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Rheumatoid Arthritis (RA)

By

Apostolos Kontzias

, MD, Stony Brook University School of Medicine

Last full review/revision May 2020| Content last modified May 2020
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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, disease-modifying antirheumatic drugs, and immunosuppressive drugs), and sometimes 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. However, the prognosis for juvenile idiopathic arthritis is often somewhat different.

The exact cause of rheumatoid arthritis is not known. It is considered an autoimmune disease. Components of the immune system attack the soft tissue that lines the joints (synovial tissue) 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 (wear away), 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 and cigarette smoking) are thought to play a role.

Symptoms

People with rheumatoid arthritis may have

  • Relatively mild symptoms

  • Occasional flare-ups with long periods of remission (in which the disease is inactive)

  • A severe, 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. Rheumatoid arthritis can affect any joint, but most often the first inflamed are the small joints in the

  • Hands

  • Wrists

  • Fingers

  • Feet

  • Toes

Other commonly affected joints include the

  • Knees

  • Shoulders

  • Elbows

  • Ankles

  • Hips

Rheumatoid arthritis can also affect the neck. The lower spine and the joints at the tips of the fingers are not affected.

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 often tender, warm, and enlarged because of swelling of the soft tissue lining the joint (synovitis) and sometimes fluid within the joint (synovial fluid). Joints can quickly become deformed. Joints may freeze in one position so that they cannot bend or open fully, which leads to a limited range of motion. 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, or may develop other deformities (see swan-neck deformity and boutonnière deformity).

When the Fingers Are Abnormally Bent

Some disorders, such as rheumatoid arthritis, and injuries can cause the fingers to bend abnormally. In swan-neck deformity, the joint at the base of the finger bends in (flexes), the middle joint straightens out (extends), and the outermost joint bends in (flexes). In boutonnière deformity, the middle finger joint is bent inward (toward the palm), and the outermost finger joint is bent outward (away from the palm).

When the Fingers Are Abnormally Bent
Examples of Finger Deformities

Swollen wrists can pinch a nerve and result in numbness or tingling due to 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 just under the skin (called rheumatoid nodules), 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). Vasculitis 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 (lymphadenopathy), Felty syndrome (a low white blood cell count and an enlarged spleen), Sjögren syndrome (dry mouth and eyes), thinning of the white of the eye (sclera), or red, irritated eyes caused by inflammation (episcleritis).

Rheumatoid arthritis can also affect the neck, making the bones unstable and increasing the risk of the bones putting pressure on (compressing) the spinal cord.

Did You Know...

  • Although some people who have rheumatoid arthritis find that specific foods may cause flare-ups, no specific foods have been proved to cause flare-ups.

Diagnosis

  • Blood tests

  • X-rays

  • Examination of joint fluid

In addition to the important characteristic pattern of symptoms, doctors follow established criteria when evaluating a person for rheumatoid arthritis. Doctors suspect people have rheumatoid arthritis if they have more than one joint with definite swelling of the joint's lining that is not caused by another disorder. Doctors diagnose people with rheumatoid arthritis if they have certain combinations of the following criteria:

  • Involvement of the joints that are most typical of rheumatoid arthritis

  • High blood levels of rheumatoid factor, anti-cyclic citrullinated peptide (anti-CCP) antibodies, or both

  • High blood levels of C-reactive protein, a high erythrocyte sedimentation rate (ESR), or both

  • Symptoms that have lasted at least 6 weeks

Doctors do blood tests to determine a person's blood levels of rheumatoid factor and anti-CCP antibodies and usually C-reactive protein, ESR, or both. They also frequently do x-rays of the hands, wrists, and affected joints. X-rays show characteristic changes in the joints caused by rheumatoid arthritis. Magnetic resonance imaging (MRI), another imaging test, detects joint abnormalities at an earlier stage but is not usually needed at first.

Doctors may also insert a needle into a joint to draw a sample of synovial fluid. The fluid is examined to determine whether it is consistent with features of rheumatoid arthritis and to rule out other disorders that cause symptoms similar to rheumatoid arthritis. Synovial fluid needs to be analyzed to establish that a person has rheumatoid arthritis but does not always need to be analyzed whenever a flare-up causes joints to become swollen.

Blood tests

Many people with rheumatoid arthritis have distinctive antibodies in their blood, such as rheumatoid factor and anti-CCP antibodies.

Rheumatoid factor is present in 70% of people with rheumatoid arthritis. (Rheumatoid factor also occurs in several other diseases, such as cancers, systemic lupus erythematosus, hepatitis, and some other infections. Some people without any disorder, particularly older adults, have rheumatoid factor in their blood.) Usually, the higher the level of rheumatoid factor in the blood, the more severe the rheumatoid arthritis and the poorer the prognosis.

Anti-CCP antibodies are present in over 75% of people who have rheumatoid arthritis and are almost always absent in people who do not have rheumatoid arthritis.

C-reactive protein levels are often high in people with rheumatoid arthritis. Levels of C-reactive protein (a protein that circulates in the blood) dramatically increase when there is inflammation. High C-reactive protein levels can mean the disease is active.

The ESR is increased in 90% of people who have active rheumatoid arthritis. The ESR is another test for inflammation and measures the rate at which red blood cells settle to the bottom of a test tube containing blood. However, similar increases in the ESR, C-reactive protein level, or both occur in many other disorders. Doctors may monitor the ESR or C-reactive protein to help determine whether the disease is active.

Most people with rheumatoid arthritis have mild anemia (an insufficient number of red blood cells). 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 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 untreated people develop permanent joint abnormalities within 10 years. Rheumatoid arthritis decreases life expectancy by 3 to 7 years. Heart disease (a risk with rheumatoid arthritis), infection, and gastrointestinal bleeding are the most common complications that cause death. Side effects of drug treatment, cancer, and the underlying disease also may be responsible. Rarely, rheumatoid arthritis resolves spontaneously.

Treatment relieves symptoms in 3 of 4 people. However, at least 10% of people with rheumatoid arthritis 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

  • Being a cigarette smoker

  • Obesity

  • Having a high erythrocyte sedimentation rate (ESR)

  • Having high levels of rheumatoid factor or anti-cyclic citrullinated peptide (anti-CCP) antibodies

Treatment

  • Drugs

  • Lifestyle measures, such as rest, diet, exercise, and stopping smoking

  • Physical therapy and occupational therapy

  • Sometimes surgery

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, adequate nutrition, and physical treatments. People should take measures that decrease their risk of heart disease, such as stopping smoking and getting treated, if necessary, for high blood pressure and high blood lipids or cholesterol.

Drugs

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. For other drugs used to treat rheumatoid arthritis, see Drugs for Rheumatoid Arthritis.

Rest and nutrition

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 nearby muscles from weakening and joints from freezing in place.

A regular, healthy diet is generally appropriate. A diet rich in fish (omega-3 fatty acids) and plant oils but low in red meat can partially relieve symptoms in some people. Some people may have flare-ups after eating certain foods, and if so, these foods should be avoided, but such flare-ups occur rarely. No specific foods have been proved to cause flare-ups. Many diets have been proposed but have not proved helpful. Fad diets should be avoided.

Physical treatments

Along with drugs to reduce joint inflammation, a treatment plan for rheumatoid arthritis should include nondrug therapies, such as exercise, physical therapy (which includes massage, traction, and deep heat treatments), and occupational therapy (which includes self-help devices).

Inflamed joints should be gently stretched so they do not freeze in one position. Heat therapy can be helpful because heat improves muscle function by reducing stiffness and muscle spasm. As the inflammation subsides, regular, active exercises can help, although a person should not exercise to the point of excessive fatigue. For many people, exercise in warm water may be easier.

Treatment of tight joints consists of intensive exercises and occasionally the use of splints to gradually extend the joint. Cold may be applied to reduce pain caused by temporary worsening in one joint.

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 self-help devices such as grippers reduce the need to squeeze the hand forcefully.

Surgery

If drugs have not helped, surgical treatment may be needed. 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.

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 pinch, and unstable vertebrae at the top of the neck can be fused to prevent them from compressing the spinal cord.

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

Replacing All of a Hip (Total Hip Replacement)

Sometimes the whole hip joint must be replaced. The whole hip joint is the top (head) of the thighbone (femur) and the surface of the socket into which the head of the thighbone fits. This procedure is called total hip replacement or total hip arthroplasty. The head of the thighbone is replaced with a ball-shaped part (prosthesis), made of metal. The prosthesis has a strong stem that fits within the center of the thighbone. The socket is replaced with a metal shell lined with durable plastic.

Replacing All of a Hip (Total Hip Replacement)

Replacing a Knee

A knee joint damaged by osteoarthritis may be replaced with an artificial joint. After a general anesthetic is given, the surgeon makes an incision over the damaged knee. The knee cap (patella) may be removed, and the ends of the thigh bone (femur) and shinbone (tibia) are smoothed so that the parts of the artificial joint (prosthesis) can be attached more easily. One part of the artificial joint is inserted into the thigh bone, the other part is inserted into the shinbone, and then the parts are cemented in place.

Replacing a Knee

Drugs for Rheumatoid Arthritis

The main goal of drug treatment is to reduce inflammation and thereby prevent erosions, progression of the disease, and loss of joint function.

The main categories of drugs used to treat rheumatoid arthritis are

Many of these drugs are used in combination. For example, doctors may prescribe two DMARDs together or a corticosteroid plus a DMARD. However, the best combinations of drugs are not yet clear. Typically, biologic agents are not used in combination with other biologic agents because these combinations increase the frequency of infections.

All the categories of drugs have potentially serious side effects that must be looked for during treatment.

Table
icon

Drugs Used to Treat Rheumatoid Arthritis

Drug

Some Side Effects

Comments

Diclofenac

Ibuprofen

Naproxen

Many others

Upset stomach

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.

These drugs are taken by mouth. Some NSAIDs are in cream form and can be applied to the skin directly over painful joints.

Cyclooxygenase-2 (COX-2) inhibitors (coxibs), such as celecoxib

Kidney problems

Increased blood pressure

Less risk of stomach ulcer and bleeding than with other NSAIDs

Possible increased risk of heart attack and stroke

Possible increased risk of bruising and bleeding

Hydroxychloroquine

Usually mild dermatitis (rash)

Muscle aches or weakness

Eye problems

All DMARDs can slow progression of joint damage as well as gradually decrease pain and swelling.

Leflunomide is about as effective as methotrexate.

These drugs are taken by mouth.

Methotrexate may be given by injection under the skin (subcutaneously).

Leflunomide

Rashes

Liver disease

Damage to nerves (neuropathy)

Diarrhea

Hair loss

Methotrexate

Liver disease

Lung inflammation

Nausea

Neutropeniaa

Mouth sores

Decreased sperm numbers and fertility in men

Hair loss

Sulfasalazine

Stomach problems

Neutropeniaa

Breakdown of red blood cells (hemolysis)

Liver problems

Rashes

Prednisone

Prednisolone

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

Prednisone and prednisolone can reduce inflammation quickly.

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

These drugs are usually taken by mouth but can be injected into a muscle (intramuscularly) or a vein (intravenously).

Methylprednisolone acetate

Rarely infection at the injection sites or within the joint

Weakening of tissues if injections are given too frequently for too long

Bleeding into the joint after injection, particularly in people taking anticoagulants (blood thinners)

These drugs are given by injection into a joint.

Triamcinolone acetonide

Triamcinolone hexacetonide

Azathioprine

Cyclosporine

Liver disease

Increased risk of cancer (such as lymphoma and nonmelanoma skin cancers)

Neutropeniaa

Cyclosporine: Impaired kidney function, high blood pressure, diabetes

Azathioprine is about as effective as some DMARDs but is more toxic.

Cyclosporine is about as effective as some DMARDs but has a higher risk of side effects.

These drugs are taken by mouth.

Adalimumabb

Certolizumab pegolb

Etanerceptb

Golimumabb

Infliximabb

Potential risk of reactivation of infection (particularly tuberculosis and fungal infections)

Skin cancers other than melanoma

Reactivation of hepatitis B

Demyelinating neurologic disorders (such as Guillain-Barré syndrome or multiple sclerosis)

These drugs produce a dramatic, prompt response in most people.

They can slow joint damage.

Adalimumab, certolizumab pegol, etanercept, and golimumab are given by injection under the skin (subcutaneously).

Infliximab is given as a series of infusions into a vein.

Abataceptc

Lung problems

Increased susceptibility to infection

Headache

Upper respiratory infection

Sore throat

Nausea

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

It may be given by vein (intravenously) or by injection under the skin (subcutaneously).

Anakinrad

Pain, redness, and itching at injection site

Increased risk of infection

Neutropeniaa

Anakinra is probably less effective than adalimumab, etanercept, and infliximab.

It is given by injection under the skin (subcutaneously).

Baricitinibe

Risk of infection, particularly reactivation of chickenpox and shingles

Nonmelanoma skin cancer

High cholesterol levels (hypercholesterolemia)

Baricitinib is taken by mouth.

Rituximabc

When the drug is being given:

  • Itching at injection site

  • Rashes

  • Back pain

  • High or low blood pressure

  • Fever

After the drug is given:

  • Slightly increased risk of certain infections and possibly cancer

  • Neutropeniaa

  • Reactivation of hepatitis B

Rituximab is used only when people do not improve after taking a tumor necrosis factor inhibitor and methotrexate.

It is given by vein (intravenously).

Sarilumabf

Neutropeniaa (too few infection-fighting white blood cells)

Suppression of platelet production in the bone marrow, sometimes with increased susceptibility to bleeding

Increase of liver enzymes

Sarilumab is given by injection under the skin (subcutaneously).

Tocilizumabf

Infection (such as tuberculosis) may be serious or lead to sepsis

Neutropeniaa

Possibly suppression of platelet production in the bone marrow, sometimes with increased susceptibility to bleeding

Increase of liver enzymes

Rarely perforation of the intestine

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

It may be given by vein (intravenously) or by injection under the skin (subcutaneously).

Tofacitinibe

Risk of infection, particularly reactivation of chickenpox and shingles

Nonmelanoma skin cancer

High cholesterol levels (hypercholesterolemia)

Tofacitinib is used when methotrexate has not been effective enough.

It is taken by mouth.

Upadacitinibe

Risk of infection, particularly reactivation of chickenpox and shingles

Nonmelanoma skin cancer

High cholesterol levels (hypercholesterolemia)

Venous thromboembolism

Upadacitinib is used when methotrexate has not been effective enough.

It is taken by mouth.

a Suppression of blood cell production in the bone marrow can lead to decreased numbers of infection-fighting white blood cells called neutrophils, increasing susceptibility to infection.

b Adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab are tumor necrosis factor (TNF) inhibitors.

c Abatacept and rituximab are other types of biologic agents.

d Anakinra is an interleukin-1 receptor blocker.

e Baricitinib, tofacitinib, and upadacitinib are Janus kinase (JAK) inhibitors.

f Sarilumab and tocilizumab are interleukin-6 receptor blockers.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs 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. (See also table Drugs Used to Treat Rheumatoid Arthritis.)

NSAIDs can reduce the swelling in affected joints and relieve pain. They can be taken by mouth or applied directly to the skin over painful joints. Rheumatoid arthritis, unlike osteoarthritis, causes considerable inflammation. Thus, drugs that decrease inflammation, including NSAIDs, have an important advantage over drugs such as acetaminophen that reduce pain but not inflammation. However, NSAIDs (except cyclooxygenase inhibitors) should not be taken by people who have active digestive tract (peptic) ulcers—including stomach ulcers or duodenal ulcers—because NSAIDs can upset the stomach. Drugs called proton pump inhibitors (such as esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole) can reduce the risk of stomach or duodenal ulcers (see table Drugs Used to Treat Peptic Ulcer Disease).

Other possible side effects of NSAIDs may include headache, confusion, increased blood pressure, worsening of high blood pressure, worsening of kidney function, swelling, and decreased platelet function. People who get hives, inflammation and swelling in the nose, or asthma after they take aspirin 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 is no longer used to treat rheumatoid arthritis because effective doses are often toxic.

The cyclooxygenase (COX-2) inhibitors (coxibs, such as celecoxib) are NSAIDs that act similarly to the other NSAIDs but are slightly less likely to damage the stomach. However, if a person also takes aspirin, 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, hydroxychloroquine, leflunomide, and sulfasalazine, slow the progression of rheumatoid arthritis and are given to nearly all people with rheumatoid arthritis. Doctors typically prescribe these drugs as soon as the diagnosis of rheumatoid arthritis is made. Many take weeks or months to have an effect. 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. (See also table Drugs Used to Treat Rheumatoid Arthritis.)

About two thirds of people improve overall, and complete remissions are becoming more common. 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, sulfasalazine, and methotrexate together are more effective than methotrexate alone or the other two together. Also, combining biologic agents with a DMARD is often more effective than using a single drug or certain combinations of DMARDs. For example, methotrexate can be combined with a TNF inhibitor.

Methotrexate 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 3 to 4 weeks, which is relatively rapid for a DMARD. If a person has liver dysfunction or diabetes and takes methotrexate, frequent doctor visits and blood tests may be warranted so that possible side effects can be detected early. The liver can scar, but this scarring 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) occurs. Blood counts should be tested about every 2 months in all people taking the drug. Inflammation of the lung (pneumonitis) is rare. Inflammation in the mouth and nausea can also develop. Severe relapses of arthritis can occur after methotrexate is discontinued. Folate (folic acid) tablets may decrease some of the side effects, such as mouth ulcers. Rheumatoid nodules may enlarge with methotrexate therapy.

Hydroxychloroquine 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 must have their eyes checked by an ophthalmologist before treatment begins and every 12 months during treatment. If the drug has not helped after 9 months, it is discontinued. Otherwise, hydroxychloroquine can be continued as long as necessary.

Leflunomide is taken daily by mouth and has benefits that are similar to those of methotrexate but it is less likely to cause suppression of blood cell production in the bone marrow, abnormal liver function, or inflammation of the lungs (pneumonitis). It can be given at the same time as methotrexate. The major side effects are rashes, liver dysfunction, hair loss, diarrhea, and rarely nerve damage (neuropathy).

Sulfasalazine is initially given nightly by mouth and can relieve symptoms and slow the development of joint damage. Sulfasalazine 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. Because sulfasalazine may quickly cause a person's white blood cell count to become very low (neutropenia), blood tests are done after the first 2 weeks and then about every 12 weeks while the person is taking the drug. Like the other DMARDs, it can cause stomach upset, diarrhea, liver problems, blood cell disorders, and rashes.

Gold compounds are not used anymore.

Corticosteroids

Corticosteroids are potent anti-inflammatory drugs that suppress the immune system. Corticosteroids, such as prednisone, are the most dramatically effective drugs for reducing inflammation and symptoms of rheumatoid arthritis anywhere in the body. Although corticosteroids are effective for short-term use, they may not prevent joint destruction and may become less effective over time, and rheumatoid arthritis is usually active for years. (See also table Drugs Used to Treat Rheumatoid Arthritis.)

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 (see Corticosteroids: Uses and Side Effects). Consequently, doctors usually reserve corticosteroids for short-term use in the following situations:

  • When beginning treatment for severe symptoms (until a DMARD has taken effect)

  • 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 corticosteroids are injected into a joint, the person does not get the same side effects as when taking a corticosteroid by mouth (orally) or vein (intravenously). Corticosteroids can be injected directly into affected joints for fast, short-term relief of pain and swelling.

When used for a long time, corticosteroids may cause weight gain, high blood pressure, diabetes, glaucoma and other eye problems such as cataracts, and increase the risk of certain infections.

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 lifesaving.

Corticosteroids can be

  • Given by vein (intravenously—especially in emergency situations)

  • Taken by mouth (orally)

  • Directly applied to the inflamed area (topically; for example, as eye drops or as skin creams)

  • Inhaled (as in inhaled versions for the lungs, used to treat disorders such as asthma and COPD)

  • Injected into a muscle (intramuscularly)

  • Injected into a joint

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. They can be injected into joints inflamed by rheumatoid arthritis or another disorder.

Corticosteroids are prepared synthetically to have the same action as cortisol (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, and most are longer acting. Corticosteroids are chemically related to, but have different effects than, anabolic steroids (such as testosterone) that are produced by the body and sometimes abused by athletes.

Examples of corticosteroids are prednisone, dexamethasone, triamcinolone, betamethasone, beclomethasone, flunisolide, and fluticasone. All of these drugs are very strong (although strength depends on the dose used). Hydrocortisone is a milder corticosteroid that is available in over-the-counter skin creams.

Corticosteroids reduce the body’s ability to fight infections by reducing inflammation, typically when they are taken by mouth or given by vein. Because of this side effect, they are used with extreme care when infections are present. Oral and intravenous use may cause or 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 stopped abruptly. This is because corticosteroids inhibit the production of cortisol 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. Inhaled corticosteroids and corticosteroids that are applied directly to the skin have far fewer side effects than corticosteroids given by mouth, vein, or injection.

Immunosuppressive drugs

Immunosuppressive drugs weaken (suppress) the immune system and help keep it from attacking the body's own tissues. Each of these potent 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 azathioprine and cyclosporine. (See also table Drugs Used to Treat Rheumatoid Arthritis.)

Azathioprine and cyclosporine are effective in treating severe rheumatoid arthritis. They suppress the inflammation so that corticosteroids can be avoided or given in lower doses. They are taken by mouth once or twice a day. Azathioprine and cyclosporine are about as effective as some DMARDs, but 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 (neutropenia), and an increased risk of some cancers. Additionally, cyclosporine can cause impaired kidney function, high blood pressure, gout, and diabetes. In women who are considering pregnancy, immunosuppressive drugs should be used only after discussion with a doctor.

Biologic agents

Other classes of immunosuppressive drugs are often collectively called biologic agents. A biologic agent is something made from a living organism. Many biologic agents used to treat rheumatoid arthritis are antibodies. Biologic agents used to treat rheumatoid arthritis include abatacept, rituximab, tumor necrosis factor (TNF)–inhibiting drugs (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab), an interleukin-1 receptor blocker (anakinra), interleukin-6 receptor blockers (tocilizumab and sarilumab), and Janus kinase inhibitors (tofacitinib, baricitinib, and upadacitinib). Other JAK inhibitors that may soon become available in the United States include filgotinib and peficitinib. (See also table Drugs Used to Treat Rheumatoid Arthritis.)

Like immunosuppressive drugs, biologic agents may suppress the inflammation so that corticosteroids can be avoided or given in lower doses. Thus, by interfering with the immune system, biologic agents may increase the risks of infection and certain cancers.

Etanercept, infliximab, golimumab, certolizumab pegol, and adalimumab are TNF inhibitors and can be dramatically effective for people who do not respond sufficiently to methotrexate alone.

  • Etanercept is given once a week by injection under the skin.

  • Infliximab is given by vein. After the first dose of infliximab is given, the next two doses are given at 2 and at 6 weeks. Then infliximab is given every 8 weeks.

  • Golimumab is given by injection under the skin once every 4 weeks.

  • Certolizumab pegol is given by injection under the skin. After the first dose, the next two doses are given at 2 and at 4 weeks. Then the drug is given at 2-week or 4-week intervals, depending on the dose.

  • Adalimumab is injected under the skin once every 1 to 2 weeks.

TNF is an important part of the body’s immune system, so inhibition of TNF can impair the body’s ability to fight infections, particularly a reactivated tuberculosis infection. These drugs should be avoided in people who have active infections and should be discontinued before major surgery. Etanercept, infliximab, and adalimumab can be and are often used with methotrexate. People who have severe heart failure should not take high doses of infliximab.

Side effects of TNF inhibitors include the potential risk of reactivation of infection (particularly tuberculosis and fungal infections), skin cancers other than melanoma, and reactivation of hepatitis B.

Anakinra is an interleukin-1 (IL-1) receptor blocker, which means it interrupts one of the major chemical pathways involved in inflammation. Anakinra is given as a single daily injection under the skin. 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. It is prescribed less often because it must be given every day.

Rituximab is a biologic agent that decreases the number of B-cell lymphocytes, one of the white blood cells responsible for causing inflammation and for fighting infection. Rituximab is usually reserved for people who do not improve enough after taking methotrexate 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 can cause effects while it is being given, such as rashes, nausea, back pain, itching, and high or low blood pressure.

Abatacept is another biologic agent that interferes with the communication between cells that coordinates inflammation. Side effects include lung problems, headache, increased susceptibility to infection, and upper respiratory infection. The first injection in the vein takes over 30 minutes to complete. After that, it is injected in a vein or under the skin at 2 weeks and at 4 weeks after the first dose and every 4 weeks thereafter.

Sarilumab is an IL-6 receptor blocker, which means it interrupts one of the major chemical pathways involved in inflammation. This drug is given to people who have not been helped by or who cannot tolerate DMARDs. Sarilumab causes suppression of blood cell production in the bone marrow (neutropenia), suppression of platelet production in the bone marrow (sometimes with increased susceptibility to bleeding), and increased liver enzymes. It is given by injection under the skin (subcutaneously) once every 2 weeks.

Tocilizumab also is an IL-6 receptor blocker. It is often used to treat people who are also taking methotrexate. Side effects include infection (such as tuberculosis), suppression of blood cell production in the bone marrow (neutropenia), anaphylaxis (a life-threatening allergic reaction), and increased liver enzymes. It is given by vein every 4 weeks.

Baricitinib is a Janus kinase (JAK) inhibitor that interferes with the communication between cells that coordinates inflammation by inhibiting an enzyme (Janus kinase, or JAK). This drug is given to people who have not been helped by or who cannot tolerate TNF antagonists. Baricitinib increases the risk of infection (particularly reactivation of chickenpox, causing shingles), skin cancer, high cholesterol levels (hypercholesterolemia), and deep vein thrombosis (DVT). It is taken by mouth once daily.

Tofacitinib also is a JAK inhibitor. This drug is used if a person has taken methotrexate and has not improved enough. Tofacitinib can be used at the same time as methotrexate. Side effects include a risk of infection (particularly reactivation of chickenpox), nonmelanoma skin cancer, and high cholesterol levels (hypercholesterolemia). Tofacitinib is taken by mouth twice daily.

Upadacitinib is a newer JAK inhibitor given to adults with moderately to severely active rheumatoid arthritis when methotrexate has not been effective enough.

More Information

Drugs Mentioned In This Article

Generic Name Select Brand Names
CIMZIA
MEDROL
PLAQUENIL
BECONASE
CORTEF, SOLU-CORTEF
AZULFIDINE
CELESTONE SOLUSPAN, DIPROLENE, LUXIQ
KENALOG
TYLENOL
OZURDEX
DELATESTRYL
IMURAN
NEXIUM
PROTONIX
PREVACID
NEORAL, SANDIMMUNE
ORAPRED, PRELONE
OTREXUP
CUTIVATE, FLONASE
ACIPHEX
ARAVA
AEROSPAN HFA
ACTEMRA
XELJANZ
Baricitinib
CATAFLAM, VOLTAREN
HUMIRA
ENBREL
PRILOSEC
REMICADE
RAYOS
ADVIL, MOTRIN IB
RITUXAN
Sarilumab
CELEBREX
ORENCIA
SIMPONI
KINERET
ALEVE, NAPROSYN
No US brand name
NOTE: This is the Consumer Version. DOCTORS: Click here for the Professional Version
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