Hotline Archive - Update on New Agents for Arthritis
March 1999
Celebrex (celecoxib)
Patient Information
Celebrex (celecoxib) has recently been approved by the FDA and is currently available on the market. It is the first of a new class of drugs called COX-2 specific inhibitors. It is being marketed as a drug that will reduce pain and inflammation in arthritis while being less likely to cause stomach problems, such as ulcers, than current non-steroidal anti-inflammatory drugs (NSAIDs).
One of the major ways in which NSAIDs work is to inhibit enzymes called cyclo-oxygenase (abbreviated COX). There are two types of cyclo-oxygenase: COX-1 and COX-2. COX-1 enzymes are present under normal conditions in many tissues of the body and are beneficial. For example, they may protect the stomach lining and maintain kidney blood flow. COX-2 enzymes are produced during inflammation and contribute to pain and swelling in arthritic conditions.
Currently, all other NSAIDs available to the public inhibit both COX-1 and COX-2 enzymes. As a result, all other NSAIDs reduce inflammation and pain in many people but also cause stomach-related side effects such as ulcers and heartburn as well as kidney problems.
Doctors know that some patients who take nonspecific NSAIDs for arthritic pain have a higher risk of stomach-related problems. Such people have already had ulcers, are older, or have other medical problems. There are strategies that doctors may use today that can reduce the side effects and permit some people to keep taking the nonspecific NSAIDs. For example, drugs such as misoprostol (Cytotec) and omeprazole (Prilosec) may reduce stomach ulcers in people who take nonspecific NSAIDs.
In clinical studies lasting up to six months, patients who took celecoxib were observed by endoscopy tubes inserted into their stomachs to have fewer stomach ulcers than patients who took other NSAIDs. It is not known whether this decrease in the number of ulcers will be associated with a lower frequency of complications of ulcers such as bleeding.
The studies show that celecoxib works about as well as other NSAIDs such as ibuprofen or naproxen for arthritis pain. Celecoxib costs 4 to 5 times as much as generic ibuprofen or naproxen.
For non-inflammatory conditions such as low back pain or muscle aches, analgesics such as acetaminophen or low doses of ibuprofen are preferred because they are effective, usually safe, and inexpensive.
In most arthritis patients who have no major risk factors for gastro-intestinal side effects, the nonspecific NSAIDs may be taken relatively safely in low doses. If stomach distress does occur, other medications may be effective in calming symptoms and/or preventing ulcers.
Any patient who has active ulcer disease or GI bleeding problems, is on multiple medications, has serious medical disorders, or is quite elderly, should be encouraged to use non-pharmacologic approaches for their osteoarthritis if at all possible.
The exact role for celecoxib and other COX-2 specific inhibitors for the treatment of chronic arthritis pain and inflammation will emerge after more experience accumulates. Celecoxib is indicated for chronic arthritis pain with or without inflammation.
March 30, 1999
The Communications and Marketing Committee of the American College of Rheumatology
Hotline is provided by the ACR Communications and Marketing Committee as a service to members. This Hotline reflects the views of the author(s) and does not represent a position statement of the College.
Update on New Agents for Rheumatoid Arthritis
Enbrel (etanercept)
Patient Information
In 1998, a new agent, Enbrel (etanercept), was approved by the FDA for use in the treatment of adult rheumatoid arthritis (RA). It is now available on the market. Etanercept is the first of a new class of drugs that target specific biologic functions in RA — in this case, the action of tumor necrosis factor (TNF).
TNF is a chemical produced by the immune system that is normally beneficial to health. If too much TNF is produced, however, it triggers a cascade of inflammatory reactions in the joint. These reactions lead to joint swelling and pain and eventual damage. TNF works by attaching to chemical receptors on the surface of cells which then produce other chemicals to cause inflammation.
Etanercept is a bio-engineered, duplicate copy of the natural receptor for TNF. When given by injection, it "floods" the body with artificial receptors, acting like a sponge to remove most TNF molecules from the joints and blood. This action prevents inflammation and presumably damage in joints.
In clinical studies lasting up to 18 months, etanercept significantly decreased joint swelling and pain, improved function, and decreased laboratory abnormalities of inflammation in the majority of patients with active RA. Etanercept provided additional benefit to some patients who were already taking methotrexate.
Etanercept is given twice weekly by subcutaneous injection (under the skin). Patients may be able to perform this procedure themselves at home.
Some patients experience injection site reactions. Nothing is known about potential long-term (beyond two years) benefit or side effects. There is some theoretical concern that blockade of TNF action may affect the ability to fight certain infections. Whether there is a risk of developing tumors of the lymph nodes with chronic therapy is unknown.
Etanercept was approved by the FDA for patients who have been unsuccessfully treated with one or more disease-modifying anti-rheumatic drugs (DMARDs). It is not recommended for pregnant or nursing women.
Etanercept costs 15 to 20 times as much as generic methotrexate. It could be used when traditional DMARDs have failed, and can be used in combination with methotrexate.
March 30, 1999
The Communications and Marketing Committee of the American College of Rheumatology
Hotline is provided by the ACR Communications and Marketing Committee as a service to members. This Hotline reflects the views of the author(s) and does not represent a position statement of the College.
Arava (leflunomide)
Patient Information
In 1998, a new agent, Arava (leflunomide), was approved by the FDA for use in the treatment of adult rheumatoid arthritis (RA). It is now available on the market.
Leflunomide inhibits an enzyme that participates in inflammation in the joints of people with RA. Clinical studies lasting up to 12 months demonstrate that leflunomide improves the signs and symptoms of RA and may slow down joint damage as seen on x-rays. In two studies, leflunomide’s effectiveness was similar to sulfasalazine and methotrexate, two disease-modifying anti-rheumatic drugs (DMARDs) that have been widely used in RA for many years.
Leflunomide may cause diarrhea, hair loss, rash, and, rarely, liver disease. It is toxic to fetuses and should not be used in pregnant or nursing women, and women and men not using reliable birth control methods, or in children. Its long-term side effects are unknown.
Leflunomide costs 4 to 5 times as much as generic methotrexate and is indicated for patients with active rheumatoid arthritis.
March 30, 1999
The Communications and Marketing Committee of the American College of Rheumatology
Hotline is provided by the ACR Communications and Marketing Committee as a service to members. This Hotline reflects the views of the author(s) and does not represent a position statement of the College.
