Rheumatoid Arthritis (RA)

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Rheumatoid Arthritis (RA)





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acetaminophen


arthritis


azathioprine


betamethasone


corticosteroid


cyclophosphamide


cyclosporine


dexamethasone


eczema


episcleritis


gastrointestinal


hepatitis


hydrocortisone


hydroxychloroquine


idiopathic


lansoprazole


lymphocytes


methotrexate


naproxen


necrosis


omeprazole


osteoarthritis


osteoporosis


pericardium


prednisone


psoriasis


rhinitis


scleritis


sclerosis


sulfasalazine


triamcinolone


vasculitis








Rheumatoid arthritis is an inflammatory arthritis in which joints, usually including those of the hands and feet, are inflamed, resulting in swelling, pain, and often destruction of joints.


The immune system damages the joints and connective tissues.
Joints (typically the small joints of the limbs) become painful and have stiffness that persists for more than 60 minutes on awakening and after inactivity.
Fever, weakness, and damage to other organs may occur.
Diagnosis is based mainly on symptoms, but also on blood tests for rheumatoid factor and on x-rays.
Treatment can include exercises and splinting, drugs (nonsteroidal anti-inflammatory drugs [NSAIDs], disease-modifying antirheumatic drugs, and immunosuppressive drugs), and surgery.

Worldwide, rheumatoid arthritis develops in about 1% of the population, regardless of race or country of origin, affecting women 2 to 3 times more often than men. Usually, rheumatoid arthritis first appears between 35 years and 50 years of age, but it may occur at any age. A disorder similar to rheumatoid arthritis can occur in children. The disease is then called juvenile idiopathic arthritis, and the symptoms and prognosis are often somewhat different (see Juvenile Idiopathic Arthritis (JIA)).

The exact cause of rheumatoid arthritis is not known. It is considered an autoimmune disease (see Autoimmune Disorders). Components of the immune system attack the soft tissue that lines the joints and can also attack connective tissue in many other parts of the body, such as the blood vessels and lungs. Eventually, the cartilage, bone, and ligaments of the joint erode, causing deformity, instability, and scarring within the joint. The joints deteriorate at a variable rate. Many factors, including genetic predisposition, may influence the pattern of the disease. Unknown environmental factors (such as viral infections) are thought to play a role.

Symptoms

People with rheumatoid arthritis may have a mild course, occasional flare-ups with long periods of remission (in which the disease is inactive), or a steadily progressive disease, which may be slow or rapid. Rheumatoid arthritis may start suddenly, with many joints becoming inflamed at the same time. More often, it starts subtly, gradually affecting different joints. Usually, the inflammation is symmetric, with joints on both sides of the body affected about equally. Typically, the small joints in the fingers, toes, hands, feet, wrists, elbows, and ankles become inflamed first. The inflamed joints are usually painful and often stiff, especially just after awakening (such stiffness generally lasts for more than 60 minutes) or after prolonged inactivity. Some people feel tired and weak, especially in the early afternoon. Rheumatoid arthritis may cause a loss of appetite with weight loss and a low-grade fever.

Affected joints are tender, warm, red, and enlarged because of swelling of the soft tissue and sometimes fluid within the joint. Joints can quickly become deformed. Joints may freeze in one position so that they cannot bend or open fully. The fingers may tend to dislocate slightly from their normal position toward the little finger on each hand, causing tendons in the fingers to slip out of place.

Swollen wrists can pinch a nerve and result in numbness or tingling due to carpal tunnel syndrome (see Hand Disorders: Carpal Tunnel Syndrome). Cysts, which may develop behind affected knees, can rupture, causing pain and swelling in the lower legs. Up to 30% of people with rheumatoid arthritis have hard bumps (called rheumatoid nodules) just under the skin, usually near sites of pressure (such as the back of the forearm near the elbow).

Rarely, rheumatoid arthritis causes an inflammation of blood vessels (vasculitis—see Vasculitic Disorders: Introduction). This condition reduces the blood supply to tissues and may cause nerve damage or leg sores (ulcers). Inflammation of the membranes that cover the lungs (pleura) or of the sac surrounding the heart (pericardium) or inflammation and scarring of the lungs or heart can lead to chest pain or shortness of breath. Some people develop swollen lymph nodes; Sjögren's syndrome, which consists of dry eyes, mouth, vagina, or a combination (see Autoimmune Disorders of Connective Tissue: Sjögren's Syndrome); or red, painful eyes caused by inflammation (episcleritis).




Did You Know...

It is rare for specific foods to cause flare-ups of rheumatoid arthritis.


Diagnosis

In addition to the important characteristic pattern of symptoms, the doctor may use the following to support the diagnosis: laboratory tests, an examination of a joint fluid sample obtained with a needle, and even a biopsy (removal of a tissue sample for examination under a microscope) of rheumatoid nodules. Characteristic changes in the joints may be seen on x-rays. Magnetic resonance imaging (MRI) seems to be more sensitive and detects joint abnormalities earlier but is not usually necessary for making the diagnosis.

Blood Tests: In 9 of 10 people who have rheumatoid arthritis, the erythrocyte sedimentation rate (ESR—a test that measures the rate at which red blood cells settle to the bottom of a test tube containing blood) is increased, which suggests that active inflammation is present. However, similar increases in the ESR occur in many other disorders. Doctors may monitor the ESR to help determine whether the disease is active.

Many people with rheumatoid arthritis have distinctive antibodies in their blood, such as rheumatoid factor, which is present in 70% of people with rheumatoid arthritis. (Rheumatoid factor also occurs in several other diseases, such as hepatitis and some other infections. Some people even have rheumatoid factor in their blood without any evidence of disease.) Usually, the higher the level of rheumatoid factor in the blood, the more severe the rheumatoid arthritis and the poorer the prognosis. The rheumatoid factor level may decrease when joints are less inflamed.

Anti-citrullinated peptide (anti-CCP) antibodies are present in 96% of people who have rheumatoid arthritis and are almost always absent in people who do not have rheumatoid arthritis. Doctors are starting to use tests for anti-CCP antibodies to help diagnose rheumatoid arthritis.

Most people have mild anemia (an insufficient number of red blood cells—see Anemia: Introduction). Rarely, the white blood cell count becomes abnormally low. When a person with rheumatoid arthritis has a low white blood cell count and an enlarged spleen, the disorder is called Felty's syndrome.

Prognosis

The course of rheumatoid arthritis is unpredictable. The disorder progresses most rapidly during the first 6 years, particularly the first year, and 80% of people develop permanent joint abnormalities within 10 years. Rheumatoid arthritis may decrease life expectancy by 3 to 7 years. Heart disease, infection, gastrointestinal bleeding, drug treatment, cancer, and the underlying disease may be responsible. Rarely, rheumatoid arthritis resolves spontaneously.

Treatment relieves symptoms in 3 of 4 people; however, at least 10% are eventually severely disabled despite full treatment. Factors that tend to predict a poorer prognosis include the following:

Being white, a woman, or both
Having rheumatoid nodules
Being older when the disorder begins
Having inflammation in 20 or more joints
Having a high ESR
Having high levels of rheumatoid factor or anti-CCP

Treatment

Treatments include simple, conservative measures in addition to drugs and surgical treatments. Simple measures are meant to help the person's symptoms and include rest and adequate nutrition. Because disease-modifying antirheumatic drugs (DMARDs) may actually slow progression of the disease as well as relieve symptoms, they are often started soon after the diagnosis of rheumatoid arthritis is made.

Severely inflamed joints should be rested, because using them can aggravate the inflammation. Regular rest periods often help relieve pain, and sometimes a short period of bed rest helps relieve a severe flare-up in its most active, painful stage. Splints can be used to immobilize and rest one or several joints, but some systematic movement of the joints is needed to prevent adjacent muscles from weakening and joints from freezing in place.

A regular, healthy diet is generally appropriate. A diet rich in fish and plant oils but low in red meat can have small beneficial effects on the inflammation. Rarely, people have flare-ups after eating certain foods, and if so, these foods should be avoided. Many diets have been proposed but have not proven helpful. Fad diets should be avoided.

The main categories of drugs used to treat rheumatoid arthritis are the nonsteroidal anti-inflammatory drugs (NSAIDs), DMARDs, corticosteroids, and immunosuppressive drugs. Newer drugs include leflunomide Some Trade Names
ARAVA
, anakinra (an interleukin-1 receptor antagonist), tumor necrosis factor (TNF)-inhibiting drugs, and other drugs that modify the immune response (immunosuppressive drugs). Generally, stronger drugs have potentially serious side effects that must be looked for during treatment.


Drugs Used to Treat Rheumatoid Arthritis


Type Drug Selected Side Effects Comments
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Diclofenac Some Trade Names
CATAFLAM
VOLTAREN

Ibuprofen Some Trade Names
ADVIL
MOTRIN
NUPRIN

Naproxen Some Trade Names
ALEVE
ANAPROX

Many others (see Pain: Opioid Analgesics)
Upset stomach

Stomach ulcers

Increased blood pressure

Kidney problems

Possibly increased risk of heart attack and stroke
All NSAIDs treat the symptoms and decrease inflammation but do not alter the course of the disease.

Cyclooxygenase-2 (COX-2) inhibitors (coxibs), such as celecoxib Some Trade Names
CELEBREX

Risk of kidney problems

Increased blood pressure

Less risk of stomach ulcer than with other NSAIDs

Possible increased risk of heart attack and stroke

Disease-modifying antirheumatic drugs (DMARDs)
All DMARDs can slow progression of joint damage as well as gradually decrease pain and swelling.

Hydroxychloroquine Some Trade Names
PLAQUENIL

Usually mild:

Rashes

Muscle aches

Eye problems


Methotrexate Some Trade Names
RHEUMATREX

Liver disease

Lung inflammation

Nausea

Increased susceptibility to infection

Suppression of blood cell production in the bone marrow

Mouth sores

Decreased semen

Hair loss


Sulfasalazine Some Trade Names
AZULFIDINE

Suppression of blood cell production in the bone marrow

Stomach upset

Liver problems

Rashes

Corticosteroids
Prednisone Some Trade Names
DELTASONE
METICORTEN

Numerous side effects throughout the body with long-term use:

Weight gain

Diabetes

High blood pressure

Thinning of bones
Prednisone Some Trade Names
DELTASONE
METICORTEN
can reduce inflammation quickly.

It may not be useful long term because of side effects.

Immunosuppressive drugs
Azathioprine Some Trade Names
IMURAN

Cyclophosphamide Some Trade Names
CYTOXAN

Cyclosporine Some Trade Names
SANDIMMUNE
NEORAL

Leflunomide Some Trade Names
ARAVA

Liver disease

An increased susceptibility to infection and possibly cancer

Suppression of blood cell production in the bone marrow

Rashes and liver disease with leflunomide Some Trade Names
ARAVA

Azathioprine Some Trade Names
IMURAN
, cyclophosphamide Some Trade Names
CYTOXAN
, and cyclosporine Some Trade Names
SANDIMMUNE
NEORAL
are about as effective as other DMARDs but are more toxic.

Cyclosporine Some Trade Names
SANDIMMUNE
NEORAL
does not affect the blood count but can reduce kidney function.

Leflunomide Some Trade Names
ARAVA
is about as effective as methotrexate Some Trade Names
RHEUMATREX
.

Adalimumab*

Etanercept Some Trade Names
ENBREL

Infliximab Some Trade Names
REMICADE

Potential risk of infection (particularly tuberculosis) or cancer

Liver disease

Suppression of blood cell production in the bone marrow
These drugs produce a dramatic, prompt response in most people.

They can slow joint damage.

Anakinra
Pain and itching at injection site

Infection

Increased risk of infection and possibly cancer

Suppression of blood cell production in the bone marrow
Anakinra is probably less effective than adalimumab, etanercept Some Trade Names
ENBREL
, and infliximab Some Trade Names
REMICADE
.

Rituximab Some Trade Names
RITUXAN

When the drug is being given:

Itching at injection site

Rashes

Back pain

High or low blood pressure

Fever

After the drug is given:

Increased risk of infection and possibly cancer

Suppression of blood cell production in the bone marrow
Rituximab Some Trade Names
RITUXAN
is used only when people do not improve after taking a tumor necrosis factor inhibitor and methotrexate Some Trade Names
RHEUMATREX
.

Abatacept
Infection

Headache

Upper respiratory infection

Sore throat

Nausea
Abatacept is used only when people do not improve after taking other drugs.

*Adalimumab, etanercept Some Trade Names
ENBREL
, and infliximab Some Trade Names
REMICADE
are tumor necrosis factor inhibitors.


Nonsteroidal Anti-Inflammatory Drugs: NSAIDs (see Pain: Nonsteroidal Anti-Inflammatory Drugs) are commonly used to treat the symptoms of rheumatoid arthritis. They do not prevent the damage caused by rheumatoid arthritis from progressing and thus should not be considered the primary treatment. NSAIDs can reduce the swelling in affected joints and relieve pain. Rheumatoid arthritis, unlike osteoarthritis, causes considerable inflammation. Thus, drugs that decrease inflammation, including NSAIDs, have an important advantage over drugs such as acetaminophen Some Trade Names
TYLENOL
that reduce pain but not inflammation. However, all NSAIDs (including aspirin Some Trade Names
ECOTRIN
ASPERGUM
) cause side effects and can upset the stomach and cannot be taken by anyone who has active digestive tract (peptic) ulcers—including stomach ulcers or duodenal ulcers. Drugs called protein pump inhibitors (such as esomeprazole, lansoprazole Some Trade Names
PREVACID
, omeprazole Some Trade Names
PRILOSEC
, pantoprazole Some Trade Names
PROTONIX
, and rabeprazole Some Trade Names
ACIPHEX
) can reduce the risk of stomach or duodenal ulcers. Other possible side effects of NSAIDs may include headache, confusion, worsening of high blood pressure, worsening of kidney function, and swelling. People who get hives or asthma after they take aspirin Some Trade Names
ECOTRIN
ASPERGUM
may have the same symptoms after taking other NSAIDs. NSAIDs may increase the risk of heart attacks and strokes. The risk appears to be higher if the drug is used at higher doses and for longer periods of time. The risk is higher with certain NSAIDs than others.

Aspirin Some Trade Names
ECOTRIN
ASPERGUM
is no longer used to treat rheumatoid arthritis because effective doses are often toxic.

The cyclooxygenase (COX-2) inhibitors (coxibs, such as celecoxib Some Trade Names
CELEBREX
) are NSAIDs that act similarly to the other NSAIDs but are less likely to damage the stomach. However, if a person takes aspirin Some Trade Names
ECOTRIN
ASPERGUM
, stomach damage is almost as likely to occur as with other NSAIDs. Caution should be taken with use of coxibs and probably all NSAIDs for long periods or by people with risk factors for heart attack and stroke.

Disease-Modifying Antirheumatic Drugs (DMARDs): DMARDs, such as methotrexate Some Trade Names
RHEUMATREX
, hydroxychloroquine Some Trade Names
PLAQUENIL
, and sulfasalazine Some Trade Names
AZULFIDINE
, slow the progression of rheumatoid arthritis and sometimes can improve the course of the disease, although most take weeks or months to have an effect. These drugs are usually added promptly after the diagnosis of rheumatoid arthritis is made. Even if pain is decreased with NSAIDs, a doctor will likely prescribe a DMARD because the disease progresses even if symptoms are absent or mild.

About 66% of people improve overall, but complete remissions are uncommon. The progression of arthritis usually slows, but pain may remain. People should be made fully aware of the risks of DMARDs and monitored carefully for evidence of toxicity.

Combinations of DMARDs may be more effective than single drugs. For example, hydroxychloroquine Some Trade Names
PLAQUENIL
, sulfasalazine Some Trade Names
AZULFIDINE
, and methotrexate Some Trade Names
RHEUMATREX
together are more effective than methotrexate Some Trade Names
RHEUMATREX
alone or the other two together. Also, combining certain immunosuppressant drugs with a DMARD is often more effective than using a single drug or certain combinations of DMARDs. For example, methotrexate Some Trade Names
RHEUMATREX
can be combined with a TNF inhibitor.

Methotrexate Some Trade Names
RHEUMATREX
is taken by mouth once weekly. It is anti-inflammatory at the low doses used to treat rheumatoid arthritis. It is very effective and begins to work within a few weeks, which is relatively rapid for a DMARD. If a person has liver dysfunction or diabetes and takes methotrexate Some Trade Names
RHEUMATREX
, frequent doctor visits and blood tests may be warranted so that possible side effects can be detected early. The liver can scar, but this most often can be detected and reversed before major damage develops. People must refrain from drinking alcohol to minimize the risk of liver damage. Bone marrow suppression (suppression of the production of red blood cells, white blood cells, and platelets) is possible. Blood counts should be tested about every 2 months in all people taking the drug. Inflammation of the lung is rare but potentially fatal. Inflammation in the mouth and nausea can also develop. Severe relapses of arthritis can occur after methotrexate Some Trade Names
RHEUMATREX
is discontinued. Folate (folic acid) tablets may decrease some of the side effects, such as mouth ulcers.

Hydroxychloroquine Some Trade Names
PLAQUENIL
is given daily by mouth. Side effects, which are usually mild, include rashes, muscle aches, and eye problems. However, some eye problems can be permanent, so people taking hydroxychloroquine Some Trade Names
PLAQUENIL
must have their eyes checked by an ophthalmologist before treatment begins and every 6 to 12 months during treatment. If the drug has not helped after 9 months, it is discontinued. Otherwise, hydroxychloroquine Some Trade Names
PLAQUENIL
can be continued as long as necessary.

Sulfasalazine Some Trade Names
AZULFIDINE
tablets can relieve symptoms and slow the development of joint damage. Sulfasalazine Some Trade Names
AZULFIDINE
can also be used in people who have less severe rheumatoid arthritis or added to other drugs to boost their effectiveness. The dose is increased gradually, and improvement usually is seen within 3 months. Like the other DMARDs, it can cause stomach upset, liver problems, blood cell disorders, and rashes.

Gold Some Trade Names
MYOCHRYSINE
compounds are not used anymore.

Corticosteroids: Corticosteroids, such as prednisone Some Trade Names
DELTASONE
METICORTEN
, are the most dramatically effective drugs for reducing inflammation anywhere in the body. Although corticosteroids are effective for short-term use, they may become less effective over time, and rheumatoid arthritis is usually active for years.

There is some controversy as to whether corticosteroids can slow the progression of rheumatoid arthritis. Furthermore, the long-term use of corticosteroids almost invariably leads to side effects, involving almost every organ in the body. Consequently, doctors usually reserve corticosteroids for short-term use when beginning treatment for severe symptoms (until a DMARD has taken effect) or in severe flare-ups when many joints are affected. They are also useful in treating inflammation outside of joints, for example, in the membranes covering the lungs (pleura) or in the sac surrounding the heart (pericardium). Because of the risk of side effects, the lowest effective dose is almost always used. When injected into a joint, the person does not get the same side effects as when taking a corticosteroid by mouth (oral) or vein (intravenously). Corticosteroids can be injected directly into affected joints for fast, short-term relief.

People who have peptic ulcer disease, high blood pressure, infections, diabetes, and glaucoma should use oral or intravenous corticosteroids only when being closely monitored for side effects by their doctor.












Corticosteroids: Uses and Side Effects
Corticosteroids are the strongest drugs available for reducing inflammation in the body. They are useful in any condition in which inflammation occurs, including rheumatoid arthritis and other connective tissue disorders, multiple sclerosis, and in emergencies such as brain swelling due to cancer, asthma attacks, and severe allergic reactions. When inflammation is severe, use of these drugs is often life saving.

Corticosteroids can be given by vein (especially in emergency situations), taken by mouth, or directly applied to the inflamed organ (as in inhaled versions for the lungs, in eye drops, and in a skin cream). For example, corticosteroids can be used as an inhaled preparation for treatment of asthma. They can be used as a nasal spray to treat hay fever (allergic rhinitis). They can be used as eye drops to treat eye inflammation (uveitis). They may be applied directly to an affected area for treatment of certain skin conditions such as eczema and psoriasis.

Corticosteroids are prepared synthetically to have the same action as cortisol Some Trade Names
CORTEF
HYDROCORTONE
(or “cortisone”), a steroid hormone produced by the outer layer (cortex) of the adrenal glands—hence the name “corticosteroid.” Many synthetic corticosteroids are, however, more powerful than cortisol Some Trade Names
CORTEF
HYDROCORTONE
, and most are longer acting. Corticosteroids are chemically related to, but have different effects than, anabolic steroids (such as testosterone Some Trade Names
DELATESTRYL
DEPOTESTOSTERONE
) that are produced by the body and sometimes abused by athletes.

Examples of corticosteroids include prednisone Some Trade Names
DELTASONE
METICORTEN
, dexamethasone Some Trade Names
DECADRON
HEXADROL
, triamcinolone Some Trade Names
ARISTOCORT
KENACORT
KENALOG
, betamethasone Some Trade Names
CELESTONE
UTICORT
VALISONE
, beclomethasone Some Trade Names
BECONASE
VANCENASE
, flunisolide Some Trade Names
NASALIDE
, and fluticasone Some Trade Names
CUTIVATE
FLONASE
FLOVENT
. All of these drugs are very strong (although strength depends on the dose used). Hydrocortisone Some Trade Names
See Cortisol
is a milder corticosteroid that is available in over-the-counter skin creams.

Because corticosteroids reduce the body's ability to fight infections by suppressing inflammation, they are used with extreme care when infections are present. Their use may worsen high blood pressure, heart failure, diabetes, peptic ulcers, and osteoporosis. Therefore, corticosteroids are used in such conditions only when their benefit is likely to exceed their risk.

When they are taken by mouth or by injection for more than about 2 weeks, corticosteroids should not be discontinued abruptly. This is because corticosteroids inhibit the production of cortisol Some Trade Names
CORTEF
HYDROCORTONE
by the adrenal glands, and this production must be given time to recover. Thus, at the end of a course of corticosteroids, the dose is gradually reduced. It is important for a person who takes corticosteroids to follow the doctor's instructions on dosage very carefully.

The long-term use of corticosteroids, particularly at higher doses and particularly when given by mouth or vein, invariably leads to many side effects, involving almost every organ in the body. Common side effects include thinning of the skin with stretch marks and bruising, high blood pressure, elevated blood sugar levels, cataracts, puffiness in the face (moon face) and abdomen, thinning of the arms and legs, poor wound healing, stunted growth in children, loss of calcium from the bones (which can lead to osteoporosis), hunger, weight gain, and mood swings. Because most of their effects are caused locally, inhaled corticosteroids and those that are applied directly to the skin cause far fewer side effects than the version given by mouth or that given by vein.



Immunosuppressive Drugs: Although corticosteroids suppress the immune system, other drugs do so even more potently and are referred to as immunosuppressive drugs. Each of these drugs can slow the progression of disease and decrease the damage to bones adjacent to joints. However, by interfering with the immune system, immunosuppressive drugs may increase the risks of infection and certain cancers. Such drugs include methotrexate Some Trade Names
RHEUMATREX
(which is often the first DMARD used), leflunomide Some Trade Names
ARAVA
, azathioprine Some Trade Names
IMURAN
, cyclophosphamide Some Trade Names
CYTOXAN
, cyclosporine Some Trade Names
SANDIMMUNE
NEORAL
, tumor necrosis factor (TNF) inhibitors, rituximab Some Trade Names
RITUXAN
, and abatacept.

Immunosuppressive drugs are effective in treating severe rheumatoid arthritis. They suppress the inflammation so that corticosteroids can be avoided or given in lower doses. But immunosuppressive drugs have their own potentially toxic and serious side effects, including liver disease, an increased susceptibility to infection, the suppression of blood cell production in the bone marrow, and, with cyclophosphamide Some Trade Names
CYTOXAN
, bleeding from the bladder. In addition, azathioprine Some Trade Names
IMURAN
and cyclophosphamide Some Trade Names
CYTOXAN
may increase the risk of cancer. In women who are considering pregnancy, immunosuppressive drugs should be used only after discussion with a doctor.

Leflunomide Some Trade Names
ARAVA
is a drug with benefits that are similar to those of methotrexate Some Trade Names
RHEUMATREX
but that may be less likely to cause suppression of blood cell production and lung scarring. It can be given at the same time as methotrexate Some Trade Names
RHEUMATREX
. It is given daily by mouth. The major side effects are rashes, liver dysfunction, hair loss, and diarrhea.

Etanercept Some Trade Names
ENBREL
, infliximab Some Trade Names
REMICADE
, and adalimumab are TNF inhibitors and can be dramatically effective for people who do not respond sufficiently to methotrexate Some Trade Names
RHEUMATREX
alone. Etanercept Some Trade Names
ENBREL
is given once or twice weekly by injection under the skin, and infliximab Some Trade Names
REMICADE
is given by vein every 8 weeks after loading doses. Adalimumab is injected under the skin once every 1 or 2 weeks. TNF is part of the body's immune system, so inhibition of TNF can impair the body's ability to fight infections. These drugs should be avoided in people who have active infections. Etanercept Some Trade Names
ENBREL
, infliximab Some Trade Names
REMICADE
, and adalimumab can be used with methotrexate Some Trade Names
RHEUMATREX
.

Anakinra is a recombinant interleukin-1 (IL-1) receptor antagonist, which means it interrupts one of the major chemical pathways involved in inflammation. Anakinra is given as a single daily injection. Pain and itching at the injection site are the most common side effects. IL-1 is part of the immune system, so inhibiting IL-1 can impair the ability to fight infections. Anakinra can also suppress production of white blood cells. It should not be used with TNF inhibitors.

Rituximab Some Trade Names
RITUXAN
decreases the number of B-cell lymphocytes, one of the white blood cells responsible for causing inflammation and for fighting infection. Because there is not as much evidence for the safety of rituximab Some Trade Names
RITUXAN
as many other drugs, rituximab Some Trade Names
RITUXAN
is usually reserved for people who do not improve enough after taking methotrexate Some Trade Names
RHEUMATREX
and a TNF inhibitor. It is injected in a vein, as 2 doses, 2 weeks apart. Side effects, as with other immunosuppressive drugs, may include increased risk of infections. In addition, rituximab Some Trade Names
RITUXAN
can cause effects while it is being given, such as rashes, nausea, back pain, itching, and high or low blood pressure.

Abatacept interferes with the communication between cells that coordinates inflammation. It is injected in the vein over several minutes. Abatacept is associated with several side effects and is used only for those who have not improved after using other drugs.

Other Treatments: Along with drugs to reduce joint inflammation, a treatment plan for rheumatoid arthritis should include nondrug therapies, such as exercise, physical or occupational therapy, and sometimes surgical treatment. Inflamed joints should be gently stretched so they do not freeze in one position. As the inflammation subsides, regular, active exercises can help, although a person should not exercise to the point of excessive tiredness (fatigue). For many people, exercise in water may be easier.

Treatment of tight joints consists of intensive exercises and occasionally the use of splints to gradually extend the joint. If drugs have not helped, surgical treatment may be needed. Surgically replacing knee or hip joints is the most effective way to restore mobility and function when the joint disease is advanced. Joints can also be removed or fused together, especially in the foot, to make walking less painful. The thumb can be fused to enable a person to grasp, and unstable vertebrae at the top of the neck can be fused to prevent them from compressing the spinal cord.

People who are disabled by rheumatoid arthritis can use several aids to accomplish daily tasks. For example, specially modified orthopedic or athletic shoes can make walking less painful, and devices such as grippers reduce the need to squeeze the hand forcefully.

Surgical repair must always be considered in terms of the total disease. For example, deformed hands and arms limit a person's ability to use crutches during rehabilitation, and seriously affected knees and feet limit the benefits of hip surgery. Reasonable objectives for each person must be determined, and ability to function must be considered. Surgical repair may be performed while the disease is active.

Joint repair with prosthetic joint replacement is indicated if damage severely limits function. Total hip and knee replacements are most consistently successful.

Last full review/revision February 2008 by Roy D. Altman, MD

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