Inside secrets of arthritis treatment: Biological weapons...
by Nathan Wei, MD, FACP, FACR
Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.
Click here: Second Opinion Arthritis Treatment Kit
The innovation that has revolutionized our approach to treating rheumatoid arthritis is the development of medicines that target the immunologic disturbance that causes rheumatoid arthritis.
The immune response in normal people consists of a delicate balance between cytokines that block inflammation and cytokines that promote inflammation.
Cytokines are messenger molecules that communicate between cells. When cytokines are produced, they are sent from one cell to another; they bind to a receptor on the cell and then cause the cell to do “something.” That “something” is generally to produce more destructive cytokines.
In diseases like rheumatoid arthritis, there is an imbalance favoring the overproduction and over activity of pro-inflammatory cytokines. The pro-inflammatory cytokine that seems to be the biggest culprit is tumor necrosis factor (TNF).
TNF causes many bad things to happen including the production of other pro-inflammatory cytokines (such as interleukin-1 [IL-1] and interleukin-6 [IL-6], damaging enzymes (like metalloproteases, collagenase, and prostaglandins) which degrade cartilage, and adhesion molecules that attract white blood cells into the area leading to more inflammation. Blood vessels also are stimulated to multiply which causes the lining of the joint to grow out of control and cause more destructive changes.
TNF is produced by white blood cells called macrophages, monocytes, and activated lymphocytes that invade the lining of the joint.
Theoretically, if it were possible to block the effects of TNF, it might be possible to slow down and even stop the progression of disease like rheumatoid arthritis. And that is what has happened.
Therapies designed to block the effect of TNF have led to the ability to put rheumatoid arthritis into remission.
The first such medicine to come to market was etanercept (Enbrel). This drug works by soaking up circulating TNF like a sponge. Etanercept is a receptor molecule that bonds TNF and prevents it from binding to cells and causing the release of other cytokines. It is given as a subcutaneous injection two times a week. In multiple clinical trials and in practice, it has been shown to reduce the signs and symptoms of disease as well as slow down the progression of disease.
The next anti-TNF drug was infliximab (Remicade). This is a drug that is a monoclonal (produced by one cell line therefore making it a “pure” preparation) antibody that is 75 per cent human and 25 per cent mouse. This antibody binds to TNF and prevents it from binding to cells and stimulating further cytokine release. This is given as an intravenous infusion. Since it has a long half-life (length of effect in the body), it is given less frequently than etanercept. The frequency of dosing varies but averages one dose every four to eight weeks.
Another anti-TNF drug is adulimumab (Humira). This is a purely human monoclonal antibody directed against TNF. Like etanercept, it is given as a subcutaneous injection every 2 weeks. It has a relatively long half life.
Two other anti-TNF products, certolizumab (Cimzia) and golimumab (Simponi) are also available.
So what can you expect with these drugs? First, they work for most people. Second, they probably should be used earlier rather than later. Remission is achieved better and faster by using these drugs early. Third, they all work better in combination with methotrexate. Fourth, not everybody responds. Sometimes the dose needs to be increased and sometimes despite dose escalation, patients won’t respond and should be tried on a different anti-TNF drug. Roughly 10-20 per cent of rheumatoid arthritis patients are anti-TNF failures.
Other diseases for which anti-TNF therapy has been used include psoriatic arthritis, Reiter’s disease, and ankylosing spondylitis.
Potential side effects include allergic reactions, injection site reactions, and worsening of infection (since they reduce the ability of the body to fight infection, patients with active respiratory or skin infection should not get this treatment).
Some patients with infliximab may suffer a lupus like syndrome. Reactivation of tuberculosis has also been reported with anti-TNF therapy, particularly infliximab. Fungal infections are also a significant risk with TNF inhibitors.
A demyelinating neurological disease similar to multiple sclerosis has been reported rarely with anti-TNF therapy.
Another biologic product, anakinra (Kineret) has also been approved by the FDA for rheumatoid arthritis. Anakinra blocks a different pro-inflammatory cytokine, interkeukin-1 (IL-1). The beneficial effect on rheumatoid arthritis is not that great and injection site reactions are common.
Another therapy is directed against B cells. B cells are lymphocytes that are responsible for activation of T cells and subsequent cytokine production. B cells are also responsible for producing antibodies that cause more inflammation. Theoretically by wiping out B cells, the pro-inflammatory cascade can be blocked. Rituximab is the drug that typifies this approach. It is given by intravenous infusion and is usually used in conjunction with steroids. Rituximab (Rituxan) was approved for use by the FDA in February 2006.
A therapy that blocks T-cell interaction at a co-stimulatory pathway was approved by the FDA in January 2006 for use in rheumatoid arthritis. That drug is abatacept (Orencia). It can be administered either intravenously or via the subcutaneous route.
In August, 2008, Actemra, a drug that blocks interleukin-6 was approved by the FDA. It is given intravenously every month starting at a dose of 4 mgs/kg and this can be increased to 8 mgs/kg.
And the search is on for other therapies that might alter the genes that code for the production of cytokines. Theoretically, if we can identify the “on-off” switch, we might be able to cure rheumatoid arthritis.
Get more information about biologics as well as...
• Insider arthritis tips that help you erase the pain and fatigue of rheumatoid arthritis almost overnight!
• Devastating ammunition against low back pain... discover 9 secrets!
• Ignored remedies that eliminate fibromyalgia symptoms quickly!
• Obsolete treatments for knee osteoarthritis that still are used... and may still work for you!
• The stiff penalties you face if you ignore this type of hip pain...
• 7 easy-to-implement neck pain remedies that work like a charm!
• And much more...
Click here Second Opinion Arthritis Treatment Kit
Return to arthritis home page.