DOCTOR'S VIEW ARCHIVE
Perspectives of Interest On Arthritis Drugs & New Medications From 2003 Annual Scientific Meeting Of The American College of Rheumatology.
Scientists throughout the world are studying many promising areas of new treatment approaches for arthritis and rheumatic diseases. These areas include monoclonal antibody therapy that is directed against a special inflammation factor called the tumor necrosis factor (TNFalpha) (as described below regarding Remicade and Enbrel), and new TNF human antibodies. Also, new non-steroidal antiinflammatory drugs (NSAIDs), with mechanisms of action that are different from current drugs, are on the horizon. Genetic research and engineering are also likely to bring forth many new avenues of earlier diagnosis and treatment in the near future.
Below are perspectives on key research reports presented at the recent national meeting of the American College of Rheumatology:
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.
Remicade was also reported to be effective in juvenile ankylosing spondylitis.
Dr. Shiel's Perspective: Welcome news for this painful form of arthritis in children.
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.
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.
SLIDESHOW
What Is Rheumatoid Arthritis (RA)? Symptoms, Treatment, Diagnosis See SlideshowSeveral 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) 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.
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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) 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.)
Ultracet was found to be helpful in improving quality of life in fibromyalgia patients.
Dr. Shiel's Perspective: In treating patients with fibromyalgia it is important to not only relieve symptoms, but also to return quality of life. In other words, we don't simply want to knock out pain, we also want to resume function and normal daily activities. This research reports that Ultracet (tramadol/acetaminophen) actually improved the vitality of the patients in this study.
Arava reduces inflammation by suppressing the immune cells responsible for the inflammation. It does this by preventing the formation of DNA and RNA in the immune cells by inhibiting an enzyme (dihydroorotate dehydrogenase) that is necessary for the production of a critical component of DNA and RNA, pyrimidine (a nucleic acid).
Arava (leflunomide) was significantly effective in treating BOTH the skin inflammation (psoriasis) and the arthritis in patients with psoriatic arthritis.
Dr. Shiel's Perspective: Another fine addition to the ammunition chest against psoriatic arthritis.
Several research centers reported on new drugs for treating the elevated levels of uric acid that lead to gout.
Dr. Shiel's Perspective: This is exciting news for the gout field. There was especially promising news of an experimental drug called Y700 that can be used even in patients with kidney disease (where often other drugs cannot) because the drug is metabolized by the liver and not the kidneys like the traditional gout drug allopurinol.
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