Management Of RA:
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
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.
Although there is little difference in NSAIDs pharmacologically,individual NSAIDs
will show signiificant difference in efficacy and side effects in different individuals. NSAIDs,DMARDs and Steriods are covered
in other articles , therefore,we give give some updates and a review.
Patients with RA are nearly twice as likely as patients with osteoarthritis from NSAID treatment Risk factors for the
development of NSAID-associated gastroduodenal ulcers include advanced age ( 75 years and older ),history of ulcer,cocomitant
use of corticosteriods or anticoagulants,higher doseage of NSAID,use of mutiple NSAIDs,or a serious underlying disease.
The following approaches may be considered for patients with RA who would benefit from an NSAID but who are are at increased
risk of serious adverse GI effects: use of low-dose predisone instead of a NSAID,use of which are effective in decreasing
NSAID-associated gastroduodenal ulceration,include high dose H2 blockers,proton-pump inhibitors and oral prostaglanden analogs
While symptoms of dyspepsia are often improved by treatment with H2 blockers,one study showed that asymptomatic patients
with RA who were receiving both NSAIDs and low-dose H2 blockers were at higher risk of GI complications than those receiving
NSAIDs alone. Therefore,routine use of H2 blockers to prevent dypepsia or to protect against NSAID-induced gastropathy is
In two recent large trials comparing highly selective COX-2 agents with traditional NSAIDs,the patients in the selective
COX-2 agent group had significantly fewer GI events. There are several caveats,however.
If anticipated therapy is indicated (e.g.,as risk reduction for cardiovascular disease),an agent such as a nonacctylated
salicylate,use of a highly selective COX-2 inhibitor,or use of an combination of an NSAID and a gastroprotective agent.
Gastroprotective agents,addition of low-dose aspirin may partially ameliorate the benefit of less GI toxicity associated
with highly selective COX-2 agents. Morever,the use of a highly selective COX-2 agent has been reported to be associated with
a higher rate of thrombotic events,compared with traditional NSAID.
Use of NSAID and selective COX-2 inhibitors should be avoided in conditions associated with diminished intravascular
volume or edema,such as congestive heart failure,nephrotic syndrome,or cirrhosis and in patients with unacceptable serum creatinine
All patients with RA ar candidates for DMARD therapy. Although NSAIDs and glucocorticoids may alleviate symptoms,joint
damage may continue to occur and to progress. DMARDs have the potential to potential to reduce or prevent joint damage preserve
joint integrity and function and ultimately reduce the total costs of health care and maintain economic productivity of the
patient with RA.
The initiation of DMARD therapy should not be delayed beyond 3 months for any patient with an established diagnosis,who,despite
adequate treatment with NSAIDs has ongoing joint pain,significant morning stiffness or fatigue,active synovitis,persistent
elevation of the ESR or CRP level,or radiographic joint damage. For any untreated patient with persistent synovitis
and joint damage,DMARD treatment should be started promptly to prevent or slow further damage.
For 60 to 90% of patients the disease is progressive despite treatment, leading to disability and early mortality. This
group of patients often shows extra-articular manifestations of the disease (e.g. vasculitis which can involve skin, lung,
heart, kidney and ocular vessels).
In those with the poorest functional status and more involved joints the 5-year survival rate can be les than 50%; this
is similar to mortality in other severe diseases such as stage IV Hodgkin's disease and 3-vessel coronary artery disease.
But Not for All. Nevertheless, for a small proportion of patients (5 to 20%) the disease is mild and symptoms resolve
within 1 to 2 years after treatment with NSAIDs alone. For a further 5 to 20% of patients the disease progresses slowly and
response to DMARDs is usually satisfactory.
Although those with mild disease often have a smaller number of involved joints and rheumatoid factor is not detectable,
there is no agreed prognostic marker(s) to determine which 'type' of rheumatoid arthritis a patient is likely to have at initial
presentation. Treatment is therefore usually 'stepped up' gradually to avoid exposing patients with milder types of rheumatoid
arthritis to poorly tolerated therapies.
The goal of treatment is to control inflammation sufficiently to prevent or retard joint damage with the ultimate goal
being to induce complete remission. Unfortunately complete remission is rarely achieved. A number of criteria are used in
clinical trials to measure response to treatment and are often combined to form a composite measure of treatment response,
e.g. the American College of Rheumatology (ACR) criteria . Minimal clinical response is defined as a 20% improvement (ACR
Try NSAIDs First-NSAIDs reduce joint pain and swelling and may improve function; however, they do not alter disease
progression. Nevertheless, because of the unpredictable course of rheumatoid arthritis at presentation they are usually used
as initial treatment. If patients continue to experience persistent joint symptoms, morning stiffness, and fatigue for more
than 3 months, treatment with DMARDs is indicated.
Delaying treatment with DMARDs until joint damage is evident was found to be associated with poor long term outcomes.
The current treatment strategy therefore involves the early use of DMARDs to limit joint damage and preserve function. The
term DMARD applies to a diverse array of drugs such as penicillamine, oral or intramuscular gold, sulfasalazine, antimalarials
(chloroquine and hydroxychloroquine) and immunosuppressants (methotrexate, azathioprine, cyclosporin, leflunomide).
There is typically a delay in onset of clinical efficacy with these drugs which ranges from 4 weeks to 6 months depending
on the DMARD being used. Adverse events are a major limitation of the use of DMARDs and monitoring of complete blood counts
is recommended for all DMARDs (except hydroxy-chloroquine and leflunomide). Additional monitoring of liver function
tests, serum creatinine and urine proteins is required for some DMARDs. The cost of adverse event monitoring adds significantly
to the cost of treatment with these agents.
Nevertheless, the consequences of rheumatoid arthritis are so severe that the efficacy/toxicity ratio of drugs such as
methotrexate, sulfasalazine and hydroxychloroquine appears to be favourable. Such treatments are best administered by specialist
Among the older DMARDs, methotrexate appears to have the best long term efficacy and is often selected as the initial
DMARD. This observation conflicts with the registered indication which is for patients with severe, acute disease who do not
respond to a course of NSAIDs and at least one other DMARD. This caution is a reflection of the potentially serious adverse
events associated with this drug including an increased risk of lymphoma.
Despite methotrexate's ability to reduce disease activity and joint damage, it rarely leads to true remission and combination
therapy is frequently required.
Leflunomide is a more recently introduced DMARD. Over longer treatment durations (24 months), leflunomide appeared to
be at least as effective as methotrexate and more effective than sulfasalazine. Leflunomide also delayed radiological progression,
assessed after 12 or 24 months of treatment, at least as effectively as methotrexate (in some patients ) or sulfasalazine
and reduced functional disability (assessed using a Health Assessment Questionnaire) to a greater extent than either methotrexate
or sulfasalazine after treatment durations of 6 to 24 months. The drug had a faster onset of action (4 weeks) than either
methotrexate or sulfasalazine and was as well tolerated as both of these drugs in clinical trials.
Infliximab and etanercept have recently been approved for use in the treatment of rheumatoid arthritis ( 5 years ).Both
drugs have been shown to reduce disease activity and joint damage so can be considered as DMARDs. However, unlike the more
traditional DMARDs these drugs directly target TNF, a proinflammatory cytokine, which plays a key role in the pathological
inflammatory process in rheumatoid arthritis. Both drugs have a faster onset of action (1 to 2 weeks) compared with other
They have been associated with an increased risk of upper respiratory tract infection and more rarely with cases
of serious infection. For this reason they should not be given to patients with active infections and should be discontinued
if a patient develops a serious infection or sepsis. Approximately 10% of patients receiving infliximab have developed antibodies
to the drug but the clinical significance of this is not yet known.
In contrast, etanercept antibodies have only rarely been reported in etanercept-treated patients. Antinuclear antibodies
and anti-double-stranded DNA antibodies ( Lupus )have been reported to occur more frequently in both etanercept and infliximab
treated patients compared with placebo recipients, although drug-induced lupus has been reported in only 2 rheumatoid arthritis
patients (both of whom were receiving infliximab).
Etanercept approved for use alone. Etanercept was the first TNFinhibitor to be approved for rheumatoid arthritis. It
produced improvements in all components included in the ACR core set of disease activity measures in patients who had
failed to respond to conventional DMARD therapy, when used alone (at a dosage of 25mg subcutaneously twice weekly) or in combination
with oral or subcutaneous methotrexate (10 to 25 mg/week).
Etanercept (25mg twice weekly) was also at least as effective and well tolerated as methotrexate (7.5 mg/week increasing
to a maximum of 20 mg/week) in a large double-blind comparative trial of patients with active rheumatoid arthritis who had
not previously received methotrexate. Furthermore, etanercept reduced joint erosion significantly more effectively than methotrexate
after 6 and 12 months of treatment in the same study ( the curve seems to drop on a longer term trial ). Overall, etanercept
has been well tolerated with injection site reactions being the most frequently reported adverse event occurring in up to
49% of patients receiving the 25mg twice weekly dose.
Infliximab for use with methotrexate. Infliximab, a chimeric mouse-human monoclonal antibody directed at TNF, has primarily
been evaluated in combination with methotrexate and is therefore only approved for use in combination with this drug.
Infliximab (3 or 10 mg/kg intravenously every 4 or 8 weeks) plus methotrexate (15 mg/week orally) elicited a greater response
in ACR criteria after 30 weeks of treatment than methotrexate alone in a double-blind, placebo-controlled trial.
All patients enrolled had failed to respond to more than 1 DMARD. Preliminary data indicate that response is sustained
for up to 54 weeks and that joint damage is reduced compared with methotrexate alone. Adverse events, including serious events,
occurred more frequently in infliximab-treated patients than in the placebo group ).
If residual inflammation remains after maximum doses of DMARD monotherapy, combinations of DMARDs should be considered.
Methotrexate is the drug most commonly used in combination. These studies generally indicate increased efficacy for combination
therapy compared with monotherapy and tolerability does not appear to be increased. The use of combination regimens is becoming
more common for the treatment of patients with refractory rheumatoid arthritis but long term follow-up (5 years) is still
needed to determine optimum strategies.
There's no point beating around the bush: If you have arthritis,you'll almost inevitably require some medication. That
could mean daily,and for the rest of your life.
To minimize your risks and maximize your benefits, you're going to have to become an enlightened consumer and learn to
work as part of a team with your doctor and your other health care workers.
Consider this scenario: You haven't been feeling well for some time-persistent joint pain,flulike malaise and morning
stiffness. You see your family physician who does a physical exam and order some lab test. May even give you a pill.
At a follow-up appointment,your doctor announces that you may have rheumatoid arthritis (RA),and an appointment is being
set up with a specialist. In the meantime,he says,have your pharmicist fill out this prescription and follow instructions
on the label. You're so stunned by the diagnosis you barely absorb what the doctor has said.
You follow instructions blindly,not knowing what to expect, and, several months later-just as you're starting to feel
some-what better-you're totally unprepared for the "flare-up" that appears. Or you throw away the pills and the RA gets worse.
Or you take the pills "when you feel like it" .
Certainly,your doctor is confused. You're not getting worse,you're not getting any better.and she starts adjusting your
treatment regimen...again !
Here's an alternative. Learn everything you can about your condition, become a arthritis self-manager,someone who knows
about "risk-to-benifit ratios","optimum blood serum levels".and "indications and contraindictions".
Now you know what you're medications are supposed to do,when,and why. You know what to do if it doesn't work,and what
side effects to watch for-which can be serious-and which in most cases can be dealt with a change in dose ,the way it is delivered
or a change in medication.
You're not buffeted by every change in your condition. You're less anxious and far less fearful You will actually have
less pain. You're in control of the disease. You've made yourself an very important member of the health care team ! Actually,a
Rheumatoid arthritis patients have variable disease courses,therapy needs to be tailored for each individual. After diagnosis,it
is important for the physician and patient to devise a treatment plan together. Since RA is an ongoing disorder involving
the entire body,therapy is many-sided and includes both medication-based and non-medication-based treatments.
The treatment plan generally requires a team approach with other professionals ,including nurses,physical and occupational
therapists,orthopedic surgeons,psychologists and social workers, when applicable,depending upon patient needs.
Medication management of patients diagnosed with RA involves an initial assessment of disease stage and activity level.
For patients with early mild disease,treatment with NSAIDs and continued rigourous evaluation of progression of disease
is necessary. For patients with active,progressive disease,early aggressive therapy with DMARDs is indicated.
Therapy other than medications is a critical element of treatment for the RA patient A team approach with health providers
is essential,both rest and exercise help in important ways. People with RA need a good balance between the two,with more
rest when the disease is active and more exercise when it is not.
Rest fights fatigue and helps reduce active joint inflammation and pain The length of time needed to rest will vary from
person to person,but in general, occassional short rest breaks are more helpful than long periods spent in bed.
Exercise is important maintaining strong muscles and flexibility and preserving joint mobility. Exercise also helps people
sleep well,reduce pain,maintain a positive attitude,and lose excessive weight. Exercise programs should be planned and carried
out to take into consideration the person's physical abilities,limitations,and changing needs.
During the course of RA,particular attention should be paid to maintaining functional status. This often requires input
from physical and occupational therapists. With the exception of several specific types of oils (including omega 3 fatty acids),there
is no evidence that any specific food or nutrient helps most people with RA.
However,an nutritious overall diet with appropriate calories, protein and calcium is important. Some patients need to
avoid alcohol consumption because of medication interactions. Physician and dietician guidance on this issue is important
Osteoporosis prevention is an issue that needs to be addressed as part of long-tem.ongoing care. RA substantially increases
the risk of osteoporosis. This risk is further increased if patients are taking corticosteriods such as predisone.
The benefits of calcium and vitamin D supplements,hormone replacement therapy,or other treatments (such as bisphosphonate
therapy) for osteoporosis should be discussed. Patients who are well informed and participate actively in their own treatment
experience less pain and make fewer visits to the doctor than those who are not actively involved in their own treatment.
In some patients with advanced RA,joint destruction may occur despite appropiate non-surgecal attempts to preserve joint
function. Surgery is necessary once a patient suffers significant functional decline on the basis of joint destruction or
once the patient experiences relenting pain.
Herbs are the basis for many traditional medications as aspirin and morphine. Practisioners of some complementary therapies
believe that certain herbs have anti-inflammatory properties. These herbs include cumin,coriander, celery, evening primrose
oil turmic,devil's claw,thunder god vine, feverfew, capsicum, cinammon,yucca.dandelioin and ginger.
Little research has been conducted on the plant's effectiveness. The results from clinical trials of evening primrose
rose and capsicum for RA have been mixed. A trial for ginger as a treatment for OA found it may be useful A dieabitic should
not use ginger. Research into turmeric,devil's claw,feverfew and willow found no benefit for the inflammation that occurs
For centuries,Chinese practisioners have used the herbal remedy tripterygium wilfordii hook f (TWHF) to treat inflammation
and musculosketal injuries. TWHF is a vinelike plant found in southern China. However,TWHF can be toxic at high doses
(as many herbal products are) it can cause heart damage, kidney failure,intestinal problems,shock,decreased sperm production
and menstrual irregularities.
The toxicity and drug interactions with other medication can have serious,dire consequences. Furthermore,herbs are unregulated
and inappopriate dosing can have many unforseen consequences.
Research may someday help carve a niche for some herbs in arthritis treatment. For now,remember that many herbs contain
powerful substances that can be toxic and interfere with medications.
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 adequate.