Rheumatoid Arthritis- -General Overview- Part I

(722/07)- The National Health Interview Survey for 2003-2005 indicates that an estimated 21.6% of the adult U. S. population (46.4 million persons) had a doctor-diagnosed arthritis, and 8.3% (17.4 million) had arthritis-attributable activity limitations. Women, older adults, persons with little education, or those who are obese, overweight or physically inactive are more likely to be effected. (CDC MMWR 2006; 55:1089-1092)

(3/7/03)- An FDA panel of experts recommended that more safety information needs to be added to the labels of certain rheumatoid arthritis drugs because of rare cases of serious side effects. About two million Americans suffer from rheumatoid arthritis. The original standard chemical treatment for RA was a cancer drug called methotrexate. The next generation of treatment for RA after methotrexate became Arava, a chemical that blocks the overproduction of immune cells that inflame joints. Aventis SA's Arava became the next chemical drug of choice in fighting RA

Beginning in 1998 however the next generation of RA drugs were those drugs that sop up the different inflammation-causing protein tumor necrosis factor (TNF). The three best known drugs in this category are Johnson & Johnson's Remicade, Amgen's Enbrel, and the most recent addition to the group Abbott Labs' Humira. The FDA has always warned however of the serious risks associated with these drugs.

Arva patients were found to suffer a higher rate of liver damage and the drug could cause birth defects. The TNF drugs carry the warnings that they could suppress the immune system enough to cause severe, even deadly, infections and could increase the risk of cancer. The FDA has reports of 170 cases of lymphoma among users of TNF drugs. At a safety meeting held by the FDA in August 2001 in connection with Remicade and Enbrel ( Humira was not on the market at that time), the FDA said that the benefits of the drugs outweighed their risks.

According to a study reported on from the Mayo Clinic in Rochester, Minn.a high incidence of rheumatoid arthritis was found in patients who have damaged immune systems. Up until now it was thought that overactive immune systems were somehow involved in RA. According to Dr. Cornelia Weyand, a rheumatologist who led the study, "Until now we have thought that these patients had overactive immune systems which is why we have aggressively treated the symptoms of rheumatoid arthritis with medications that suppress the immune system". RA is classified as an autoimmune disease, because the immune system mistakenly attacks healthy tissue or the joints. The study found that the T-cells (immune cells programmed to recognize and attack invaders) were worn out in individuals who had RA. Dr. Weyand stated that further study is now needed to determine which came first the rheumatoid arthrititis or the exhausted immune system.

Rheumatoid Arthritis (RA), the most common type of arthritis, is found in about 0.8% of the adult population. Epidemiological studies indicate that it reaches its peak incidence during the fourth and fifth decade of adult life. It is more prevalent in females than males. It is a chronic inflammatory disease, which primarily affects the joints, but it can also damage pulmonary, ocular and vascular structures. An interesting observation has been that during pregnancy, women who had RA experience a lessening of symptoms.

The inflammation of the joints causes pain, swelling and stiffness. Morning stiffness is the problem cited that most effects the quality of life for the individual. Lambert et al showed that there is a correlation between the duration of morning stiffness and clinical measures of psychological well being and depression. The stiffness occurs mostly in hand joints, which leads to hand related disability i. e. trouble getting dressed, eating etc.

The disease process can affect the joint and its function, causing severe impairment. An important factor that may explain the difference in disability in patients with similar disease activity and impairment is the patient’s way of behavioral coping with the disease. Coping is a defined "as cognitive and behavioral efforts to manage specific external and/or internal demands that are appraised as taxing or exceeding the resources of the person". Passive, avoidant, wish-fulfilling fantasy, depressive stance etc. are related to poorer psychological adjustments. On the other hand, active, information seeking, cognitive restructuring, rational thinking all seem to help patients to adapt psychologically to the physical and emotional stressors of the disease.

Kotte showed that limiting the level of activity results in progressive loss of functional capacity. The patient’s behavioral reaction to pain may be an important predictor of the patient’s future physical well being. "Behavioral coping is not only related to current dexterity, but also has an effect on subsequent dexterity… Passive coping strategies predicted lower physical functioning 6 months later…Remaining active, in spite of the pain, has beneficial effects on future physical functioning."

Evidence suggests that Tumor Necrosis Factor (TNF) concentrations are increased in synovial fluids of persons with active RA, and increased plasma levels of TNF are associated with joint pain. This recognition has lead to the use of substances to specifically block the pathway of the disease. Given the compelling evidence that pro-inflammatory cytokines are involved in the pathogenesis of RA, interference with the cytokine cascade earlier in the course of the disease may be a therapeutic benefit.

The goals of Rheumatoid Arthritis treatment are to decrease pain and inflammation, preserve joint function and prevent deformity. Non drug treatment includes such general measures as rest together with a controlled program of physical therapy and exercise. Current drug therapy includes salicylates and other non-steroidal anti-inflammatory drugs; disease-modifying anti-rheumatic drugs (DMARDs), which include antimalarials, gold, penicillamine, methotrexate and azathioprime; corticosteroids; and analgesics. The two newest DMARDs, leflunomide and etanercept have recently been added to the therapeutic armentarium.

Nonsteroids are the traditional first-line drug treatment for rheumatoid arthritis. They relieve pain and suffering and reduce joint inflammation, but do not alter the disease progression and can cause gastric mucosal injury, thus calling for co-administration of other drugs.

The two new DMARDs not only ameliorate the signs and symptoms of rheumatoid arthritis and retard joint damage but also have well-tolerated side effect profiles. Research suggests the initiation of DMARDs should not be delayed for more than three months in any patient whose disease remains active despite adequate treatment of NSAID’s. Leflunomide is an oral agent and entanercept is administered parenterally.

Leflunomide (Arava), an immunosuppressive medication, inhibits mitochondrial enzyme involved in pyrimide synthesis. It also has anti-proliferation and anti-inflammatory effect. Most common adverse effects were diarrhea, respiratory infections, hair loss, rash, nausea, and increase risk of hepatotoxicity. This drug costs about $250 per month for chronic therapy, after the three day loading which costs $125.

Etanercept, a tumor necrosis factor (TNF) inhibitor, blocks its interaction with cell surface TNF receptors, and thus inhibits the inflammatory process of rheumatoid arthritis and the resulting joint pathology. Response to medication usually occurs in one to two weeks after initiation of therapy and nearly always occurs within three months. It improves joint pain and swelling and morning stiffness. It is injected subcutaneously two times per week. Adverse events include respiratory infections, headache, and rhinitis. Its cost is approximately $110 per month.

The newest drug that the FDA is considering is Infliximar (Remicade) used for Chrohn’s disease. It is a monoclonal antibody that neutralizes the activity of TNF alpha, reducing the infiltration of inflammatory cells and reducing production of TNF alpha production. Adverse events noted include headache, nausea, abdominal pain, fatigue, fever and vomiting.

We are still a long way from preventing the expression of rheumatoid arthritis, especially in the elderly. Science is beginning to understand the mechanism and has become aware of the fact that there is more than one kind of rheumatoid arthritis. Many medications today are able to alleviate symptoms. We still have to await tomorrow’s discoveries to conquer this disabling disease.


Lambert VA, Lambert CE, Kipple GL, Mewshaw EA. Relationship among hardiness, social supports severity of illness and psychological well being in women with Rheumatoid Arthritis. Health are Women Int. 1990; 11:159-173.

Kitte FJ. The effects of limitation of activity upon the human body. JAMA 1966; 196:117-122.

Supplement to article on Rheumatoid Arthritis

In order to present the broadest range of information to our readers, we are adding this supplement to the article on Rheumatoid Arthritis. Much of the information available is anecdotal, but we feel is worth mentioning in light of the debilitating nature of this disorder.

The following is a list of measures that is found in a review of the literature to reduce arthritic pain for those who do not ascribe to use of pain killers. While no researcher has shown robust results in professional peer review journals, these measures are worth noting as a complement to more traditional pain relieving medications. Scattered citations continue to pop-up from time to time advocating one of these methods as valuable in pain management.

The following supplements have been suggested as influencing joint flexibility:

Niacinamide, Vitamin A, B1 , B6 and Vitamin E

The supplements mentioned below have been reported to have anti-inflammatory action:

Zinc, copper, selenium, manganese, panthothenic acid, flavonoids, tryptophan, sulfur, bee pollen, royal jelly and evening primrose.

We would suggest that individuals interested in getting more information about Rheumatoid Arthritis contact one of the organizations listed below.

  • Arthritis Associations
  • Rheumatoid Disease Foundation

    5106 Old Harding Rd.

    Franklin, TN 37064


    American Rheumatism Association

    17 Executive Drive NE, Suite 480

    Atlanta, GA 30329



    Arthritis Foundation

    1314 Spring St. NW

    Atlanta, GA 30309


    Association for People with Arthritis

    6 Commercial St.

    PO Box 954

    Hicksville, NY 11802



    National Osteoporosis Foundation

    1150 17th St. NW, Suite 500

    Washington, DC 20036




    See: Rheumatoid Arthritis Part II-TNF and Enbrel
    See: Rheumatoid Arthritis-Part III-Vioxx, Celebrex and the Elderly Who Have Ulcers
    See: Rheumatoid Arthritis-Part IV-General Overview-Part B

    Harold Rubin, MS, ABD, CRC, Guest Lecturer
    updated July 22, 2007

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