Rheumatoid Arthritis
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Rheumatoid arthritis is an inflammatory disease that causes pain,
swelling, stiffness, and loss of function in the joints. It has several special
features that make it different from other kinds of arthritis. For example,
rheumatoid arthritis generally occurs in a symmetrical pattern, meaning that
if one knee or hand is involved, the other one also is. The disease often affects
the wrist joints and the finger joints closest to the hand. It can also affect
other parts of the body besides the joints. In addition, people with rheumatoid
arthritis may have fatigue, occasional fevers, and a general sense of not feeling
well.
Rheumatoid arthritis affects people differently. For some people,
it lasts only a few months or a year or two and goes away without causing any
noticeable damage. Other people have mild or moderate forms of the disease,
with periods of worsening symptoms, called flares, and periods in which they
feel better, called remissions. Still others have a severe form of the disease
that is active most of the time, lasts for many years or a lifetime, and leads
to serious joint damage and disability.
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Features of Rheumatoid Arthritis
- Tender, warm, swollen joints
- Symmetrical pattern of affected joints
- Joint inflammation often affecting the wrist and finger joints
closest to the hand
- Joint inflammation sometimes affecting other joints, including
the neck, shoulders, elbows, hips, knees, ankles, and feet
- Fatigue, occasional fevers, a general sense of not feeling well
- Pain and stiffness lasting for more than 30 minutes in the morning
or after a long rest
- Symptoms that last for many years
- Variability of symptoms among people with the disease
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Although rheumatoid arthritis can have serious effects on a person's
life and well-being, current treatment strategies--including pain-relieving
drugs and medications that slow joint damage, a balance between rest and exercise,
and patient education and support programs--allow most people with the disease
to lead active and productive lives. In recent years, research has led to a
new understanding of rheumatoid arthritis and has increased the likelihood
that, in time, researchers will find even better ways to treat the disease.
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A joint is a place where two bones meet. The ends of the bones
are covered by cartilage, which allows for easy movement of the two bones.
The joint is surrounded by a capsule that protects and supports it. The joint
capsule is lined with a type of tissue called synovium, which produces synovial
fluid, a clear substance that lubricates and nourishes the cartilage and bones
inside the joint capsule.
Like many other rheumatic diseases, rheumatoid arthritis is an
autoimmune disease (auto means self), so-called because a person's
immune system, which normally helps protect the body from infection and disease,
attacks joint tissues for unknown reasons. White blood cells, the agents of
the immune system, travel to the synovium and cause inflammation (synovitis),
characterized by warmth, redness, swelling, and pain--typical symptoms of rheumatoid
arthritis. During the inflammation process, the normally thin synovium becomes
thick and makes the joint swollen and puffy to the touch.
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A joint (the place where two bones meet) is surrounded
by a capsule that protects and supports it. The joint capsule is lined
with a type of tissue called synovium, which produces synovial fluid
that lubricates and nourishes joint tissues. In rheumatoid arthritis,
the synovium becomes inflamed, causing warmth, redness, swelling, and
pain. As the disease progresses, the inflamed synovium invades and
damages the cartilage and bone of the joint. Surrounding muscles, ligaments,
and tendons become weakened. Rheumatoid arthritis also can cause more
generalized bone loss that may lead to osteoporosis (fragile bones
that are prone to fracture).
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As rheumatoid arthritis progresses, the inflamed synovium invades
and destroys the cartilage and bone within the joint. The surrounding muscles,
ligaments, and tendons that support and stabilize the joint become weak and
unable to work normally. These effects lead to the pain and joint damage often
seen in rheumatoid arthritis. Researchers studying rheumatoid arthritis now
believe that it begins to damage bones during the first year or two that a
person has the disease, one reason why early diagnosis and treatment are so
important.
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Some people with rheumatoid arthritis also have symptoms in places
other than their joints. Many people with rheumatoid arthritis develop anemia,
or a decrease in the production of red blood cells. Other effects that occur
less often include neck pain and dry eyes and mouth. Very rarely, people may
have inflammation of the blood vessels, the lining of the lungs, or the sac
enclosing the heart.
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Scientists estimate that about 2.1 million people, or between 0.5
and 1 percent of the U.S. adult population, have rheumatoid arthritis. Interestingly,
some recent studies have suggested that the overall number of new cases of
rheumatoid arthritis actually may be going down. Scientists are investigating
why this may be happening.
Rheumatoid arthritis occurs in all races and ethnic groups. Although
the disease often begins in middle age and occurs with increased frequency
in older people, children and young adults also develop it. Like some other
forms of arthritis, rheumatoid arthritis occurs much more frequently in women
than in men. About two to three times as many women as men have the disease.
By all measures, the financial and social impact of all types of
arthritis, including rheumatoid arthritis, is substantial, both for the Nation
and for individuals. From an economic standpoint, the medical and surgical
treatment for rheumatoid arthritis and the wages lost because of disability
caused by the disease add up to billions of dollars annually. Daily joint pain
is an inevitable consequence of the disease, and most patients also experience
some degree of depression, anxiety, and feelings of helplessness. For some
people, rheumatoid arthritis can interfere with normal daily activities, limit
job opportunities, or disrupt the joys and responsibilities of family life.
However, there are arthritis self-management programs that help people cope
with the pain and other effects of the disease and help them lead independent
and productive lives.
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Scientists still do not know exactly what causes the immune system
to turn against itself in rheumatoid arthritis, but research over the last
few years has begun to piece together the factors involved.
Genetic (inherited) factors: Scientists
have discovered that certain genes known to play a role in the immune system
are associated with a tendency to develop rheumatoid arthritis. Some people
with rheumatoid arthritis do not have these particular genes; still others
have these genes but never develop the disease. These somewhat contradictory
data suggest that a person's genetic makeup plays an important role in determining
if he or she will develop rheumatoid arthritis, but it is not the only factor.
What is clear, however, is that more than one gene is involved in determining
whether a person develops rheumatoid arthritis and how severe the disease will
become.
Environmental factors: Many scientists
think that something must occur to trigger the disease process in people whose
genetic makeup makes them susceptible to rheumatoid arthritis. A viral or bacterial
infection appears likely, but the exact agent is not yet known. This does not
mean that rheumatoid arthritis is contagious: a person cannot catch it from
someone else.
Other factors: Some scientists also think
that a variety of hormonal factors may be involved. Women are more likely to
develop rheumatoid arthritis than men, pregnancy may improve the disease, and
the disease may flare after a pregnancy. Breastfeeding may also aggravate the
disease. Contraceptive use may alter a person's likelihood of developing rheumatoid
arthritis. Scientists think that levels of the immune system molecules interleukin
12 (IL-12) and tumor necrosis factor-alpha (TNF-α) may change along with
the changing hormone levels seen in pregnant women. This change may contribute
to the swelling and tissue destruction seen in rheumatoid arthritis. These
hormones, or possibly deficiencies or changes in certain hormones, may promote
the development of rheumatoid arthritis in a genetically susceptible person
who has been exposed to a triggering agent from the environment.
Even though all the answers are not known, one thing is certain:
rheumatoid arthritis develops as a result of an interaction of many factors.
Researchers are trying to understand these factors and how they work together.
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Diagnosing and treating rheumatoid arthritis requires a team effort
involving the patient and several types of health care professionals. A person
can go to his or her family doctor or internist or to a rheumatologist. A rheumatologist
is a doctor who specializes in arthritis and other diseases of the joints,
bones, and muscles. As treatment progresses, other professionals often help.
These may include nurses, physical or occupational therapists, orthopaedic
surgeons, psychologists, and social workers.
Studies have shown that patients who are well informed and participate
actively in their own care have less pain and make fewer visits to the doctor
than do other patients with rheumatoid arthritis.
Patient education and arthritis self-management programs, as well
as support groups, help people to become better informed and to participate
in their own care. An example of a self-management program is the Arthritis
Self-Help Course offered by the Arthritis Foundation and developed at a NIAMS-supported
Multipurpose Arthritis and Musculoskeletal Diseases Center. Self-management
programs teach about rheumatoid arthritis and its treatments, exercise and
relaxation approaches, communication between patients and health care providers,
and problem solving. Research on these programs has shown that they help people:
- understand the disease
- reduce their pain while remaining active
- cope physically, emotionally, and mentally
- feel greater control over the disease and build a sense of confidence
in the ability to function and lead full, active, and independent lives.
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Rheumatoid arthritis can be difficult to diagnose in its early
stages for several reasons. First, there is no single test for the disease.
In addition, symptoms differ from person to person and can be more severe in
some people than in others. Also, symptoms can be similar to those of other
types of arthritis and joint conditions, and it may take some time for other
conditions to be ruled out. Finally, the full range of symptoms develops over
time, and only a few symptoms may be present in the early stages. As a result,
doctors use a variety of the following tools to diagnose the disease and to
rule out other conditions:
Medical history: This is the patient's
description of symptoms and when and how they began. Good communication between
patient and doctor is especially important here. For example, the patient's
description of pain, stiffness, and joint function and how these change over
time is critical to the doctor's initial assessment of the disease and how
it changes over time.
Physical examination: This includes the
doctor's examination of the joints, skin, reflexes, and muscle strength.
Laboratory tests: One common test is
for rheumatoid factor, an antibody that is present eventually in the blood
of most people with rheumatoid arthritis. (An antibody is a special protein
made by the immune system that normally helps fight foreign substances in the
body.) Not all people with rheumatoid arthritis test positive for rheumatoid
factor, however, especially early in the disease. Also, some people test positive
for rheumatoid factor, yet never develop the disease. Other common laboratory
tests include a white blood cell count, a blood test for anemia, and a test
of the erythrocyte sedimentation rate (often called the sed rate), which measures
inflammation in the body. C-reactive protein is another common test that measures
disease activity.
X rays: X rays are used to determine
the degree of joint destruction. They are not useful in the early stages of
rheumatoid arthritis before bone damage is evident, but they can be used later
to monitor the progression of the disease.
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Doctors use a variety of approaches to treat rheumatoid arthritis.
These are used in different combinations and at different times during the
course of the disease and are chosen according to the patient's individual
situation. No matter what treatment the doctor and patient choose, however,
the goals are the same: to relieve pain, reduce inflammation, slow down or
stop joint damage, and improve the person's sense of well-being and ability
to function.
Good communication between the patient and doctor is necessary
for effective treatment. Talking to the doctor can help ensure that exercise
and pain management programs are provided as needed, and that drugs are prescribed
appropriately. Talking to the doctor can also help people who are making decisions
about surgery.
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- Relieve pain
- Reduce inflammation
- Slow down or stop joint damage
- Improve a person's sense of well-being and ability to function
Current Treatment Approaches
- Lifestyle
- Medications
- Surgery
- Routine monitoring and ongoing care
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Health behavior changes: Certain activities
can help improve a person's ability to function independently and maintain
a positive outlook.
Rest and exercise: People
with rheumatoid arthritis need a good balance between rest and exercise, with
more rest when the disease is active and more exercise when it is not. Rest
helps to reduce active joint inflammation and pain and to fight fatigue. The
length of time for rest will vary from person to person, but in general, shorter
rest breaks every now and then are more helpful than long times spent in bed.
Exercise is important for maintaining
healthy and strong muscles, preserving joint mobility, and maintaining flexibility.
Exercise can also help people sleep well, reduce pain, maintain a positive
attitude, and lose weight. Exercise programs should take into account the person's
physical abilities, limitations, and changing needs.
Joint care: Some people
find using a splint for a short time around a painful joint reduces pain and
swelling by supporting the joint and letting it rest. Splints are used mostly
on wrists and hands, but also on ankles and feet. A doctor or a physical or
occupational therapist can help a person choose a splint and make sure it fits
properly. Other ways to reduce stress on joints include self-help devices (for
example, zipper pullers, long-handled shoe horns); devices to help with getting
on and off chairs, toilet seats, and beds; and changes in the ways that a person
carries out daily activities.
Stress reduction: People
with rheumatoid arthritis face emotional challenges as well as physical ones.
The emotions they feel because of the disease-fear, anger, and frustration-combined
with any pain and physical limitations can increase their stress level. Although
there is no evidence that stress plays a role in causing rheumatoid arthritis,
it can make living with the disease difficult at times. Stress also may affect
the amount of pain a person feels. There are a number of successful techniques
for coping with stress. Regular rest periods can help, as can relaxation, distraction,
or visualization exercises. Exercise programs, participation in support groups,
and good communication with the health care team are other ways to reduce stress.
Healthful diet: With
the exception of several specific types of oils, there is no scientific evidence
that any specific food or nutrient helps or harms people with rheumatoid arthritis.
However, an overall nutritious diet with enough-but not an excess of-calories,
protein, and calcium is important. Some people may need to be careful about
drinking alcoholic beverages because of the medications they take for rheumatoid
arthritis. Those taking methotrexate may need to avoid alcohol altogether because
one of the most serious long-term side effects of methotrexate is liver damage.
Climate: Some people
notice that their arthritis gets worse when there is a sudden change in the
weather. However, there is no evidence that a specific climate can prevent
or reduce the effects of rheumatoid arthritis. Moving to a new place with a
different climate usually does not make a long-term difference in a person's
rheumatoid arthritis.
Medications: Most people who have rheumatoid
arthritis take medications. Some medications are used only for pain relief;
others are used to reduce inflammation. Still others, often called disease-modifying
antirheumatic drugs (DMARDs), are used to try to slow the course of the disease.
The person's general condition, the current and predicted severity of the illness,
the length of time he or she will take the drug, and the drug's effectiveness
and potential side effects are important considerations in prescribing drugs
for rheumatoid arthritis. The table below shows currently used rheumatoid arthritis
medications, along with their uses and effects, side effects, and monitoring
requirements.
Biologic response modifiers are new drugs used for the treatment
of rheumatoid arthritis. They can help reduce inflammation and structural damage
to the joints by blocking the action of cytokines, proteins of the body's immune
system that trigger inflammation during normal immune responses. Three of these
drugs, etanercept (Enbrel*), infliximab (Remicade), and adalimumab (Humira),
reduce inflammation by blocking the reaction of TNF-α molecules. Another
drug, called anakinra (Kineret), works by blocking a protein called interleukin
1 (IL-1) that is seen in excess in patients with rheumatoid arthritis.
For many years, doctors initially prescribed aspirin or other pain-relieving
drugs for rheumatoid arthritis, as well as rest and physical therapy. They
usually prescribed more powerful drugs later only if the disease worsened.
Today, however, many doctors have changed their approach, especially
for patients with severe, rapidly progressing rheumatoid arthritis. Studies
show that early treatment with more powerful drugs, and the use of drug combinations
instead of one medication alone, may be more effective in reducing or preventing
joint damage. Once the disease improves or is in remission, the doctor may
gradually reduce the dosage or prescribe a milder medication.
* Brand names included in this booklet are provided as examples
only, and their inclusion does not mean that these products are endorsed by
the National Institutes of Health or any other Government agency. Also, if
a particular brand name is not mentioned, this does not mean or imply that
the product is unsatisfactory.
Surgery: Several types of surgery are
available to patients with severe joint damage. The primary purpose of these
procedures is to reduce pain, improve the affected joint's function, and improve
the patient's ability to perform daily activities. Surgery is not for everyone,
however, and the decision should be made only after careful consideration by
patient and doctor. Together they should discuss the patient's overall health,
the condition of the joint or tendon that will be operated on, and the reason
for, as well as the risks and benefits of, the surgical procedure. Cost may
be another factor. Commonly performed surgical procedures include joint replacement,
tendon reconstruction, and synovectomy.
Joint replacement: This
is the most frequently performed surgery for rheumatoid arthritis, and it is
done primarily to relieve pain and improve or preserve joint function. Artificial
joints are not always permanent and may eventually have to be replaced. This
may be an important consideration for young people.
Tendon reconstruction: Rheumatoid
arthritis can damage and even rupture tendons, the tissues that attach muscle
to bone. This surgery, which is used most frequently on the hands, reconstructs
the damaged tendon by attaching an intact tendon to it. This procedure can
help to restore hand function, especially if the tendon is completely ruptured.
Synovectomy: In this
surgery, the doctor actually removes the inflamed synovial tissue. Synovectomy
by itself is seldom performed now because not all of the tissue can be removed,
and it eventually grows back. Synovectomy is done as part of reconstructive
surgery, especially tendon reconstruction.
Routine Monitoring and Ongoing Care: Regular
medical care is important to monitor the course of the disease, determine the
effectiveness and any negative effects of medications, and change therapies
as needed. Monitoring typically includes regular visits to the doctor. It also
may include blood, urine, and other laboratory tests and x rays.
People with rheumatoid arthritis may want to discuss preventing
osteoporosis with their doctors as part of their long-term, ongoing care. Osteoporosis
is a condition in which bones become weakened and fragile. Having rheumatoid
arthritis increases the risk of developing osteoporosis for both men and women,
particularly if a person takes corticosteroids. Such patients may want to discuss
with their doctors the potential benefits of calcium and vitamin D supplements,
hormone therapy, or other treatments for osteoporosis.
Alternative and Complementary Therapies: Special
diets, vitamin supplements, and other alternative approaches have been suggested
for treating rheumatoid arthritis. Although many of these approaches may not
be harmful in and of themselves, controlled scientific studies either have
not been conducted on them or have found no definite benefit to these therapies.
Some alternative or complementary approaches may help the patient cope or reduce
some of the stress associated with living with a chronic illness. As with any
therapy, patients should discuss the benefits and drawbacks with their doctors
before beginning an alternative or new type of therapy. If the doctor feels
the approach has value and will not be harmful, it can be incorporated into
a patient's treatment plan. However, it is important not to neglect regular
health care. The Arthritis Foundation publishes material on alternative therapies
as well as established therapies, and patients may want to contact this organization
for information.
| Medications |
Uses/Effects |
Side Effects |
Monitoring |
| Analgesics and Nonsteroidal Anti-inflammatory
Drugs (NSAIDs) |
Analgesics relieve pain; NSAIDs relieve pain
and reduce inflammation. |
Upset stomach, peptic ulcer, bleeding, renal
failure. Use of NSAIDs may increase rate of miscarriage for pregnant
women. |
For all traditional NSAIDs: Before taking these
drugs, let your doctor know if you drink alcohol or use blood thinners
or if you have any of the following: sensitivity or allergy to aspirin
or similar drugs, kidney or liver disease, heart disease, high blood
pressure, asthma, or peptic ulcers. |
| Acetaminophen |
Nonprescription medications used to relieve pain.
Examples are aspirin-free Anacin*, Excedrin caplets, Panadol, Tylenol,
and Tylenol Arthritis. |
Usually no side effects when taken as directed. |
Not to be taken with alcohol or with other products
containing acetaminophen. Not to be used for more than 10 days unless
directed by a physician. |
Aspirin
Buffered
Plain |
Aspirin is used to reduce pain, swelling, and
inflammation, allowing patients to move more easily and carry out normal
activities. It is generally part of early and ongoing therapy. |
Upset stomach; tendency to bruise easily; ulcers,
pain, or discomfort; diarrhea; headache; heartburn or indigestion; nausea
or vomiting. |
Doctor monitoring is needed. |
| * NOTE: Brand names included in this
booklet are provided as examples only, and their inclusion does not mean
that these products are endorsed by the National Institutes of Health
or any other Government agency. Also, if a particular brand name is not
mentioned, this does not mean or imply that the product is unsatisfactory. |
Traditional NSAIDs
Ibuprofen
Ketoprofen
Naproxen |
NSAIDs help relieve pain within hours of admin-istration
in dosages available over-the-counter (available for all three medications).
They relieve pain and inflammation in dosages available in prescription
form (ibu-profen and ketoprofen). It may take several days to reduce
inflammation. |
For all traditional NSAIDs: Abdominal or stomach
cramps, pain, or discomfort; diarrhea; dizziness; drowsiness or light-headedness;
headache; heartburn or indigestion; peptic ulcers; nausea or vomiting;
possible kidney and liver damage (rare). |
For all traditional NSAIDs: Before taking these
drugs, let your doctor know if you drink alcohol or use blood thinners
or if you have or have had any of the following: sensitivity or allergy
to aspirin or similar drugs, kidney or liver disease, heart disease,
high blood pressure, asthma, or peptic ulcers. |
COX-2 Inhibitor NSAIDs
Celecoxib
Rofecoxib
Valdecoxib |
COX-2 inhibitors, like traditional NSAIDs, block
COX-2, an enzyme in the body that stimulates an inflammatory response.
Unlike traditional NSAIDs, however, they do not block the action of COX-1,
an enzyme that protects the stomach lining. This results in reduced risk
of gastro-intestinal ulceration and bleeding. Reduces joint pain and
inflammation. |
Stomach irritation, ulceration, and bleeding
may occur. Caution is advisable for patients with a history of bleeding
or ulcers, de-creased renal function, hepatic disease, hyper-tension,
or asthma. |
Use of COX-2s with low-dose aspirin is permitted
but may slightly increase ulcer risk. Doctor monitoring is recommended
before taking a COX-2 inhibitor, especially if you have had a heart attack,
stroke, angina, blood clot, hypertension, or sensitivity to aspirin or
other NSAIDs. Doctor monitoring for possible allergic responses to valdecoxib
and celecoxib is important. |
| Corticosteroids |
These are steroids given by mouth or injection.
They are used to relieve inflammation and reduce swelling, redness, itching,
and allergic reactions. |
Increased appetite, indigestion, nervousness,
or restlessness. |
For all corticosteroids, let your doctor know
if you have one of the following: fungal infection, history of tuberculosis,
underactive thyroid, herpes simplex of the eye, high blood pressure,
osteoporosis, or stomach ulcer. |
Methylprednisolone
Prednisone |
These steroids are available in pill form or
as an injection into a joint. Improvements are seen in several hours
up to 24 hours after administration. There is potential for serious side
effects, especially at high doses. They are used for severe flares and
when the disease does not respond to NSAIDs and DMARDs. |
Osteoporosis, mood changes, fragile skin, easy
bruising, fluid retention, weight gain, muscle weakness, onset or worsening
of diabetes, cataracts, increased risk of infection, hyper-tension (high
blood pressure). |
Doctor monitoring for continued effectiveness
of medication and for side effects is needed. |
| Disease-modifying antirheumatic drugs
(DMARDs) |
These are common arthritis medications. They
relieve painful, swollen joints and slow joint damage, and several DMARDs
may be used over the disease course. They take a few weeks or months
to have an effect, and may produce significant improvements for many
patients. Exactly how they work is still unknown. |
Side effects vary with each medicine. DMARDs
may increase risk of infection, hair loss, and kidney or liver damage. |
Doctor monitoring allows the risk of toxicities
to be weighed against the potential benefits of individual medications. |
| Azathioprine |
This drug was first used in higher doses in cancer
chemotherapy and organ transplantation. It is used in patients who have
not responded to other drugs, and in combination therapy. |
Cough or hoarseness, fever or chills, loss of
appetite, lower back or side pain, nausea or vomiting, painful or difficult
urination, unusual tiredness or weakness. |
Before taking this drug, tell your doctor if
you use allopurinol or have kidney or liver disease. This drug can reduce
your ability to fight infection, so call your doctor immediately if you
develop chills, fever, or a cough. Regular blood and liver function tests
are needed. |
| Cyclosporine |
This medication was first used in organ transplantation
to prevent rejection. It is used in patients who have not responded to
other drugs. |
Bleeding, tender, or enlarged gums; high blood
pressure; increase in hair growth; kidney problems; trembling and shaking
of hands. |
Before taking this drug, tell your doctor if
you have one of the following: sensitivity to castor oil (if receiving
the drug by injection), liver or kidney disease, active infection, or
high blood pressure. Using this drug may make you more susceptible to
infection and certain cancers. Do not take live vaccines while on this
drug. |
| Hydroxychloroquine |
It may take several months to notice the benefits
of this drug, which include reducing the signs and symptoms of rheumatoid
arthritis. |
Diarrhea, eye problems (rare), headache, loss
of appetite, nausea or vomiting, stomach cramps or pain. |
Doctor monitoring is important, particularly
if you have an allergy to any antimalarial drug or a retinal abnormality. |
| Gold sodium thiomalate |
This was one of the first DMARDs used to treat
rheumatoid arthritis. |
Redness or soreness of tongue; swelling or bleeding
gums; skin rash or itching; ulcers or sores on lips, mouth, or throat;
irritation on tongue. Joint pain may occur for one or two days after
injection. |
Before taking this drug, tell your doctor if
you have any of the following: lupus, skin rash, kidney disease, or colitis.
Periodic urine and blood tests are needed to check for side effects. |
| Leflunomide |
This drug reduces signs and symptoms and slows
structural damage to joints caused by arthritis. |
Bloody or cloudy urine; congestion in chest;
cough; diarrhea; difficult, burning, or painful urination or breathing;
fever; hair loss; headache; heartburn; loss of appetite; nausea and/or
vomiting; skin rash; stomach pain; sneezing; and sore throat. |
Before taking this medication, let your doctor
know if you have one of the following: active infection, liver disease,
known immune deficiency, renal insufficiency, or underlying malignancy.
You will need regular blood tests, including liver function tests. Leflunomide
must not be taken during pregnancy because it may cause birth defects
in humans. |
| Methotrexate |
This drug can be taken by mouth or by injection
and results in rapid improvement (it usually takes 3-6 weeks to begin
working). It appears to be very effective, especially in combination
with infliximab or etanercept. In general, it produces more favorable
long-term responses compared with other DMARDs such as sulfasalazine,
gold sodium thiomalate, and hydroxychloroquine. |
Abdominal discomfort, chest pain, chills, nausea,
mouth sores, painful urination, sore throat, unusual tiredness or weakness. |
Doctor monitoring is important, particularly
if you have an abnormal blood count, liver or lung disease, alcoholism,
immune-system deficiency, or active infection. Methotrexate must not
be taken during pregnancy because it may cause birth defects in humans. |
| Sulfasalazine |
This drug works to reduce the signs and symptoms
of rheumatoid arthritis by suppressing the immune system. |
Abdominal pain, aching joints, diarrhea, headache,
sensitivity to sunlight, loss of appetite, nausea or vomiting, skin rash. |
Doctor monitoring is important, particularly
if you are allergic to sulfa drugs or aspirin, or if you have a kidney,
liver, or blood disease. |
| Biologic Response Modifiers |
These drugs selectively block parts of the immune
system called cytokines. Cytokines play a role in inflammation. Long-term
efficacy and safety are uncertain. |
Increased risk of infection, especially tuberculosis.
Increased risk of pneumonia, and listeriosis (a foodborne illness caused
by the bacterium Listeria monocytogenes). |
It is important to avoid eating undercooked foods
(including unpasteurized cheeses, cold cuts, and hot dogs) because undercooked
food can cause listeriosis for patients taking biologic response modifiers. |
Tumor Necrosis Factor Inhibitors
Etanercept
Infliximab
Adalimumab |
These medications are highly effective for treating
patients with an inadequate response to DMARDs. They may be prescribed
in combination with some DMARDs, particularly methotrexate. Etanercept
requires subcutaneous (beneath the skin) injections two times per week.
Infliximab is taken intravenously (IV) during a 2-hour procedure. It
is administered with methotrexate. Adalimumab requires injections every
2 weeks. Long-term efficacy and safety are uncertain. |
Etanercept: Pain or burning in throat;
redness, itching, pain, and/or swelling at injection site; runny or stuffy
nose.
Infliximab: Abdominal pain, cough, dizziness, fainting, headache,
muscle pain, runny nose, shortness of breath, sore throat, vomiting,
wheezing.
Adalimumab: Redness, rash, swelling, itching, bruising, sinus
infection, headache, nausea. |
Long-term efficacy and safety are uncertain.
Doctor monitoring is important, particularly if you have an active infection,
exposure to tuberculosis, or a central nervous system disorder. Evaluation
for tuberculosis is necessary before treatment begins. |
Interleukin1 Inhibitor
Anakinra |
This medication requires daily injections. Long-term
efficacy and safety are uncertain. |
Redness, swelling, bruising, or pain at the site
of injection; head-ache; upset stomach; diarrhea; runny nose; and stomach
pain. |
Doctor monitoring is required. |
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Over the last several decades, research has greatly increased our
understanding of the immune system, genetics, and biology. This research is
now showing results in several areas important to rheumatoid arthritis. Scientists
are thinking about rheumatoid arthritis in exciting ways that were not possible
even 10 years ago.
The National Institutes of Health (NIH) funds a wide variety of
medical research at its headquarters in Bethesda, Maryland, and at universities
and medical centers across the United States. One of the NIH institutes, the
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS),
is a major supporter of research and research training in rheumatoid arthritis
through grants to individual scientists, Specialized Centers of Research, Multidisciplinary
Clinical Research Centers, and Multipurpose Arthritis and Musculoskeletal Diseases
Centers.
Following are examples of current research directions in rheumatoid
arthritis supported by the Federal Government through the NIAMS and other parts
of the NIH.
Scientists are looking at the immune systems of people with rheumatoid
arthritis and in some animal models of the disease to understand why and how
the disease develops. For example, small studies are looking at the role of
T cells, which play an important role in immunity and in the progression of
rheumatoid arthritis. Findings from these studies may lead to precise, targeted
therapies that could stop the inflammatory process in its earliest stages.
They may even lead to a vaccine that could prevent rheumatoid arthritis.
Researchers are studying genetic factors that predispose some people
to developing rheumatoid arthritis, as well as factors connected with disease
severity. For example, by studying genetically engineered mice, scientists
supported by the NIH discovered that immune cells called mast cells play a
key role in the development of rheumatoid arthritis. Findings from these studies
should increase our understanding of the disease and will help develop new
therapies, as well as guide treatment decisions.
In a major effort aimed at identifying genes involved in rheumatoid
arthritis, the NIH and the Arthritis Foundation have joined together to support
the North American Rheumatoid Arthritis Consortium. This group of 10 research
centers around the United States is collecting medical information and genetic
material from 1,000 families in which two or more siblings have rheumatoid
arthritis. It serves as a national resource for genetic studies of this disease.
To help identify the multiple factors that predict disease course
and outcomes in rheumatoid arthritis in African Americans, the NIH is supporting
the Consortium for the Longitudinal Evaluations of African Americans with Early
Rheumatoid Arthritis (CLEAR) Registry at the University of Alabama at Birmingham.
This registry aims to collect clinical and x-ray data and DNA to help scientists
analyze genetic and nongenetic factors that predict disease course and outcomes
of rheumatoid arthritis.
Scientists are also unearthing the genetic basis of rheumatoid
arthritis by studying rats with a condition that resembles rheumatoid arthritis
in humans. NIAMS researchers have identified several genetic regions that affect
arthritis susceptibility and severity in these animal models of the disease.
These genetic regions are important because they can assist scientists in predicting
the symptoms and severity of rheumatoid arthritis. Replacing malfunctioning
genes with healthy genes (gene transfer) is being tested in mice, and it may
eventually be used in humans to treat rheumatoid arthritis.
Researchers are also uncovering the complex relationships between
the hormonal, nervous, and immune systems in rheumatoid arthritis. For example,
they are exploring whether and how the normal changes in the levels of naturally
produced steroid hormones (such as estrogen and testosterone) during a person's
lifetime may be related to the development, improvement, or flares of the disease.
Scientists also are researching how these systems interact with environmental
and genetic factors. The results of this research may suggest new treatment
strategies.
Scientists are exploring why so many more women than men develop
rheumatoid arthritis. In hopes of finding clues, they are studying female and
male hormones and other differences between women and men.
Scientists are examining why rheumatoid arthritis often improves
during pregnancy. Results of one study suggest that the explanation may be
related to differences in certain special proteins that pass between a mother
and her unborn child. These proteins help the immune system distinguish between
the body's own cells and foreign cells. Such differences, the scientists speculate,
may change the activity of the mother's immune system during pregnancy.
A growing body of evidence indicates that infectious agents, such
as viruses and bacteria, may trigger rheumatoid arthritis in people who have
an inherited predisposition to the disease. Scientists are trying to discover
which infectious agents may be responsible and how they trigger arthritis.
Researchers are searching for new drugs or combinations of drugs
that can reduce inflammation and slow or stop the progression of rheumatoid
arthritis with few side effects. Already, the new biologic response modifiers
infliximab and etanercept are proving to be extremely effective for some people.
Studies show that these treatments are more effective at slowing joint damage
than methotrexate alone. Combination treatment with etanercept and methotrexate
or infliximab and methotrexate has been found even more effective than either
of the new treatments alone. (Methotrexate was used for comparison because
it is a commonly prescribed "front-line" treatment.) The U.S. Food and Drug
Administration recently approved adalimumab (Humira) for slowing the progression
of structural damage in adults with moderate to severe rheumatoid arthritis
who have not responded well to one or more disease modifying antirheumatic
drugs.
Investigators have also shown that treatment of rheumatoid arthritis
with minocycline, a drug in the tetracycline family, has a modest benefit. Other
studies have shown that the omega-3 fatty acids in certain fish or plant seed
oils also may reduce rheumatoid arthritis inflammation. However, many people
are not able to tolerate the large amounts of oil necessary for any benefit.
Scientists are examining many issues related to quality of life
for people with rheumatoid arthritis and the quality, cost, and effectiveness
of the health care services they receive. Some new techniques for managing
symptoms under investigation include tai chi (a form of movement-based meditation),
and cognitive-behavioral therapy (a technique that teaches you to anticipate
and prepare yourself for the situations and bodily sensations that may trigger
painful symptoms). Scientists have found that even a small improvement in a
patient's sense of physical and mental well-being can have an impact on his
or her quality of life and use of health care services.
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Scientists are making rapid progress in understanding the complexities
of rheumatoid arthritis: how and why it develops, why some people get it and
others do not, why some people get it more severely than others. Results from
research are having an impact today, enabling people with rheumatoid arthritis
to remain active in life, family, and work far longer than was possible 20
years ago. There is also hope for tomorrow, as researchers begin to apply new
technologies such as stem cell transplantation and novel imaging techniques.
(Stem cells have the capacity to differentiate into specific cell types, which
gives them the potential to change damaged tissue in which they are placed.)
These and other advances will lead to an improved quality of life for people
with rheumatoid arthritis.
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National
Institute of Arthritis and Musculoskeletal and Skin Diseases
The National
Institute of Allergy and Infectious Diseases
National Center
for Complementary and Alternative Medicine
American Academy of Orthopaedic
Surgeons
American College
of Rheumatology
Arthritis Foundation
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