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The initial evaluation of the patient with RA should document symptoms of active disease (i.e.,presence of joint pain,duration
of morning stiffness,degree of fatigue}, functional status,objective evidence of disease activity (i.e., synovitis,as assessed
by tender and swollen joint counts,and the ESR and CRP level) mechanical joint problems (i.e., loss of motion-joint instability,
malalignment, and/or deformity), the presence of extraarticular disease and the presence of radiographic damage. The presence
of comorbid conditions should be assessed. The patient's and physician's global assessment of disease activity and a quantitative
assessment of pain using a visual analog scale or other validated measure of function or quality of life are useful parameters
to follow during the course of the disease. This baseline information greatly facilitates assessment of these progression
and response to treatment.
Baseline laboratory evaluations should include a complete blood cell count (with white blood cell differential
and platelet counts),rheumatoid factor (RF) measurement,and measurement of ESR or CRP. Evaluation of renal and hepatic functions
is necessary, since many antirheumatic agents cause renal or heptic toxicity and may be contrainindicated if these organs
are impaired. Since the hands and feet are so frequently involved in RA,radiographs of these joints as well as other affected
joints establish a baseline for future assessment of structural damage. Arresting and preventing structural damge is the primary
goal of therapy,and radiographic studies of major involved joints may be needed periodically.
Selection of the treatment regimen requires an assessment of prognosis. Poor prognosis is suggested by older age at disease
onset,high titer of RF,elevted ESR,and swelling of >20 joints. Extraarticular manifestations of RA,such as rheumatoid nodules,Sjogren's
syndrome, episcleritis and scleritis,interstitial lung disease, pericardial involvement,systemic vasculitis and Felty's syndrome,may
also indicate a worse prognosis,but have not been widely adopted for clinical practise.
The ACR criteria for 20 % clinical improvement (the ACR 20 ) requires a 20 % improvement in 3 of the following parameters;patient's
global assessment,physician's globl assessment,patient's assessment of pain,degree of disability,and level of acute-phase
reactant. These criteria have been expanded to include criteria for 50 % and 70 % improvement measures (i.e.,ACR 50,ACR 70).
Other criteria,such as Paulus criteria,have bee employed. More recently,radiographic progression (e.g., the Sharp score )
has been utilized as an outcome measure Optimal management of RA involves more than pharmacologic
therapy. Early in the course of the disease the patient needs to know that polyarticular,RF positive have a 70 % probability
of developing joint damage or erosions within 2 years of onset of disease. Since studies have demonstrated that treatment
with DMARDs may alter the disease course in patients with recent-onset RA,particularily those with unfavourable prognostic
factors,aggressive treatment should be initiated as soon as the diagnosis has been established. At each followup
visit,the physician must assess whether the disease is active or inactive. Symptoms of inflammatory (as contrasted with mechanical
) joint disease,which includes prolonged morning stiffness, duration of fatigue and active synovitis on joint examination,and
active synovitis on joint examination,indicate active disease and accessitate consideration of changing the treatment program.
Occationally,findings of the joint examination alone may not adequately reflect disease activity and structural damage,therefore,periodic
measurement of the ESR or CRP level and functional status,as well as radiographic examinations of involved joints should be
performed. Functional status may be determined by questionnaires such as the Arthritis Impact Measurement Scale
or the Health Assessment Questionnaire.It is important to determine whether a decline in function is the result of inflammation,mechanical
damage,or both,treatment strategies will differ accordingly. The ACR has developed criteria for defining improvement and clinical
remission in RA. These criteria have become accepted for outcome assessment in clinical trials. The patient will
need to become involved in the process of making decisions about treatment. If treatment does not fully control the disease,the
patient may struggle emotionally as well as physically in adjusting to this chronic disease,it's flares,and the concomitant
loss of function. Rheumatologists,other physicians and their office staff should play important roles in educating the patient
and the patient's family about the disease and providing longitudal supportive care.Other health professionals, familiar with
RA,including nurses,physical therapists, occupational therapists,social workers,health educators, health psychologists and
orthopedic surgeons,may be involved in interdisciplinary team approach in the comprehensive management of RA. Instruction
in joint protection,conservation of energy,and a home program of joint range of motion and strengthening exercises are important
and essential in achieving treatment goal of maintaining joint function. Physical therapy and occupational therapy should
help the patient who is compromised in activities of daily living. Regular participation in dynamic and even certain selected,suitable
aerobic conditioning exercise programs improve joint mobility,muscle strength,aerobic fitness and function and psychological
well being without increasing fatigue or joint symptoms.
The initial evaluation of the patient with RA should document symptoms of active disease (i.e.,presence of joint pain,duration
of morning stiffness,degree of fatigue},functional status,objective evidence of disease activity (i.e., synovitis,as assessed
by tender and swollen joint counts,and the ESR and CRP level) mechanical joint problems (i.e., loss of motion-joint instability,
malalignment,and/or deformity), the presence of extraarticular disease and the presence of radiographic damage. The presence
of comorbid conditions should be assessed. The patient's and physician's global assessment of disease activity and a quantitative
assessment of pain using a visual analog scale or other validated measure of funcion or quality of life are useful parameters
to follow during the course of the disease. This baseline information greatly facilitates assessment of these progression
and response to treatment. Baseline laboratory evaluations should include a complete blood cell count (with white blood cell
differential and platelet counts), rheumatoid factor (RF) measurement,and measurement of ESR or CRP. Evaluation of renal and
hepatic functions is necessary,since many antirheumatic agents cause renal or heptic toxicity and may be contrain -indicated
if these organs are impaired.
Since the hands and feet are so frequently involved in RA,radiographs of these joints as well as other affected joints
establish a baseline for future assessment of structural damage. Arresting and preventing structural damge is the primary
goal of therapy.and radiographic studies of major involved joints may be needed periodically. Selection of the treatment regimen
requires an assessment of prognosis. Poor prognosis is suggested by earlier age at disease onset,high titer of RF,elevted
ESR,and swelling of >20 joints. Extraarticular manifestations of RA,such as rheumatoid nodules, Sjogren's syndrome,episcleritis
and scleritis,interstitial lung disease,pericardial involvement,systemic vasculitis and Felty's syndrome,may also indicate
a worse prognosis,but have not been widely adopted for clinical practise.
The ACR criteria for 20 % clinical
improvement (the ACR 20 ) requires a 20 % improvement in 3 of the following parameters;patient's global assessment,physician's
globl assessment,patient's assessment of pain,degree of disability,and level of acute-phase reactant. These criteria have
been expanded to include criteria for 50 % and 70 % improvement measures (i.e.,ACR 50,ACR 70). Other criteria,such as Paulus
criteria,have bee employed. More recently,radiographic progression (e.g., the Sharp score ) has been utilized as an outcome
measure.
When rheumatologists in this country were surveyed in 1999, 47% of them viewed combination DMARDs as
appropriate initial therapy, and 46% of that group had used combination DMARDs for more than 30% of their patients. Aggressive
therapy, usually in combination, may be appropriate for some patients. That is counter-balanced by a second survey of Canadian
and US rheumatologists in 1996, where there was some preference expressed for a single agent, if possible, in the treatment
of rheumatoid arthritis.
With our new drugs, we have changed our vocabulary and our goals when we think of treatment for rheumatoid arthritis.
Our goals are: no constitutional symptoms, returning to work, minimizing the impact of this disease on daily living, and changing
the course of disease progression. We have made our biggest leap in the last several years with discussion about slowing,
stopping, and perhaps even reversing this previously relentless chronic disease. Ideally, you would like a drug that is effective
not just for symptoms, but one that inhibits disease progression, has that efficacy sustained over long periods of time, and
is safe and well tolerated with minimal monitoring required. We would like that to be simple, perhaps monotherapy.
Rheumatologists are moving from that first treatment paradigm to this. Our current approach still may be initial treatment
with traditional DMARDs, but then quickly adding drugs, including a biologic agent. That evolution emphasizes early aggressive
treatment, biologics, monotherapy if possible, or combinations for non- or partial responders, and the potential to reduce
or discontinue our previous drug. What is the paradigm change in terms of therapy for rheumatoid arthritis? In the last few
years, we understand the severity and the nature of rheumatoid arthritis more than we ever have. What are those paradigm shifts?
(1) we're using disease modifying antirheumatic drugs (DMARDs) earlier; (2) we're using aggressive methotrexate therapy; (3)
we're using combination therapy; and (4) we're using biologics.
In terms of early DMARD use, there are 2 issues that most physicians want to address. If I use a DMARD early, will it
make a long-term difference to my patients? And, if I use a DMARD early, will I have a better clinical response? The concept
that initiating a DMARD early may have a longer-term benefit on the patient. Are there any data to support that? There are
at least 2 studies to suggest it. The first is a study by Lard. He took a group of patients who, within 2 weeks after presenting
with their diagnosis, were started on a DMARD. He took another group of patients and waited a mean of 4 months and then started
a DMARD. The delay, on average, is about 4 months. These populations weren't exactly matched, but they were pretty closely
matched. If you look at the radiological outcome, the Sharp score, those patients who were treated early had a reasonable
reduction in Sharp score, whereas those patients who were only 4 months delayed on average had quite a significant increase
in Sharp score over time. That suggests earlier treatment will have a long-term benefit.
The second study has to do with disability outcomes. This study by comes out of British Columbia. They did a hydroxychloroquine
(Plaquenil) trial. They did a 9-month, double-blind, placebo-controlled trial. At the end of 9 months, they put the placebo
patients on Plaquenil. They watched the patients who got Plaquenil at the beginning of the study, and watched those patients
receiving Plaquenil 9 months later, ie a delay, to see whether, long term, there would be a difference. If you look at improvement
in those patients who got Plaquenil at the beginning, in terms of disability, there is a 57, 58, and 60 in standard deviation
units. The patient population that started 9 months later, out to 33 months later, didn't match their counterparts. They still
had more disability after 3 to 4 years and were not up to the base of those individuals who started on Plaquenil initially.
Aggressive, early therapy could make a long-term difference. We've seen it radiologically and in terms of clinical outcomes.
What about methotrexate? What about better response to DMARDs in early versus late disease? If I use a DMARD early, will
I have a better response than late? There are not a lot of data to support that. I'm going to give you 2 pieces of data that
are certainly suggestive, but not definitive. One of these pieces of data comes from the trials with etanercept. They looked
at the Stanford Health Assessment Questionnaire (HAQ) outcomes, the disability outcomes, in patients in the Moreland trial,
which was monotherapy late disease, an average of about 10 to 12 years of disease, versus the outcomes in the Early Rheumatoid
Arthritis (ERA) trial in patients who were treated with under 3 years of disease. Other than disease activity, for the baseline
outcomes of tender joints, swollen joints, etc, they were comparable. Investigators had 2 comparable populations, 1 early,
1 late, and they asked the question: Using the same dose of etanercept, do you have a better response? These data show, in
the ERA trial, there was a difference between these 2 populations, a better improvement in HAQ if you treated early.
The second study is a meta-analysis. This is a study by Anderson. It's probably the only study done in terms of asking
the question, "Earlier treatment, better response?" This is published in Arthritis and Rheumatism. There were various DMARDs
used. They looked at Plaquenil, azathioprine (Imuran), and methotrexate. They even looked at Prosorba (protein A-based extracorporeal
immunoadsorption, silica). The concept is, if you treat people with a short disease duration, regardless of their treatments,
in general, your sedimentation rate is improved, your swollen joint count is improved, and your tender joint count is improved.
This is the proportion of those people who are improving by at least 20%. If you treat them late, if they're treated at 5
to 10 years, there is a significant difference. Suggestive, but not definitive, data indicate if you treat earlier, you're
more likely to have a response.
What about aggressive methotrexate dosing? Are there any data to say that higher doses of methotrexate make a difference
versus lower doses? Dan Furst did a study. He asked the question whether 20 mg of methotrexate over 14 weeks is any better
than 10 mg over 14 weeks. Here is the percentage of patients with American College of Rheumatology (ACR) 50 and with improvement
of at least 50%. The 20-mg dose improved more at tender joint count, swollen joint count, global joint count, and activities
of daily living (ADLs) relative to 10 mg. These data say higher doses work better than lower doses, that 20 mg is better than
10 mg. The median dose of methotrexate used about 3 years ago, when they did a pharmaceutical survey in the United States,
was 11 mg. Another study that suggests the possibility that methotrexate works well is the Early Rheumatoid Arthritis trial.
We think about etanercept as one of the gold standards
Can we take methotrexate, which is our gold standard, raise the dose in 2 months to 20 mg, and compete with etanercept?
In the first 4 months, you don't compete. To an extent, etanercept worked quicker. By 12 months, the 2 look almost identical.
There is only a 5% difference between etanercept and methotrexate in terms of clinical outcomes at 1 year. These are very
good outcomes. Most of the other disease modifiers and biologics aren't going to beat methotrexate. So why use it? Or, why
not use it? Here is the concept. Radiologically, at 2 years, there was a minor difference between etanercept and methotrexate.
The Sharp score point differences were about 2. However, it's clear that, over time, radiological outcomes are linear. It
was thought to be only 6 years, but now we're talking 15 to 20 years. The concept is, if these 2 curves continue to diverge,
by 5 years, there is going to be a 5 Sharp score point difference and at least that from then on.
How long does it take to notice a difference, radiologically, in terms of change in Sharp score? Nobody knows, but I'll
give you a number anyway. About a 50 Sharp score point difference and your grandmother can tell the difference between those
2 x-rays. Therefore, if it's 5 years, it doesn't take very long for those 2 x-rays to be different. If you continue methotrexate,
you will have different x-rays than if you were on etanercept. Over time, the tolerability isn't as good with methotrexate,
so that 74% of the patients stay on etanercept for 24 months, and 59% of the patients stay on methotrexate. There is a difference
between the two. Methotrexate makes some people feel sick. Etanercept makes them feel good. If the cost would come down, everybody
would be switching to etanercept.
What about combination therapy? There are 3 ways to combine DMARDs. You can add a DMARD in those partially responsive.
That's called step up. We can use them in parallel from the beginning, or we can use step down. We can use multiple DMARDs
at the beginning and, as the patient responds, keep removing DMARDs until you're back down to baseline, maybe with monotherapy.
That's the induction and maintenance concept. You've seen lots of add-on therapies, because that's the way the trials are
being designed. The step-up therapy here is leflunomide. In patients who are partially responsive to methotrexate, the combination
is a 51 ACR 20 compared with methotrexate alone, which means you continue on it. There is quite a difference. There appears
to be a clinical added benefit to adding leflunomide in patients who are partially responsive to methotrexate. These are some
data that suggest combination therapy is not bad.
Two studies recently asked the following question: At the beginning, if I initiate methotrexate and sulfasalazine, will
it be better than either alone? Two studies say no. Initiating sulfasalazine and methotrexate at the same time is not better
than either methotrexate or sulfasalazine alone. These are data using the Disease Activity Score (DAS) and the ACR 20
scores. What about triple therapy? Jim Ardell added triple therapy at the beginning and asked whether it was better than Plaquenil,
sulfasalazine, or methotrexate alone. He had striking results. The triple therapy at the beginning was much better than the
others. There were a couple of problems with the study. It was pretty long. There were long-duration patients, about 10 years.
The number of patients who were methotrexate naïve was quite considerable, and most of the patients failed about .9 DMARDs.
It's an unusual population, but these studies were done a number of years ago when methotrexate wasn't on everybody's
"radar screen." It's still an unusual population. This study is critical to be reproduced in early rheumatoid arthritis because
it says that the toxicity wasn't any different whether you were on triple, double, or single therapy. There are a couple of
open-label trials. There is a triple therapy trial -- methotrexate, sulfasalazine, and Plaquenil versus methotrexate and sulfasalazine,
or methotrexate and Plaquenil. It was triple therapy versus double therapy versus single therapy. The single therapy was methotrexate.
They showed triple therapy worked quite well. The problem in this study is they used methotrexate at low doses up to 15 mg.
I don't know that triple therapy is better than high-dose methotrexate. I don't think we'll ever see the study.
This is another trial. In this trial they used combination therapy along with corticosteroids versus corticosteroids
and sulfasalazine. It was actually quadruple therapy versus sulfasalazine, plus or minus cortisone. You didn't have to add
cortisone. The results were very good. The combination therapy was excellent. The problem is their comparator was sulfasalazine
and I'm not sure this combination is any better than high-dose methotrexate.
There is step-down. The key trial for step-down was the COBRA trial (comparison of combined step-down prednisolone, methotrexate
and sulfasalazine with sulfasalazine alone in early rheumatoid arthritis). It was high-dose steroids for a short period of
time and then eventually tapered off. They used a methotrexate combination, and a sulfasalazine combination. All triple therapy
was compared with sulfasalazine alone. Notice the clinical results. Patients on triple therapy did extremely well until you
stopped the prednisone. Then they came back to the baseline. They came back to what sulfasalazine alone looked like. After
you dropped the steroids, they looked clinically alike.
The only difference was a significant difference in the radiologic outcomes when you added low-dose methotrexate
along with sulfasalazine, and the prednisone versus sulfasalazine alone. This is triple therapy slowing progression relative
to sulfasalazine. At 1 year, the patients on sulfasalazine were allowed to go onto any therapy they wanted. Over the
next 5 years, those patients on sulfasalazine never caught up. That may have to do with the DMARDs they went on, but the sulfasalazine
group never caught up to the triple-therapy group. At this point, remember, you're only on sulfasalazine. You've already stopped
the prednisone and the methotrexate. It's an interesting concept that with early aggressive therapy, tapering off "the bad
guys," and leaving a simple drug on, you may end up with a significant difference radiologically.
Biologic therapy says that if you fail methotrexate and you add a disease modifier, like a biologic, you have good data.
There are good ACR 20s and 50s in combination: etanercept versus methotrexate. With infliximab you have to use methotrexate,
good data. Anakinra (Kineret) just came on the market recently. What you see, again, are reasonable data. These time courses
are a little different. You can't compare study with study but, in general, it says if doctors add a biologic to those patients
partially responsive to methotrexate, they have additional clinical benefit. This is not a positively established fact.
In these trials, you never had the biologic arm alone. You had the methotrexate arm. You had the combination arm. But,
you never had the biologic arm. How do doctors know that you really need methotrexate? There is an uncanny concept with the
ACR 20 outcomes. If you used etanercept as monotherapy, the ACR 20 was 60. If you used it and added methotrexate, the ACR
20 outcome was 71, not very different.
Leflunomide as monotherapy, the ACR 20 outcome was 46. In those patients who were partially responsive to methotrexate,
it was 46. If you look at anakinra (Kineret), it was 38 by monotherapy, and adding methotrexate, it was 37. You've got
to wonder whether you really needed the methotrexate if those numbers look alike. Those are the data. It's food for thought.
What's new? Scientists have made great gains in terms of the clinical and radiological outcomes with tumor necrosis factor
(TNF) antagonists. The new agent to come out in terms of TNF-Humira (Adalimumab). This is a fully human anti-TNF monoclonal
antibody with a half-life of about 2 weeks. It fixes complement. It's able to use cells,like infliximab. It kills those
cells that actually make TNF. It was given subcutaneously once a week as monotherapy. The results were quite good. The ACR
20s were comparable to anything else we've seen, around 55%. The ACR 20s were about 25% or 30%. That is good. This is once-weekly
subcutaneous administration in a severe population of patients.
What happens if I have a partial response patient population on methotrexate? Using an average dose of about 16.8 mg,
patient disease duration was 12.3 years. What happens when you add subcutaneous Humira (DE 27-formerly )every second
week in those patients who were partially responsive? ACR 20 is about 65%. Reasonable. ACR 50 at the 40-mg dose was quite
high at 53%, and ACR 20 was 26.9%. This value was higher than we see in most studies, but the 80-mg dose was slightly less,
in terms of efficacy, than the 40-mg for reasons that are unclear. This study was not powered to tell the difference between
doses, so we still don't know what the minimally effective dose is. At least we can say there is good benefit if you give
subcutaneous D2E7 every second week.
Cortisone is such an important drug that we have, but it needs to be used very carefully because it can cause a lot of
problems. Using intermittent injections of cortisone into the joints can be a real godsend and can really improve people's
function. For example, if someone's shoulder is limited in its ability to move, an injection of cortisone in the shoulder
can provide rapid relief that can really provide benefits while you're waiting for the disease modifying drugs to take effect.
Gold is an old treatment, and in some ways that's really nice because physicians know a lot about it. They know
what's good about it, and the bad about it. It is an effective treatment in about 55 percent of people who use gold. Gold
suppresses the disease partially, but it's very slow. You need to use it with weekly injections for 20 weeks often to see
clinical benefit. And sometimes people can have problems with rash or low blood counts. Others can have oral sores or
even problems with protein or blood leaking from the kidneys. While gold can be used safely and there may be particular patients
that's a really good drug to use, it is something that is sometimes a troublesome drug, too. One of the problems with
gold is that patients and doctors do have to wait often the 20 weeks or more to make a decision whether this is an appropriate
therapy, and also,may have lost six months of ability to treat the patients. Gold is probably not a very good first choice
of a second-line agent or of a disease modifying drug unless there's some reason that the physician didn't want to use methotrexate.
Patients has to get a urine test and a blood test once a week to be sure that they don't have the kidney and bone marrow troubles
that some patients have.
Methotrexate is actually a therapy that's been around for a very long time. It was
used for cancer patients, and it's been used in rheumatoid arthritis for well over 20 years now. The way it actually works
is still not perfectly clear. Physicians know it works by decreasing inflammation, but it also works by decreasing immune
cells. A very large study that was published in 1999 showed that, finally, that it is not only a medicine that makes
the patients' signs and symptoms or their joint pain and swelling better, but it slows the x-ray progression down, so it truly
is one of our medicines that modifies the disease. With reference to side effects,it's important also to understand that there
are risks with not treating rheumatoid arthritis,that's the perspective or the frame in which you've got to look at the possible
risks of methotrexate.
Methotrexate is very well tolerated by most people, and even in relatively high doses, more
than 85 percent of people will be able to continue it for at least a year. The other signs of its safety is that at five years,
more people tend to stay on methotrexate than any other drug. It's important to note that generally it is very well tolerated
by most people. There are two types of side effects. One is the relatively common kind of minor side effects. Occasionally
people are a little tired or may have a little bit of nauseousness or loose stools after they take their weekly dose. And
then there are probably the less common or more sporadic type of problems which can be more serious, which are methotrexate-associated
serious liver scarring, which occurs approximately in one in 1000 people who take it for five years, or serious lung scarring
which can occur in around one and a half or two percent of people. Methotrexate can be administered either by pill, which
is the most common way that it's used in the United States, but it also can be administered by injection. The injections offer
possibly a little more safety, a little more regulation of the dose, and in higher doses doctor's are able to have to switch
their patients to injectable methotrexate.
Leflunomide ( Arava ) is a drug which is similar in some ways to methotrexate
in that it impairs the ability of inflammatory cells to reproduce rapidly. It is a bit expensive, about 280 dollars a month,
and so that's actually somewhat of a barrier to people who don't have health insurance, but it is generally well tolerated
by people. The side effect seen most commonly is loose stools associated with it, but for most people that's not too much
of a problem. It has some benefits in that it does seem to have some benefit within the first six to eight weeks of use, and
it appears that its ability to suppress swelling and pain and to prevent joint damage is perhaps close to or similar to methotrexate.
It would be an alternative to patients who either did not respond or could not take methotrexate.
Plaquenil
has been used for a long time, and there are some really nice features about it which doctors include that it really doesn't
need frequent blood monitoring, and it does not have a significant toxicity to liver. However, at least in patients with recent-onset
rheumatoid arthritis, there has never been a published study that has shown that it slows or prevents joint damage. Therefore,for
someone who has significant and functionally limiting rheumatoid arthritis, Plaquenil is not a good first choice. And also
I think the fact that it does take many months to see a response, we may lose our window of opportunity.
In
Europe and outside of the United States, sulfasalazine is very commonly used. It's less commonly used in the United States.
Sulfasalazine can be a very helpful drug. It is relatively inexpensive. The mode of onset is not as fast as methotrexate,
but certainly faster than gold. The side effect profile, unless it causes stomach upset, is generally pretty good. In the
research studied, it may not be as effective as methotrexate or leflunomide, but it is certainly an effective treatment. For
some people, it is a very useful drug. In people with the most severe arthritis, though, again that a faster-acting and more
potent drug would be a choice of physicians.
D-Penicillamine, is rarely used now,especially with the newer drugs
available. With the advent of the biologics, doctors don't need to use it because it is a troublesome medicine. Now that we
have a number of better-tolerated, faster and more effective treatments, these are clearly treatments physicians don't use
as often.
Azathioprine is a drug that is effective to some degree in reducing joint swelling and pain. The data
supporting the idea that it prevents joint damage is really not as robust, and it's really quite slow. It's largely been supplanted
in its place by Arava.
Treatment with cyclophosphamide was tested in the '60s, late '60s, early '70s, and it's
certainly a very potent agent, but unfortunately it does carry with it a substantial risk of developing leukemia in the ten
years after being treated with it. Cyclophosphamide really is not,or rarily used for rheumatoid arthritis.
Summary:
In someone who has either very mild rheumatoid arthritis or maybe you're not sure it's rheumatoid, rheumatologists might consider
Plaquenil early, but choices such as sulfasalazine, Arava or methotrexate would be their first choices.
Biologics: Enbrel, which is etanercept, and infliximab, the trade name is Remicade. They both are targeted towards the
inflammatory messenger called TNF or tumor necrosis factor, and these are similar in many ways. Enbrel is actually the
receptor that TNF binds to on the inflammatory cell, and research-scietists figured out how to make that little receptor and
how to help it circulate in the blood, and so what it acts as a sponge to take this out of circulation. Infliximab
or Remicade is a little different in that instead of just a receptor floating around, infliximab is an antibody, and that
is it binds specifically to TNF and "kills" or eliminates it out of the blood. With Enbrel individuals can
administer that to themselves, and so that gives them a measure of control and independence. It's also not really associated
with a meaningful immune response, so it can be taken all by itself. Remicade is a little different in that it needs
to be given as an intravenous treatment, and because one third of Remicade comes from a mouse, they have to take a drug like
methotrexate with it to suppress making anti-mouse antibodies Currently,these drugs are limited because of cost
and the requirements are that patients if they fail on an initial agent such as methotrexate need to be considered for a biologic,unless
one has private health coverage and most plans have the same limitations. Infliximab or Remicade, because of the mouse protein
in it, one has to continue the methotrexate whereas with Enbrel or etanercept, it can be used as a single agent with very
good success. The other important point is that not all of these medicines work for every patient, and rheumatologists
have to make decisions which are go, no-go decisions whether this is the right medicine and the right dose of medicine for
the patient. Being on one of these medications is not enough. The rheumatologist and the physician taking care of the patient
has to make a decision whether it's really doing the job that it needs to be done. Therefore,rheumatologists will look at
the patient's joints and they'll do a joint count so they find out how many of the joints are tender and how many are swollen,
and they will follow x-rays on a periodic basis to be sure that there is no damage that's progressing to make decisions whether
or not this is an effective medicine, whether it be a biologic such as Enbrel or a synthetic such as methotrexate. One
of the things that we as a society have to come to grips with is that the cost of biologics is much more than methotrexate
is. And so, while there are individuals that without any question should be started on the biologics first, like people with
significant liver disease or someone who has moderately severe kidney disease, in most individuals who do not have those processes,
probably an initial trial of a potent disease-modifying pharmaceutical like methotrexate is probably from a financial standpoint
the most sensible thing, and probably from a society stand. . The actual cost of the biologics is higher than methotrexate.
Also, many of the patients with rheumatoid arthritis often come already on methotrexate. Many internal medicine doctors have
already started them on methotrexate, and a decision needs to be made is that the right medicine and if so, is it the right
dose, and often it's too low, and one pushes the dose. A comparative study has been shown that higher doses of methotrexate
work better. This is a very individual decision with the patient and the physician. But what doctors would focus
the most on isn't necessary what is the first drug that is used but that these biologics are not something that should be
saved until there are no other options. These are drugs that should be used easily in the first six months to a year of disease
if traditional therapies don't very effectively suppress the arthritis. People should not wait because, the pace and
the progression of joint damage is a continuous and rapid process, and if we can in a rapid fashion suppress people's disease,and
over many years will reduce the amount of joint damage which should translate into better work, better health, and better
social function. We're all self-managers, and there are two ways of looking at that. If you choose to be a self-manager
and you make a deliberate choice and create a mindset that you will take control of the management of your disease, you will
likely turn into being a good manager. Most individuals use one to three coping skills, and sometimes denial is that coping
skill, but if you deny that you have disease, that is a rather poor thing because you are still a self-manager, you're just
a poor self-manager, and you're not making interventions that can help you and your health over time. Overcoming the
grief and the feelings of loss, and accept that "Yes, I have this probably incurable disease," but quickly coming around to
the idea that, "Well, I'm going to do whatever it takes so I can live as full life as I can and that this is more of an inconvenience
to me rather than a life-changing illness." ----Acceptance. Don't endanger your health or waste your time and money on "cures".
See a rheumatologist and have him or her treat your disease.
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| Click Picture: RA Essentials I |
RA Essentials II
Socks Rheumatoid Arthritis Links
*All my sites.--I have written many articles over the years.*Disregard any reference to "Vioxx" which was taken off the
market by the FDA a few years ago. The NSAID had proven to have negative adverse heart problems to many patients--rise in
blood pressure.
All of my RA Geocities links will be unavailable for future view.
Gold therapy is outdated.
After 8/1/09 - Future editing will be unavailable- This site is intended for RA patients.I recieve no remuniration.
I will have to pay for editing the site.
Re clicking links:Socks Rheumatoid Arthritis Page 1 and Socks Toxicity And Drugs In RA were the first sites built at
another web site (I vil) and later transferred to Tripod. If a link does not connect- i.e-I vil-.go to the main site----Socks
Rheumatoid Arthritis Links. I cannot access the old links because I forgot the old password.
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