| Rheumatoid arthritis (RA) is a chronic,
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| | be used early in the course of RA and is
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| potentially destructive, systemic,
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| | often used in combination with other
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| autoimmune form of arthritis. It affects
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| | DMARDs. Taking a high dose for prolonged
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| roughly 2 million Americans and has been
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| | periods has been associated with damage
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| the subject of intense research,
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| | to the retina, and an eye examination is
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| particularly in recent years.
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| | recommended for most patients every 6-12
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| The goal of treatment is to induce
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| | months.
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| remission.
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| | Sulfasalazine (SSZ) is a sulfa-based
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| In a previous article I discussed the use
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| | DMARD. It acts more quickly than
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| of non-steroidal anti-inflammatory drugs
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| | hydroxychloroquine, sometimes as early as
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| (NSAIDS) and glucocorticoids in
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| | 4 weeks. SSZ can slow x-ray progression
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| rheumatoid arthritis (RA). In this
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| | of RA and is usually well tolerated. Most
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| article I will discuss disease-modifying
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| | adverse effects (nausea and stomach
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| anti-rheumatic drugs. (DMARDS).
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| | discomfort) occur in the first few months
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| Although non-steroidal anti-inflammatory
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| | of therapy. Starting low and gradually
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| drugs (NSAIDs) and glucocorticoids
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| | increasing the dosage lessens the
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| ("steroids") may alleviate symptoms,
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| | incidence of these adverse effects. Low
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| joint damage can progress in patients
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| | white blood cell counts can occur and may
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| with active rheumatoid arthritis (RA).
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| | be serious. Periodic laboratory
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| Disease-modifying anti-rheumatic drugs
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| | monitoring is necessary. Clinical
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| (DMARDs) can reduce or prevent joint
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| | response should be apparent within 3
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| damage, preserve joint integrity and
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| | months.
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| function, and maintain the economic
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| | Leflunomide (Arava) has a slightly
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| productivity of the patient with RA.
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| | different mechanism of action than MTX
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| DMARD therapy should be considered in all
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| | and is taken in pill form once a day. It
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| patients with active RA. DMARD therapy
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| | can be used alone or with MTX, although
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| should be started immediately- certainly
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| | the risk for adverse effects (including
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| within 3 months of diagnosis- in any
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| | liver problems) is greater with this
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| patient, who has persistent joint pain,
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| | combination. The reduction in disease
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| significant morning stiffness or fatigue,
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| | activity and in the rate of x-ray
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| active joint inflammation, persistent
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| | progression by leflunomide alone is equal
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| elevation of the ESR (sed rate) or CRP
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| | to that of MTX. As with MTX, liver tests
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| level (these latter two are blood tests
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| | must be monitored closely. Five percent
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| that measure inflammation), or x-ray
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| | of patients receiving leflunomide and up
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| joint damage.
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| | to 60% of patients receiving MTX plus
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| For any untreated patient with persistent
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| | leflunomide have elevated liver enzyme
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| joint inflammation and joint damage,
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| | levels.
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| DMARD treatment should be started to
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| | Leflunomide is a potent teratogen- it
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| prevent or slow further damage.
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| | causes severe birth defects. If a patient
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| Unfortunately, all DMARDS including
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| | is planning pregnancy, the drug should be
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| methotrexate (MTX), sulfasalazine (SSZ),
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| | stopped and cholestyramine elimination
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| hydroxychloroquine (HCQ), leflunomide,
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| | performed (cholestyramine 8 g 3 times
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| azathioprine, cyclophosphamide and
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| | daily by mouth for 11 days).
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| cyclosporine require several weeks to
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| | Adherence to the package insert on
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| months before improvement begins to
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| | ridding leflunomide from the system is
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| occur.
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| | mandatory before pregnancy is considered.
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| Most rheumatologists select MTX as their
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| | Other DMARDs occasionally used in RA
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| initial DMARD of choice, particularly for
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| | include azathioprine (Imuran),
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| patients where the RA is active. Because
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| | cyclosporine (Sandimmune), and gold
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| of its efficacy, relatively low toxicity,
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| | therapy (Solganol, Myochrisine).
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| and low cost, MTX has become the standard
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| | Azathioprine and cyclosporine are
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| by which all DMARDs are compared.
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| | immunosuppressant drugs taken in pill
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| Controlled clinical trials have
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| | form. The usual dose for azathioprine is
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| established the efficacy of MTX in RA,
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| | once daily, whereas cyclosporine is
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| particularly in patients with severe
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| | generally started at twice daily.
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| disease. MTX slows the progression of
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| | Intramuscular gold injection is typically
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| x-ray damage, and more than 50% of
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| | initiated as a low test dose followed by
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| patients who take MTX continue the drug
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| | a higher weekly dose over 5-6 months.
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| beyond 3 years. Mouth sores, nausea,
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| | While many rheumatologists select
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| diarrhea, fatigue, and hair loss caused
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| | hydroxychloroquine or sulfasalazine
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| by MTX can be reduced by treating the
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| | first, MTX is usually preferred.
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| patient with folic acid supplementation.
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| | After 5 years, only 60% of patients
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| Relative contraindications for MTX
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| | remain on MTX, the best-tolerated
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| therapy are pregnancy (MTX is a potent
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| | traditional DMARD. Joint damage by x-ray
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| teratogen, meaning it causes severe birth
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| | is found in 30% of patients after 1 year
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| defects), preexisting liver disease
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| | of therapy with traditional DMARDs and in
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| -especially infectious hepatitis, kidney
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| | 70% of patients after 2 years of therapy.
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| function impairment, significant lung
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| | Joint damage by x-ray is closely
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| disease, and alcohol abuse.
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| | correlated with subsequent disability. In
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| A liver biopsy should be considered in
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| | addition, significant numbers of patients
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| patients who develop abnormal findings on
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| | on DMARD therapy may still have
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| blood liver function tests that persist
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| | progressive x-ray damage and disability.
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| during treatment or after discontinuation
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| | Numerous studies have established the
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| of MTX where no other cause for the
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| | importance of aggressive DMARDs as
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| abnormalities are found.
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| | single-drugs and as combination agent
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| MTX can be used either by itself
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| | treatments. The existence of a window of
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| (monotherapy) or in combination with
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| | opportunity is now a well-accepted
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| another DMARD.
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| | concept in RA therapeutics. This window
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| In some patients, as described above, MTX
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| | consists of the first 3-6 months of
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| is contraindicated. Not all people
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| | disease and is the optimal time to
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| respond to MTX and some people are unable
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| | initiate therapy to prevent x-ray damage
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| to tolerate it.
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| | and subsequent disability. A number of
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| In that case, other DMARDs can be used.
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| | controlled studies have advocated the use
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| Hydroxychloroquine (Plaquenil) is a mild
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| | of early aggressive DMARD therapy either
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| DMARD that may decrease the pain and
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| | alone or in combination.
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| swelling of arthritis as well as reduce
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| | In another article- Part 3- I will
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| the risk for long-term disability. It can
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| | discuss the role of biologic therapies.
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