The risk of serious side effects is low,generally speaking, in people without
existing complications (some people cannot tolerate certain medications). E.g.,MTX promises early onset of action,usually
within four to six weeks,and the liklihood of a sustained and prolonged effect. MTX is usually given as tablets,but can
also be injected into muscles. the effective weeky dose for a patient my be as low as two 2.5-milligrams tablets,as high
as ten ( subcutaneous inject is 25 mg). tablets (equivalent to 25 mg ) once a week. because the effective range is so wide,it's
best to start low ( 3 tablets a week ) and only slowly increase the dose by one tablet each time.
Changes in dose should occur no more often (approximately) than every 3 weeks,once a month is the usual. All
the pills should be taken together,at the same time,on the same day each week (There is some variations-changes in dose -longer,
and sometimes, at hgher doses,split it up into two doses per day.)
It isn't unusual to notice a god response at a farly low dose at first,but then to require a higher dose later on to
maintain that response. A complete blood count ( hemoglobin,white cell and platelet count ) is usually done every few weeks
until the final dose is decided,then every 4 to 6 weeks. Liver function test should be checked at every second blood test
(some use a different schedule).The impairment of kidney function increases the risk of any of the side effects. NSAIDs don't
interact with MTX when MTX is taken at the recommended doses,however,sulfa-containing antibodies increase the risk of side
effects and should be avoided. Side effects are often dealt with by decreasing the dose or temporarily stopping MTX and then
restarting it.
Common side effects: A 12 hr.-24-hour reaction to the dose. Nausea is most common,but some patients report flushing or
a temporry flare-up of arthritis. These reactions can be blocked by a small dose of a steriod called dexamethasone,taken with
MTX Nausea with vomiting,very occasionally occurs.
Mild anemia,and occasionally lower numbers of white blood cells or platelets,though not low enough to cause problems.
Sometimes,small sores inside the mouth for a day or two after the weekly dose. Both these and anemia of the kind menthioned
can be helped by a low dose of folic acid 5 days/week. A high dose of folic acid will counteract some of the good effects
of the MTX. (researchers found 5 days better than 7days/week).
A small amount of hair loss,noticeable on the pillow each morning but not obvious to friends and neighbours. Temporary
reduction in the sperm count n men may be caused by MTX. In women,MTX shold be avoided in pregnncy ( it can cause miscrrige
) and breast-feeding.
Rare,if you encounter these,stop MTX and call the doctor; Significant lowering of blood counts (hemoglobin,white blood
cells,platelets) with symptoms of tiredness,dizziness,infections,brusing or bleeding. cramps and diarrhea. Infection,including
pneumonia and shingles. Skin rash (very uncommon ). Occasionally patients with RA who develop rheumatoid nodules will develo
many new ones,even though the arthritis is under control.
Liver damage is very rare. To be on the side of safety,no use of alcohol (except at weddings,birthdays and Christmas-little )
since alcohol may combine with MTX to damage the liver. psoriasis,obesity and possibly diabetes may also increase the risk
of MTX liver damage.
Possible but not proved,Increased risk of infection after joint surgery ( doubtful but possible). A very few cases of
lymphoma ( a type of lymph gland cancer ) have been discovered in patients treated with MTX. It was resolved when MTX was
stopped,but it is so rare,mention this as a after-thought.
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
(Cytotec etc).
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
not recommended--ACR.
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 levels .
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.
One of the real problems in treating RA is recognizing when it's time to change the regimen. It's too easy to check a
patient breifly,mentally compare the present condition to what it was on the last visit,and continue the treatment Instead
of words of encouragement and a prescription renewal,the patient often needs a change.
Physician's memories,like anyone else,may not be the best,and patients who normally feel bad are often unaware of slow
changes. for the worse.
It's esy to monitor the condition of some diseases like blood pressure,simply put on a blood pressure pad amd take a
reading. There have been many attempts,criterias etc,to develop a similar progress test for RA,but no truly effective.fool-proof,answer
has been found.
Some patients have resistant disease and experience a progressive course,despite exhaustive trials of DMARDs whether
used alone or in combinations. While the utimate goal of treating RA is to induce complete remission,this occurs infrequently.
If complete remission is not achieved,the management goals are to control disease activity,alleviate pain,maintain function
for activities of daily living and work,and maximize quality of life. Achieving these goals challenges the managerial skills
of the rheumatologist to determine the the most efficacious combinations of pharmacological therapy,which may include NSAID,DMARD(s),low
dose predisone,local injection of glucocortoid,rehabilitation support and anagesics.Although adequate pain relief is an important
goal with a chronic disease such as RA,the ACR,does not recommend narcotic analgesic dependency.
Given the chronic waxing and waning course of RA,a longitudal treatment plan needs to be developed,and the patient should
be involved in developing the plan. The discussion should address disease progression,prognosis and treatment options,taking
into account adverse effects,expected time for response,the patient's risk factors and comorbid conditions, monitoringease
activity (i.e., ongoing disease activity after 3 months of maximum therapy ),or progressive joint damage require consideration
of significant changes in the DMARD regimen.
If disease activity is confined to one or a few joints,then local glucocortoid injection may help. For patients with
severe symptoms,systemic glucocortoids may need to be initiated,or the dosage may need to be incresed,for a short period of
time.
Active joint disease may impair physical function and may also be aggravated by physical activity. Therefore, consultation
with a physical therapist, occupational therapist and/or nurse-counselor familiar with rheumatic diseases should
be considered early in the disease course.
Periods of rest,job modification,time off from work,changes in occupation,or termination of work may be necessary. Reconstructive
surgery should be considered for patients with end-stage joint damage that is causing unacceptable pain requirements of pharmacologic
agents,and the patient's preference. Expectations for treatment and potential barriers to carrying out the recommendations
should be discussed. Psychosocial factors,such as illness beliefs and perceived self-efficacy,have been shown to affect patient
outcomes and treatment adherence Education and cognitive-behavioral interventions,such as the Arthritis Society Self-Management
Program,can improve health status and decrease visits to the physician.
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 extra-articular 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 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 earlier age at
disease onset,high titer of RF,elevted ESr,and swelling of >20 joints. Extra-articular 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.
Occasionally,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.
|