Rheumatoid Arthritis (RA)

Many people with rheumatoid arthritis have distinctive antibodies in their blood, such as rheumatoid factor and anti-CCP antibodies. However, doctors do not rely only on blood tests to diagnose rheumatoid arthritis.

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.)

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. The presence of anti-CCP and rheumatoid factor, especially in people who smoke cigarettes, predicts that their arthritis will be more severe.

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 Overview of Anemia Anemia is a condition in which the number of red blood cells is low. Red blood cells contain hemoglobin, a protein that enables them to carry oxygen from the lungs and deliver it to all parts... read more (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.

Because disease-modifying antirheumatic drugs Disease-modifying antirheumatic drugs (DMARDs) 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.... read more (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 medications used to treat rheumatoid arthritis, see Medications for Rheumatoid Arthritis Medications for Rheumatoid Arthritis 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.... read more .

Complete bed rest is rarely necessary, even for a short time. However, quality sleep is important, because poor sleep increases pain.

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.

Along with medications to reduce joint inflammation, a treatment plan for rheumatoid arthritis should include nondrug therapies, such as exercise, physical therapy Physical Therapy (PT) Physical therapy, a component of rehabilitation, involves exercising and manipulating the body with an emphasis on the back, upper arms, and legs. It can improve joint and muscle function, helping... read more (which includes massage Massage Professional rehabilitation therapists treat pain and inflammation. Such treatment makes movement easier and enables people to participate more fully in rehabilitation. Techniques used include... read more , traction, and deep heat treatments Heat therapy Professional rehabilitation therapists treat pain and inflammation. Such treatment makes movement easier and enables people to participate more fully in rehabilitation. Techniques used include... read more ), and occupational therapy Occupational Therapy (OT) Occupational therapy, a component of rehabilitation, is intended to enhance a person's ability to do basic self-care activities, useful work, and leisure activities. These activities include... read more (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 Cold therapy (cryotherapy) Professional rehabilitation therapists treat pain and inflammation. Such treatment makes movement easier and enables people to participate more fully in rehabilitation. Techniques used include... read more 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.

If medications 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.

NSAIDs Nonsteroidal Anti-Inflammatory Drugs Pain relievers (analgesics) are the main drugs used to treat pain. Doctors choose a pain reliever based on the type and duration of pain and on the drug's likely benefits and risks. Most pain... read more can be 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 .)

NSAIDs can reduce the swelling in affected joints and relieve pain and stiffness. They can be taken by mouth or applied directly to the skin over painful joints. Rheumatoid arthritis, unlike osteoarthritis, causes considerable inflammation. Thus, medications that decrease inflammation, including NSAIDs, have an important advantage over medications such as acetaminophen that reduce pain but not inflammation. However, NSAIDs should generally not be taken by people who have a history of digestive tract (peptic) ulcers Peptic Ulcer Disease A peptic ulcer is a round or oval sore where the lining of the stomach or duodenum has been eaten away by stomach acid and digestive juices. Peptic ulcers can result from infection with Helicobacter... read more —including stomach ulcers or duodenal ulcers—because NSAIDs can upset the stomach and cause ulcers to bleed. Medications called proton pump inhibitors (such as esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole) can reduce the risk of stomach or duodenal ulcers (see table ).

Other possible side effects of NSAIDs may include headache, confusion, elevation of blood pressure, worsening of kidney function, swelling, and decreased platelet function, causing bruising or bleeding. 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.

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 and do not affect platelet function and cause bruising or bleeding like the other NSAIDs. 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.

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 to have an effect. Even if pain is decreased with NSAIDs, a doctor will likely prescribe a DMARD because the disease may otherwise progress even if symptoms are lessened. (See also table .)

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 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. The liver can scar, but this scarring most often can be detected by monitoring with regular blood tests 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) may occur. Blood counts should be tested about every 2 to 3 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 medication 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 tests, 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 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 medications 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. In males, sulfasalazine may cause a low sperm count, which is reversible.

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. (See also table .)

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

They are also useful in treating rheumatoid 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, thinning and bruising of the skin, glaucoma and other eye problems such as cataracts, and increase the risk of certain infections.

A biologic agent is something made from a living organism, often using cells in a laboratory. 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), and interleukin-6 receptor blockers (tocilizumab and sarilumab). (See also table .)

Biologic agents may suppress the inflammation so that corticosteroids can be avoided or given in lower doses. But by interfering with the immune system, biologic agents may increase the risks of infection and certain cancers. Because treatment with biologic agents increases the risk of infection, before starting treatment with a biologic agent people should be up to date on vaccinations (see table ).

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.

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 Tuberculosis (TB) Tuberculosis is a chronic contagious infection caused by the airborne bacteria Mycobacterium tuberculosis. It usually affects the lungs, but almost any organ can be involved. Tuberculosis... read more and fungal infections Overview of Fungal Infections Fungi are neither plants nor animals. They were once thought to be plants but are now classified as their own kingdom. Some fungi cause infections in people. Because fungal spores are often... read more ), skin cancers other than melanoma, and reactivation of hepatitis B Hepatitis B, Chronic Chronic hepatitis B is inflammation of the liver that is caused by the hepatitis B virus and that has lasted more than 6 months. Most people with chronic hepatitis B have no symptoms, but some... read more .

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, usually as 2 doses given 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. It can cause severe liver damage by reactivating hepatitis B Hepatitis B, Acute Acute hepatitis B is inflammation of the liver that is caused by the hepatitis B virus and that lasts from a few weeks up to 6 months. Hepatitis B is spread through contact with blood or other... read more in people who had previously been infected with this virus.

The COVID-19 vaccine COVID-19 Vaccine Coronavirus disease 2019 (COVID-19) vaccines provide protection against COVID-19. COVID-19 is the disease caused by infection with the SARS-CoV-2 virus. There are multiple COVID-19 vaccines... read more may be less effective in people taking rituximab, and people on rituximab may have poorer outcomes if infected with COVID-19. Therefore, doctors now try to reserve rituximab for people who did not respond to other biologic DMARDs and to those with certain lymphatic disorders and cancers.

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 Tuberculosis (TB) Tuberculosis is a chronic contagious infection caused by the airborne bacteria Mycobacterium tuberculosis. It usually affects the lungs, but almost any organ can be involved. Tuberculosis... read more ), suppression of blood cell production in the bone marrow (neutropenia), anaphylaxis Anaphylactic Reactions Anaphylactic reactions are sudden, widespread, potentially severe and life-threatening allergic reactions. Anaphylactic reactions often begin with a feeling of uneasiness, followed by tingling... read more (a life-threatening allergic reaction), and increased liver enzymes. It is given by vein every 4 weeks. There may be an increased risk when people who have had diverticulitis use tocilizumab.

Janus kinase inhibitors are small molecule agents that interfere with the communication between cells that coordinate inflammation by inhibiting the enzyme JAK. JAK inhibitors include tofacitinib, baricitinib, and upadacitinib. (See also table .) Because treatment with JAK inhibitors increases the risk of infection, including herpes zoster infection, people should be vaccinated against zoster Shingles Vaccine The herpes zoster virus that causes shingles is the same virus that causes chickenpox. After chickenpox resolves, the virus remains in the body. It can be reactivated years later and cause shingles... read more before starting treatment with a JAK inhibitor.

Baricitinib is given to people who have not been helped by or who cannot tolerate TNF antagonists. Baricitinib increases the risk of nonmelanoma skin cancer, high cholesterol levels Dyslipidemia Dyslipidemia is a high level of cholesterol and/or triglycerides or a low level of high-density lipoprotein (HDL) cholesterol. Lifestyle, genetics, disorders (such as low thyroid hormone levels... read more (hypercholesterolemia), and deep vein thrombosis Deep Vein Thrombosis (DVT) Deep vein thrombosis is the formation of blood clots (thrombi) in the deep veins, usually in the legs. Blood clots may form in veins if the vein is injured, a disorder causes the blood to clot... read more (DVT). It is taken by mouth once a day.

Tofacitinib 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 nonmelanoma skin cancer and high cholesterol levels Dyslipidemia Dyslipidemia is a high level of cholesterol and/or triglycerides or a low level of high-density lipoprotein (HDL) cholesterol. Lifestyle, genetics, disorders (such as low thyroid hormone levels... read more . Tofacitinib is taken by mouth twice a day.

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