cells, while Enbrel binds to soluble TNF-alpha and to another chemical messenger lymphotoxin-alpha). Big words! They simply mean that if one fails on one TNF-blocking drug, it is rational to try another.

Enbrel for rheumatoid arthritis was reported to have sustained benefit and safety after 5 years of treatment.

Dr. Shiel's Perspective:   Great news to have long-term data that supports the concept that this drug actually safely stops rheumatoid arthritis in its tracks!

Humira (adalimumab)

Humira (adalimumab) is an antibody that blocks the effects of tumor necrosis factor alpha (TNF-alpha). TNF-alpha is a substance made by cells of the body that has an important role in promoting inflammation. TNF promotes the inflammation and its associated fever and signs (pain, tenderness, and swelling) in several inflammatory conditions, including rheumatoid arthritis. By blocking the action of TNF-alpha, adalimumab reduces the signs and symptoms of inflammation and stops the progression of joint damage. Humira is given by subcutaneous injection with a needle and syringe weekly or every other week.

Researchers from Los Angeles, Boston, San Diego, and Germany reported that the reduction of joint inflammation and improved function from Humira is often extremely rapid (as early as 1 week after starting treatment).

Dr. Shiel's Perspective: This report is consistent with the remarkable benefits in relieving joint swelling, pain, and stiffness that we often see with TNF-blocking drugs, such as Humira.

Several research groups reported that the beneficial effect Humira in quieting inflammation and stopping disease progression of rheumatoid arthritis was sustained over 5 years of study.

Dr. Shiel's Perspective: These reports are welcome news for patients with rheumatoid arthritis. It is reassuring that the initial, often dramatic, effect at stopping inflammation continues over years of treatment. It is very important to have these types of studies with newer medications.

Researchers from Germany reported that Humira is effective when used alone or in combination with methotrexate and that the blood levels of Humira are somewhat higher in patients taking methotrexate as well.

Dr. Shiel's Perspective: This report confirms what has been appreciated by rheumatologists for some time - that the benefits can be enhanced by combining methotrexate with TNF-blocking drugs. It also alludes to one explanation as to why, i.e., because blood levels of Humira are increased when taking  it with methotrexate.

Rituxan (rituximab)

Rituxan (rituximab) is an antibody that is used to treat lymphoma, cancer of the lymph nodes. It seems to be effective in treating autoimmune diseases like rheumatoid arthritis because it depletes B-cells, which are important cells of inflammation and in producing antibodies.

Rituxan was found to be beneficial in treating severe rheumatoid arthritis complicated by blood vessel inflammation (vasculitis) and cryoglobulinemia.

Dr. Shiel's Perspective: This report is one of many suggesting that Rituxan may offer an alternative in treating severe complications of rheumatoid arthritis. Rituxan would represent a novel approach as a treatment alternative in rheumatoid arthritis. (Incidentally, another paper at the meeting documented its safety in treating rheumatoid arthritis.)

Associated Conditions

Researchers from the University of Arizona reported that exercise was directly associated with a reduction in pain in patients with rheumatoid arthritis.

Dr. Shiel's Perspective: We rheumatologists (arthritis specialists) have long appreciated the benefits of exercise for diseases of the muscles and joints. This report emphasized not only the positive benefit of exercise on pain management, but also that this effect may increase over time!

Disease Monitoring

MRI scanning (magnetic resonance imaging) was shown by a number of research groups to be a very effective method for detecting the earliest forms of joint damage in inflammatory arthritis.

Dr. Shiel's Perspective: This method would actually allow physicians and patients a technique for deciding on appropriate treatments at the earliest possible time. This is actually extremely important in rheumatoid arthritis, where 70% of patients develop erosive joint damage within two to three years!

Citrulline antibody testing was reported in several papers to be helpful in diagnosing early rheumatoid arthritis.

Dr. Shiel's Perspective: Again, the earlier we hit this disease, the better. Furthermore, the presence of citrulline antibodies indicated rheumatoid arthritis with a greater than 95% accuracy! This is good!

Computer Web-based programs may be used effectively to monitor the function of patients with rheumatoid arthritis.

Dr. Shiel's Perspective: This means that arthritis specialists were able to use the computer as a platform for patients to register their symptoms and function over time. I have always believed that this would provide a valuable assistance to physicians in the care of patients with rheumatoid arthritis and am delighted that some groups are coming to the plate and starting to formulate standardized programs.

Patient Education

Rheumatology Web sites were found to provide valuable information for patients with rheumatoid arthritis.

Dr. Shiel's Perspective: What these researchers really did was to look deeply at the credibility of sites, such as MedicineNet.com, to determine that they are reasonably accurate and timely. I am happy to say that we are one of the finest sites in existence for rheumatology information!

Complications

Methotrexate toxicity of the liver was reported as extremely unusual.

Dr. Shiel's Perspective: This report from researchers in Brooklyn, University of Miami, and Vanderbilt University, confirms what most rheumatologists have noted - that methotrexate has become a favored medication for the treatment of early rheumatoid arthritis because it is relatively safe and it's toxicity is easy to monitor (with regular blood testing). Essentially methotrexate has become the "gold standard" DMARD as a result.

Vasculitis (inflammation and blockage of blood vessels), a serious complication of rheumatoid arthritis, has become extremely rare. (So rare that the British research team entitled the report "Rheumatoid vasculitis - following the Dodo.")  The researchers attribute the change to methotrexate treatment.

Dr. Shiel's Perspective: Terrific news! I agree that it has been some time since I have seen vasculitis in my patients with rheumatoid arthritis.

The rates of lymphoma for patients taking Humira were similar to rheumatoid arthritis patients of the same age and sex.

Dr. Shiel's Perspective:   What this research is really saying is that the rates of lymphoma are not increased in patients taking Humira. Humira theoretically might increase the chances for the development of lymphoma because of its central role in suppressing a portion of the immune system. This is good news for rheumatology care.

Heart disease, arteriosclerosis of the coronary arteries, was more common in women with rheumatoid arthritis than women of similar age without rheumatoid arthritis.

Dr. Shiel's Perspective: This report emphasizes the need for close general medical monitoring of patients with rheumatoid arthritis. Of note, the effect of rheumatoid arthritis on women became even more significant the longer the duration of their rheumatoid arthritis.

Osteoporosis Prevention Available, Underused

In a large study of patients seen in the setting of a rheumatic diseases division of a major university, one quarter of patients at risk for osteoporosis by taking cortisone medication for diseases such as rheumatoid arthritis and lupus were not receiving ANY form of prevention for osteoporosis.

Dr. Shiel's Perspective: The entire field of osteoporosis management has changed in recent years. Guidelines for the prevention of osteoporosis clearly emphasize that persons who are chronically taking cortisone medications should receive osteoporosis prevention counseling. This should include recommendations for diet, exercises, avoiding cigarette smoke, and when appropriate, estrogen replacement and/or medications to build bone density.

For more information, please visit the Rheumatoid Arthritis Center.

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