They act by binding T.N.F.-alpha one of the dominant cytokines or proteins that play an important role in inflammation, responsible for pain,swelling, and damage to joints affected by RA.

 

 Cytokines feed on TNF alpha that's the only thing they bind to. The effect is  when they're injected into a patient is to mop up or absorb excess amounts  of  TNF alpha (Enbrel).

 

There are two current biologic response modifiers,(BRMs) Enbrel and Remicade available for RA treatment. People with RA tend to overproduce  T.N.F.alpha(tumour necrosis factor).

 

Remicade (Infliximab) is made from a specially developed antibody (monoclonal antibody) called cA2 which acts against TNF alpha It requires intravenous infusions,it takes about 2 hrs. The first infusion is repeated after 2 weeks,then one month later,every two months after that, used alone or in combination with Methotrexate.

 

The combination halts progression of joint damage,than MTX alone. Many patients, however, develop antibodies to Infliximab itself, and some studies indicate that the benefits dissipate when the drug is discontinued. 

 

 Never-the- less in one study benefits lasted for at least 2 years after stopping the drug. In another study reported that joint progression of the disease was halted. In another group of patients with severe RA it may have controlled the disease process better than any other therapies to date.

 

Side effects are similar to Etanercept.People prone to infection must be cautioned. Remicade is what's called monoclonal antibody to TNF alpha-what that means  is  they have taken TNF alpha and they inject it into animals to make a antibody against it,purify it, humanize it,and the antibody is injected into the body. MTX-Remicade combination is usually used.

 

Etanercept (Enbrel) works by blocking a natural toxic substance produced by the body called tumor necrosis factor-alpha a major player in the disease process. It triggers much of the inflammation in the disease.

 

The progression of the disease was stopped in 72% of the patients getting twice-weekly injections of the drug for one year. By comparison, 60% fared this well when taking MTX pills the older standard medication.  

 

Enbrel is administered twice weekly by subcutaneous injection using a small needle Patient's prone to infection are not recommended,also T.B. or with nervous disorder such as M.L.S. Etanercept is a synthetic man made protein.

Arava used in conjunction with MTX or alone is a new  DMARDs drug developed,it retards joint damage and erosion and lessens the degree of narrowing of the space between the joints. Pregnant women are not advised to take Leflunomide. 

 

Arava is a immunosuppressive agent, whats  called a cell cytoactive drug. it works by blocking cell replication and cells that are rapidly dividing.In RA and other inflammatory conditions. These inflammatory cells are the area that are activated,and this is where the suppression occurs.

 

In a study,250 patients taking Leflunomide for 2 years showed continued to show significant improvement in performing daily activities. There were fewer side effects seen.

 

"Arava is just as good or better than Methotrexate" said one research-scientist.   N.B.--Patient reaction to a drug will be different in some situations.i.e., one drug will work for one patient and it may not be suitable for another).

Amgen Corp. (Kineret)has developed a synthetic protein that will bind to the receptor so that the interleukins can't bind,putting up a road-block of sorts to the painful responders.

 

One of them is IL-alpha  (Interlukin-1) which was recently approved by the FDA. Kineret may be useful for patients that have  tried and failed other DMARDs.   

 

Clinical trials has been done on combining biologics with Kineret,but the high incidence of undesired side effects,has led scientists working in the trials to conduct further trials to determine if it was due to dose related,and to determine at what dose the combination can be safely be employed.

 

Currently,combination therapy with Kineret and Biologics is not recommended for wide-general use.

 

Research  suggests that IL-1 is a primary mediator of bone and cartridge destruction in RA patients,whereas TNF-alpha appears to be the primary mediator of inflammation.

Remicade and Enbrel have been developed specifically,to combat the course of RA disease,a DMARDs medication.

The two biologic response modifiers are currently not covered by O.H.I.P. in Ontario--Saskatchewan and B.C. are the only provinces currently that pays for the medication. Due to the high cost of R&D the cost to the patient is in the $1000+ monthly category. I have heard of patients who have been relieved of pain and have complete mobility.

 

Some are on Enbrel only. I am told that this will not be the case with every patient and others will be treated with a combination medication.While some patients will not respond at all,to the new medication.

Research Scientists are able to access more information on the history and future course of the disease,important to the patient that was not known in the past. In the past,medications used to treat RA were "borrowed" from treating other diseases. Currently,there are new drugs in the research,and awaiting- approval stages.

Why is it that Canada is so far behind the U.S. in approving new drugs?When approved,the cost is so high that only a select minority have access to the new drugs.Joints once damaged cannot be reversed. Governments look at the short term and do not consider the greater future costs of treatment over the longer term.

 

In Canada health care is unequalized by province (biased on arthritic medication like the biologics). Meanwhile,the governments,both federal,and provincial boasts about "equitable health care to all Canadians-regardless of economic status".

Updates re-biotech drugs--BRMs: I was recently informed that the newer biologic response modifier drugs may be available to Canadian residents through government paid health plans when the current medication is ineffective.Many patients have applied,but they have been denied--"special access plan" in Ontario.

The added paper work to the practisioner is time consuming and the time to receive a "no" reply from the government health plan is even longer. The federal government approves a computer network for the armed services costing $200 million + that is so outdated that its non-operational.

 

Likewise the government approves  a state-of-the-art jet aircraft (for officials)costing millions but use 40 year old outdated and unreliable,helicopters for "sea rescue".

We as patients must become more active in political involvement,access to government spending and accountability. Aids,cancer,and some other chronic disease patients have full medical coverage. Why not RA patients? It is a simple case of descrimination, and stupidity on the part of bureaucrats.

The Prosorba Column treatment involves circulating a small amount of the patients blood through a coffee cup sized column that contains protein A a substance that binds and removes harmful antibodies and immune complexes.

 

The treated blood is then returned to the patient. Clinical trials are in progress in Toronto Canada by Medexus Inc.It is the only non-drug treatment approved by Health Canada to long time  RA patients who have not responded to other treatments.

 

The Prosorba Column offers a unique non-drug alternative for patients who have failed on other therapies or who,for one reason or another, are concerned about traditional drug treatments,says C.E.O Bruce Clark-Medexus Inc. a Canadian developer.

 

The Prosorba Column has been used for more than a decade to treat an immune bleeding disorder known as Idiopathic Thrombocytoperic Purpura or ITP. It was approved for treatment of RA patients in the U.S. in 3/99.

 

A research team at University College in London England says it has discovered why the body defenses mistakenly attacks healthy tissues and joints in RA. Its cure focuses on B cells,white blood cells that defend the body against viruses and bacteria by making antibodies that attack the microbes. B cells can accidently make antibodies, that attack healthy tissues.

 

The treatment is based on drugs, predinisolone, cytoxan and another called mabthera (rituximub) that team up to remove specialized cells called B lymphocyte. Since they seem to have less risk in attacking them. After the diseased lymphocyte is destroyed, healthy cells replace them in a manner of months.

 

Dr. J. Kippel of the Arthritis Foundation says it look promising but further tests are required before it can be FDA approved.

 

Cytokines are crucial mediators of the inflammatory response in rheumatoid arthritis. Interleukin-1 (IL-1) is one such cytokine  that promotes inflammation. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring protein that blocks the binding of IL-1 to its receptors,thereby diminishing the inflammatory response. Anakinra is a recombinant human form of IL-Ra .

 

Thousand Oaks,CA---11/14/01--Amgen announced that the FDA has approved Kineret, (Anakinra) for the reduction in signs and symptoms of moderately to severley active RA in adult patients who have failed one or more DMARDs.

 

Kineret is the first direct and selective blocker of interleukin-1 (IL-1),a protein present in excess in RA patients. By blocking IL-1,Kineret inhibits the inflammatory response in RA including pain.

 

Approval of Kineret was based on a total of 2,932 patients studied in randomized,double-blinded,placebo-controlled clinical trials. Of the total patients,more than 2,600 were treated with Kineret.

 

Kineret,taken alone or in combination with other commonly used DMARD therapy, ( e.g..MTX)  improves the signs and symptoms of RA. Many clinical responses, including a decrease in inflammation and pain,were seen by the 4th week and most were seen by week 13.

 

After 6 months of therapy,38% of Kineret patients as compared with 22% of placebo patients achieved a 20% improvement in the ACR 20 criteria include a 20% improvement in the number of swollen and tender joints,plus a greater than or equal to 20% improvement in at least three of five of the following criteria:

 

Physician assessment of disease.

 

Patient assessment of disease,pain.

 

C-reactive protein (a general laboratory marker of inflammation).

 

 Health questionnaire assessment.

 

The most common side effect was a reaction at the site of injection, usually mild,characterized by redness,swelling and pain. There was a risk of serious infections (2 % in Kineret patients vs. 1% in placebo patients) in the clinical trials.

 

Although Kineret should be discontinued if a patient develops a infection,most patients can continue taking Kineret after their infection resolves. Kineret should not be used with TNF blocking agents etanercept or infliximab. Preliminary data suggest a higher incidence of serious infection (7%) and the occurance of neutropenia (3%) when Kineret is used with these agents.

 

Adalimurab (DE27)-- DE27 is the first human anti-tumor necrosis factor-alpha monoclonal antibody biologic drug. It differs from other "Chimeric" anti-TNF antibodies,which include varying amounts of genetric materials from other species,often from mice in the case of Remicade

 

. Current studies show that Adalimurab binds TNF-alpha in patients with RA and thereby turns off or lessens the inflammatory process in  patients with RA. DE27 shares the property of Enbrel and Remicade in that it is an approach to inhibit TNF.

 

It is like Remicade in that it is a monoclonal antibody. It differs in that it is a humanized antibody.,which means that there is no foreign protein in the antibody.

 

Methotrexate is usually given with Remicade to prevent the immune system from reacting to the antibody because of the mouse protein. DE27 is what is called a human monoclonal antibody. It's fully humanized,and there is no foreign protein.

 

Abbott Laboratories received U.S. Food and Drug Administration (FDA) approval this week to market adalimumab (Humira), previously known as D2E7. The drug was approved for the treatment of moderately to severely active rheumatoid arthritis (RA) in patients who have had insufficient response to one or more traditional disease-modifying antirheumatic drugs (DMARDs). Adalimumab is approved for use alone or in combination with traditional DMARDs.

"We're pleased to receive the approval of HUMIRA earlier than anticipated," said Miles D. White, chairman and chief executive officer, Abbott Laboratories. "The approval of HUMIRA is not only a milestone for Abbott, more importantly it is an example of the positive impact pharmaceutical innovation can have for people living with chronic and debilitating conditions like RA."

Adalimumab should be administered every other week by subcutaneous injection (the recommended dose for most patients is 40 mg). A specially designed prefilled syringe for RA patients whose hands may be affected by crippling joint destruction will be available in pharmacies next month. Abbott is confident it can supply sufficient quantities to meet patient demand and recently announced a manufacturing expansion to meet future demand for adalimumab, as well as for other biologics in its pipeline.

The approval of adalimumab was based on the efficacy and safety data obtained in four controlled clinical trials in more than 2,000 RA patients. The efficacy of adalimumab was assessed by evaluating patients' improvement in RA signs and symptoms response scores and the inhibition of radiological evidence of the progression of structural damage in RA. Safety was also assessed in these trials, including one of the largest safety trials of a tumor necrosis factor (TNF)-alpha antagonist.

In these trials, 14 (22%) of 63 patients experienced an improvement in RA signs and symptoms as early as one week. American College of Rheumatology (ACR) responses have been seen in some patients for up to three years.

"In my experience with Humira, some patients see a rapid improvement in their signs and symptoms as early as one week, which allows them to participate in normal daily activities," Michael Schiff, MD, director of clinical research at the Denver Arthritis Clinic, clinical professor of medicine in the Rheumatology Division of the University of Colorado School of Medicine, said in a news release from Abbott. "Just as important is the ability of Humira to inhibit the progression of the disease, which means it slows the damage to the joints that occurs over time." Dr. Schiff was a lead investigator for the drug's clinical trials.

Adalimumab is a monoclonal antibody that works by blocking TNF-alpha, a protein that plays a central role in the inflammatory responses of autoimmune diseases such as RA