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Sock's Toxicity And Drugs In RA:
Summary
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In 1996,the ACR wrote a new set of guidelines for the management of RA. The recommendations underline that all people  "whose RA remains active despite adequate treatment with NSAIDs are candidates for DMARDs therapy".
 
 They recommend that the use of DMARDs not be delayed beyond three months. They point out that people who have active RA marked by pain and swelling in mutiple joints and who have rheumatoid factor in their blood stand a greater than 70 % chance of developing joint damage or bone erosions within 2 years of the begining of the disease
 
That is why current treatment of RA tends to feature early,aggressive treatment,which means the use of DMARDs, often in conjunction with NSAIDs. According to the guidlines,"the goal of treatment is to intervene in the disease before joints are damaged."
 
A series of research studies in the 1990s have given us new insights into how MTX works. One of the pathways that it blocks results in the release of an anti-inflammatory chemical from cells that have taken in the MTX. This chemical fits right into the picture of inflammation as we understand it,because it plugs up receptors on cells in inflamed joints and slows the activity of those infamous inflmmatory chemicals,TNF-alpha and IL-1. ( MTX is not classified as a prime inhibitor of TNF-alpha,or IL-1.)
 
When MTX is used for cancer,at far higher doses than are given for RA,there is a halt in the production of DNA, resulting in the death of cells,expecially in the rapidly dividing cells of cancerous tumors. Remember,it is only in 1999 that MTX was shown in clinical trials that it is indeed,a disease modifying drug ( slows x-ray damage ). And trials were done on subcutaneous injection efficacy tests,at the higher dose used in RA in the later part of  1998-99.
 
Now physicians usually prescribe the newer hydroxychloroquine sulfate (Plaquenil) for people with early,less aggressive,mild to moderate RA,who usually lack the rheumatoid factor in the blood (in the majority of cases.) If some relief is symptoms is not shown within six months,its use is usually discontinued.
 
There is some scientific explanations on how this medication works,-this drug may make the internal contents of cells more alkaline,and retard the release of certain cytokines,but what ever how it works,or if it does,the effectiveness of this medication in a relatively small group of people underlines again the variable nature of the disease process. What works for some will not work for others. It has low toxicity.
 
Like Plaquenil,sulfasalazine is usually prescribed in milder cases of RA. It shows some positive effects after up to three months in over 30 % of people Despite its intended use as an antibacterial,there is no good evidence that this is the mode of action,and the reason for the effectiveness of sulfasalazine has yet to be determined.
 
Gold was originally used a high doses with many side effects. In the 1940s doses were lowered and when studies showed less side effects at the lower doses,gold was used more ofte, Gold takes longer to show its effects. About 60 % experienced a reductin in pain and inflammation. It was thought that gold had the possibility of remission,but it was not proven in trials. gold ,even at the current doses has many possible side effects. It's popularity is diminishing. Oral gold auranofin,is slow acting and less efficacious than the injectable form.
 
There are few clues as to how gold works. The gold is taken up and concentraed in cells lining the joints,and by the macrophages,those cells that help to sustain RA in many ways-including making rhe inflammatory chemicls TNF-alpha and IL-1.
 
Understanding these kinds of details is more than just academic interest to scientist and pharmacutical companies. It can lead to the creation of less toxic.or non-toxic RA medications,that are aimed or targeted at precise receptor sites

The newest approach to RA treatment is one in which combinations of DMARDs are used in the early stages of the disease. There is an world-wide ongoing interchange of ideas within the worldwide rheumatology community about how best to to translate"early diagnosis and early ,aggressive treatment with DMARDs".
 
What are the optimal combinations of drugs to use for a particular person ? What signs and symptoms indicate that a specific combintions of drugs to use for a particular individual ? What signs and symptoms indicate that a specific combinations might be better than another ? What is the best way to diagnose RA early,and to predict which people are more likely to develop persistent and more serious damage ? Whe is it better to add DMARD,one after the other as they become inefficective,or is it better to use combinations of DMARDs right away,including steriods ? What is the most accurate way to monitor disease activity and assess damage ?
 
Newer,more sensitive methods of looking into joints,such as ultrasound, magnetic  resonance imaging (MRI),and machines that measure bone mineral density are under investigation.
 
With all the advances in RA,treatment is still partially dependendant on certain amount of "educated,investigated-trials-errors" and a lot may still depend on the experience that the medical practisioner has accumalated through specilized training,and upgrade of that knowledge. An "educated-guess' is one of tools used in RA treatment.
 
 
One of the important questions always asked about a RA medication is whether or not people taking it will continue to respond favorably to it over an extended period of time. People can become refractory (non-respondent) to a medication,i.e., even though they continue to take it,the drug becomes less effective.
 
Rheumatologists are regarding the biologics (5 year reports is favourable-Enbrel) and other intriguing TNF-alpha blockers with caution,but with optimism. As more experience is gained with their use,and as other forms of cytokine antagonists become available,this novel approach will more than likely become an integral part of treatment programs aimed at gaining control over RA. Current costs prevent wide spread use to all RA patients.but in many cases conventional medicine have proven
 

Facts of life:
 
No matter how concientious your physician is,the time limit does not permit your physician to go over all the important details that a new and even older patient is entitled to. In order to preserve time some important tests may not be done.
 
One of my pharmacist friends said about 4 years ago: "You need only take one pill and your arthritis will be controlled". I wondered what it was so I asked him the name of the wonder drug. He replied that he wasn't sure of the name but a well knowen local g.p. had said ,"It is the ultimate for arthritis patients". I thought,"Why doesn't my rheumatologist know about it if was so revolutionary. The product was Celebrex (NSAID).-it was about the time period when it was first introduced.
 
In 1999 when Arava was introduced I heard a different ,but similar story. When the biologics were first introduced,I spent hours on research and joined pro-active organizations and fought for it's availability to all patients. At that time my disease,RA was like a "raging blast furnace." I came across a fellow patient who was fortunate to got on early clinical trials funded by the manufacturer. She said,"I tried all the convential DMARDs and nothing worked for me,except the biologic-you should get on it."
 
Yes,indeed,why can not everyone with rheumatoid arthritis get it, if it was the ultimate. I spent hours sending e mails to provincial and federal departments that were responsible for funding health care. I was angry-it seemed so unfair.I even ws mad at the doctors,whose only interest was helping me with this disease,RA.
 
The patient ,I learned later,was a 25 year old female patient with  many friends working in health care with many important connections. She,I later learned-was on 7.5 mg methotrexate,but she was not tolerant to mtx therapy(according to her)  That part is agreeable to me,since 40 % of patients do not respond to mtx therapy. What bothered me was that at arthritis patient gatherings,she would go on the "soap-box" and say biological therapy was the ultimate. "It is the ONLY therapy for RA" I can just imagine what other patients suffering,more than her felt. "I know how I felt".
 
Actually,she had early mild RA,and the clinical trials,at that time was geared towards new patients. By the way,today she is on methotrexate. What is this story about trying all DMARDs ? Her application was rejected by the "special-access board" to continue biologics. Today she is very quiet. She can help by explaining her "true" story.
 
 I want to acknowledge that biological therapy is wonderful for those patients that who do not respond to conventional therapy, It is another option,as is Leflunomide-to those patients who do not respond to mtx It was only a few years ago that methotrexate,subcutaneous injection-25 mg was introduced and proved efficacious  . MTX has a long term history-doctors know it's problems and it's short-comings.efficacious through clinical trials
 
Biologic such as Enbrel have good 5 year results,but long term-what is the final result on controlling patient disease ? IT looks encouraging,and I only hope for the best. I am not mad any more as conventional therapy has,finally controlled my disease. Biologics react quicker with lesser side effects,but the cost ?? Does it warrent it for the majority ?
 
Everyone talks about ACR 20's 50's and 70's or whatever,and it's a guideline used effectively for patient efficaciousness at clinical trials,but in a recent clinical trial,that first year trial on Enbrel,e.g., was more efficacious for patients with early Ra,but when you look at the longer term,data,The percentage point differences is not that great to do cart-whels. Sure the manufacturers say they have done small trials with late RA patients too,with encouraging results.
 
In conclusion to those patients who feel "cheated" don't be. Biologics are wonderful for patients who do not respond to conventional medication,so is Arava,but again we are all different and we react differently to drugs. Change,only,when a particular therapy is not working for you,be it biologic or conventional therapy.
 
Conventional therapy certainly is not "thing of the past".--My personal history will "back-up" that statement.  Sometimes,listening to stories is not what it  is made up to be. Investigate and do research on your own,you'll be plesantly surprized wnen you get the true-full story. It is your body not others.--Mild,moderate and severe may make "Day and Night" differences in prognosis, diagnosis effects,and treatment.--This fact is repeated and repeated,but it is a fact. Early diagnosis and treatment with DMARDs whether it be biologics or conventional is the "key to unlocking the door to heart-break." Many patients do not recognize the basics or they don't want to acknowledge the facts.

 
Just because a medication has been approved by the FDA or Health Canada does not mean your health plan will cover it. Many managed care plans and government programs have formularies,a list of drugs they will cover. If the your medication is not on the formulary,it may not be covered.
 
Your health insurance company may require that you meet certain conditions before the drug is paid for. Sometimes you may have to try a cheaper medication or fail on it before you can receive a more expensive one.
 
Some insurance health plans require that you make a co-payment for drugs,and the co-payment may be higher if the drug is not in the company's formulary.
 
Your health insurance plan may have an annual limit on the amount it will reimburse you for drug costs. Look at your plan.
 
Exact terms of your coverage may change from year to year,so read your current policy carefully and call a representive if you don't understand something.
 
Medicare generally does not pay for prescription drugs in the U.S. Some people on medicare purchase supplemental policies to cover their prescription ( although co-pays and annual limits may apply)' Medicaid benefits are determined by state,but generally medicaid will pay for prescription medications on its approved formulary.
 
In Canada prescription drugs are covered by the different health programs. When it comes to biologic drugs it's a different story. Only 3 provinces cover biologic therapy. In most provinces,biologics are covered only,when a patient has not responded to conventional therapy,but be warned, its still a mixed state. There is a "special access plan" in Ontario,for example,when conventional therapy does not help,but even then,some patients are accepted,some are not,but recent,proposed, and more then likely,health reforms may hopefully change this,both in the U.S. and Canada.