PJW Venables, MA, MB BChir, MD, FRCP
James R O’Dell, MD
Paul L Romain, MD
RHEUMATOID ARTHRITIS OVERVIEW — Rheumatoid arthritis (RA) is a chronic inflammatory condition affecting the joints. The condition can also affect other tissues throughout the body. The specific causes of rheumatoid arthritis are unknown.
Rheumatoid arthritis symptoms develop gradually, and it is not always possible to know when the disease first developed. Many people have symptoms that are present continuously, some have symptoms that completely resolve, and others have alternating periods of bothersome symptoms and complete resolution. The onset, severity, and specific symptoms of this condition can vary greatly from person to person.
Treatment plays a key role in controlling the inflammation of rheumatoid arthritis and minimizing joint damage. Treatment usually entails a combination of drug therapy and other non-drug therapies. In some cases, treatment may also involve surgery.
The treatment of rheumatoid arthritis must be tailored to each patient’s individual case, including the severity of the condition, the effectiveness of specific therapies, and the occurrence of any side effects. Treatment choices may be different for a person with rheumatoid arthritis who has other illnesses, especially those of the liver or kidneys. It is important to work with a healthcare provider to create an effective and acceptable plan for treating rheumatoid arthritis.
This topic review discusses the medical treatments that are used for patients with rheumatoid arthritis. A number of other topics about rheumatoid arthritis are available separately. (See “Patient information: Rheumatoid arthritis symptoms and diagnosis” and “Patient information: Disease modifying antirheumatic drugs (DMARDs)” and “Patient information: Rheumatoid arthritis and pregnancy” and “Patient information: Complementary therapies for rheumatoid arthritis”.)
GENERAL PRINCIPLES OF RHEUMATOID ARTHRITIS TREATMENT — The aim of rheumatoid arthritis treatment is to control a patient’s signs and symptoms, to prevent joint damage, and to maintain the patient’s quality of life and ability to function . Joint damage caused by rheumatoid arthritis generally occurs within the first two years of diagnosis, and it is difficult to predict which individuals will develop long-term complications. Therefore, the initial treatment of RA aims to eliminate or minimize inflammation. However, the risk of side effects from treatment must be weighed against the benefits. Treatments that can potentially stop joint damage are generally recommended for all patients with rheumatoid arthritis. (See “General principles of management of rheumatoid arthritis”.)
Long-term medical care with regularly scheduled visits is essential for the successful treatment of rheumatoid arthritis. This care often entails medical visits and tests to assess the effectiveness of treatment and monitor for side effects.
GENERAL MEASURES — Nonpharmacologic therapies include treatments other than medications and are the foundation of treatment for all people with rheumatoid arthritis. There are a wide variety of nonpharmacologic therapies available.
Education and counseling — Education and counseling can help you to better understand the nature of rheumatoid arthritis and cope with the challenges of this condition. You and your healthcare providers can work together to formulate a long-term treatment plan, define reasonable expectations, and evaluate both standard and alternative treatment options.
Nonpharmacologic measures such as biofeedback and cognitive behavioral therapy may help in controlling rheumatoid arthritis symptoms. These measures can reduce pain and disability and improve self-esteem. Programs on topics such as self-management skills, social support, biofeedback, and psychotherapy are offered by the Arthritis Foundation and by many hospitals and clinics (www.arthritis.org/communities/Chapters/ChapDirectory.asp). These programs have been shown to reduce pain, depression, and disability in people with arthritis and to allow them to gain some control over their illness.
Rest — Fatigue is a common symptom of rheumatoid arthritis. Inflamed joints should be rested, but physical fitness should be maintained as much as possible. Several studies have shown that physical fitness improved the quality of sleep, which in turn helps with fatigue. The advice of physical and occupational therapists should be sought for help with fitness programs, if joint pain or limited joint motion interferes with exercise activities.
Exercise — Pain and stiffness often prompt people with rheumatoid arthritis to become inactive. Unfortunately, inactivity can lead to a loss of joint motion, contractions, and a loss of muscle strength. Weakness, in turn, decreases joint stability and further increases fatigue.
Regular exercise can help prevent and reverse these effects . Several different kinds of exercise can be beneficial, including range-of-motion exercises to preserve and restore joint motion, exercises to increase strength (isometric, isotonic, and isokinetic exercises), and exercises to increase endurance (walking, swimming, and cycling).
Exercise programs for people with rheumatoid arthritis should be designed by a physical therapist and tailored to the severity of your condition, your build, and your former activity level. A separate article discusses exercise and arthritis. (See “Patient information: Arthritis and exercise”.)
Physical therapy — Physical therapy can relieve pain, reduce inflammation, and help preserve joint structure and function for patients with rheumatoid arthritis.
Specific types of physical therapy are used to address specific effects of rheumatoid arthritis:
- The application of heat or cold can relieve pain or stiffness
- Ultrasound may reduce inflammation of the sheaths surrounding tendons (tenosynovitis)
- Passive and active exercises can improve and maintain range of motion of the joints
- Rest and rest splinting can reduce joint pain and improve joint function
- Finger splinting can prevent deformities and improve hand function
- Relaxation techniques can relieve secondary muscle spasm
Physical therapy may also include a consultation with a podiatrist who can make foot orthotics (devices that ensure correct position of the foot) and supportive footwear.
Nutrition and dietary therapy — People with active rheumatoid arthritis sometimes lose their appetite or are unable to eat an adequate amount of food. Dietary therapy helps to ensure that you eat an adequate amount of calories and nutrients. However, weight loss may be recommended for overweight and obese people to reduce stress on inflamed joints. (See “Patient information: Weight loss treatments”.)
People with rheumatoid arthritis have a higher risk of developing coronary artery disease. High blood cholesterol is one risk factor for coronary disease that can respond to changes in diet. A nutritionist can recommend specific foods to eat or avoid to achieve a desirable cholesterol level. (See “Patient information: High cholesterol and lipids (hyperlipidemia)”.)
Changes in diet have been investigated as treatments for rheumatoid arthritis. The addition of fish oils and some plant oils, such as borage seed oil, have modestly improved arthritis pain and joint swelling. However, there is no diet that can cure rheumatoid arthritis. No herbal or nutritional supplements, such as cartilage or collagen, can cure rheumatoid arthritis; these treatments can be dangerous and are not usually recommended. (See “Patient information: Complementary therapies for rheumatoid arthritis”.)
Smoking and alcohol — Several different studies have shown that smoking is a risk factor for rheumatoid arthritis and that quitting smoking can improve disease. People who smoke need to quit completely. Assistance in quitting should be obtained, if needed. Moderate alcohol consumption is not harmful to rheumatoid arthritis, although it may increase the risk of liver damage from some drugs such as methotrexate. People should discuss the safety of alcohol use with their doctor, because recommendations depend on the medications a person is taking and their other medical conditions. (See “Patient information: Quitting smoking”.)
Measures to reduce bone loss — Rheumatoid arthritis causes bone loss, which can lead to osteoporosis. Bone loss is more likely in people who are inactive. The use of glucocorticoids, such as prednisone, further increases the risk of bone loss, especially in postmenopausal women. (See “Patient information: Bone density testing”.)
Several measures can minimize the bone loss associated with steroid therapy :
- Use the lowest possible dose of glucocorticoids for the shortest possible time, when possible, to minimize bone loss.
- Consume an adequate amount of calcium and vitamin D, either in the diet or by taking supplements. (See “Patient information: Calcium and vitamin D for bone health”.)
- Use medications that can reduce bone loss, including that which is caused by glucocorticoids. (See “Patient information: Osteoporosis prevention and treatment”.)
RHEUMATOID ARTHRITIS MEDICATIONS — Medications are the cornerstone of treatment for active rheumatoid arthritis. The goals of treatment with rheumatoid arthritis medications are to achieve remission and prevent further damage of the joints and loss of function, without causing permanent or unacceptable side effects.
The type and intensity of rheumatoid arthritis treatment with medication depends upon individual factors and potential drug side effects. In most cases, the dose of a medication is increased until inflammation is suppressed or drug side effects become unacceptable.
The challenge of using medications is to balance the side effects against the need to control inflammation. All patients with rheumatoid arthritis who use medications need regular medical care and blood tests to monitor for complications. If side effects occur, they can often be minimized or eliminated by reducing the dose or switching to a different drug.
Several classes of drugs are used to treat rheumatoid arthritis: nonsteroidal antiinflammatory drugs (NSAIDs), disease modifying antirheumatic drugs (DMARDs) (which includes both traditional DMARDs and biologic agents), glucocorticoids, and, if needed, pain medications.
Nonsteroidal antiinflammatory drugs — Nonsteroidal antiinflammatory drugs (NSAIDs) may be recommended to relieve pain and reduce minor inflammation. However, NSAIDs do not reduce the long-term damaging effects of rheumatoid arthritis on the joints.
NSAIDs must be taken continuously and at a specific dose to have an antiinflammatory effect. Even at the correct doses, NSAIDs must usually be taken for several weeks before their effectiveness is known. If the initial dose of NSAIDs does not improve symptoms, a clinician may recommend increasing the dose gradually or switching to another NSAID. You should not take two NSAIDs at the same time.
Many NSAIDS have significant side effects, including gastrointestinal bleeding, fluid retention, and an increased risk of heart disease. The risks need to weighed carefully against the benefit when taking these drugs.
More detailed information about NSAIDs is available separately. (See “Patient information: Nonsteroidal antiinflammatory drugs (NSAIDs)”.)
Disease-modifying antirheumatic drugs — Disease-modifying antirheumatic drugs (DMARDs) can substantially reduce the inflammation of rheumatoid arthritis, reduce or prevent joint damage, preserve joint structure and function, and enable a person to continue his or her daily activities. Although some DMARDs act slowly, they may allow you to take a lower dose of glucocorticoids to control pain and inflammation.
Drugs in this class include methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide. Detailed information about these medications is available in a separate topic review. (See “Patient information: Disease modifying antirheumatic drugs (DMARDs)”.)
An improvement in symptoms may require four to six weeks of treatment with methotrexate, one to two months of treatment with sulfasalazine, and two to three months of treatment with hydroxychloroquine. Even longer durations of treatment may be needed to derive the full benefits of these drugs. (See “Use of methotrexate in the treatment of rheumatoid arthritis”.)
Biologic agents — Biologic agents, also known as biologics, are disease-modifying antirheumatic drugs (DMARDs) that were designed to prevent or reduce the inflammation that damages joints. Biologics target molecules on cells of the immune system, joints, and the products that are secreted in the joints, all of which can cause inflammation and joint destruction. There are several types of biologics, each of which targets a specific type of molecule involved in this process. (See “Overview of biologic agents in the rheumatic diseases”.)
Biologics are often reserved for people who have not completely responded to DMARDs and for those who cannot tolerate DMARDs in doses large enough to control inflammation.
Biologics that bind tumor necrosis factor (TNF) include etanercept, adalimumab, infliximab, certolizumab pegol, and golimumab. These are called anti-TNF agents or TNF inhibitors. There are additional biologics that target other molecules instead of TNF. These are usually used for people with arthritis that is not well controlled with methotrexate and one of the anti-TNF agents.
Unlike DMARDs, which can take a month or more to begin working, biologics tend to work rapidly, within two weeks for some medications, and within four to six weeks for others. Biologics may be used alone or in combination with other DMARDs (eg, methotrexate), NSAIDs, and/or glucocorticoids (steroids).
All biologic agents must be injected. Some can be injected under the skin by the patient, a family member, or nurse; there are others that must be injected into a vein, which is typically done in a doctor’s office or clinic; this takes between one and three hours to complete.
Side effects — Biologic agents interfere with the immune system’s ability to fight infection and should not be used in people with serious infections.
Testing for tuberculosis (TB) is necessary before starting anti-TNF therapy. People who have evidence of prior TB infection should be treated because there is an increased risk of developing active TB while receiving anti-TNF therapy. (See “Patient information: Tuberculosis”.)
Anti-TNF agents are not recommended for people who have lymphoma or have been treated for lymphoma in the past; people with rheumatoid arthritis, especially those with severe disease, have an increased risk of lymphoma regardless of what treatment is used. Anti-TNF agents have been associated with a further increase in the risk of lymphoma in some studies but not others; more research is needed to define this risk.
Steroids (glucocorticoids) — Glucocorticoids, also called steroids, have strong antiinflammatory effects. Drugs in this class include prednisone and prednisolone. Glucocorticoids may be taken by mouth, injected into a vein, or injected directly into a joint. Glucocorticoids quickly improve symptoms of rheumatoid arthritis such as pain and stiffness, and also decrease joint swelling and tenderness.
Glucocorticoids are generally used to treat rheumatoid arthritis that severely limits a person’s ability to function normally. For such people, glucocorticoid treatment may help control symptoms and preserve function until other slower-acting drugs with greater ability to prevent joint damage, begin to work. They may also be used to treat flares of disease, while a person is receiving other treatments.
Side effects — Steroids have many possible side effects, including weight gain, worsening diabetes, promotion of cataracts in the eyes, thinning of bones (osteopenia and osteoporosis), and an increased risk of infection. Thus, when steroids are used, the goal is to use the lowest possible dose for the shortest period of time.
Pain relievers — Pain relievers relieve pain, but they have no effect on inflammation. Drugs in this class include acetaminophen, tramadol and capsaicin cream or ointment. Use of narcotics like codeine, oxycodone, and hydrocodone, is generally discouraged because they also have no effect on inflammation, and because of the long-term nature of rheumatoid arthritis and the risk of dependence and addiction.
However, people with a badly damaged joint who cannot undergo joint replacement surgery may benefit from use of a long-acting narcotic under the supervision of a rheumatologist or pain specialist.
Treatment of flares — Flares are temporary exacerbations of rheumatoid arthritis that can occur in addition to the ongoing inflammation. In people who are already taking methotrexate or oral steroids, flares can often be controlled by increasing the doses of these drugs. Alternatively, flares can be controlled by steroids that are given by injection. Rest is often helpful during flares; hospitalization is rarely necessary.
Which rheumatoid arthritis treatment will I get? — The type of drugs that your doctor recommends will depend on how severe your arthritis is and how well you respond to the medications. If you have early, mild arthritis, your treatment may be different from someone who has more severe arthritis or whose arthritis persists despite initial treatment efforts. In general, nearly all patients with rheumatoid arthritis will receive a disease modifying antirheumatic drug (DMARD) as part of their treatment program. A different DMARD, whether one of the traditional DMARDs or a biologic agent, will be used either instead of or in addition to the initial drug, if the treatment used is judged to be inadequate. (See “General principles of management of rheumatoid arthritis” and “Treatment of early, mildly active rheumatoid arthritis in adults” and “Treatment of early, moderately active rheumatoid arthritis in adults” and “Treatment of early, severely active rheumatoid arthritis in adults” and “Treatment of persistently active rheumatoid arthritis in adults”.)
SURGERY — A person with end-stage rheumatoid arthritis has little or no evidence of ongoing inflammation but often has significant joint damage with deformity and loss of joint function. End-stage rheumatoid arthritis treatment includes therapies that reduce pain and slow or prevent additional changes in joint structure and function.
Patients with end-stage rheumatoid arthritis may have pain due to joint damage rather than from inflammation. In this case, surgery may be recommended to replace a damaged joint. (See “Patient information: Total hip replacement (arthroplasty)” and “Patient information: Total knee replacement (arthroplasty)”.)
However, some joints cannot be successfully replaced. For such joints, a surgical fusion may be recommended to limit movements that cause pain.
Pregnancy — Treatment of rheumatoid arthritis during pregnancy is discussed in detail in a separate topic review. (See “Patient information: Rheumatoid arthritis and pregnancy”.)
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed every four months on our Web site (www.uptodate.com/patients).
Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient Level Information:
Patient information: Rheumatoid arthritis symptoms and diagnosis
Patient information: Disease modifying antirheumatic drugs (DMARDs)
Patient information: Rheumatoid arthritis and pregnancy
Patient information: Complementary therapies for rheumatoid arthritis
Patient information: Arthritis and exercise
Patient information: Weight loss treatments
Patient information: High cholesterol and lipids (hyperlipidemia)
Patient information: Bone density testing
Patient information: Calcium and vitamin D for bone health
Patient information: Osteoporosis prevention and treatment
Patient information: Nonsteroidal antiinflammatory drugs (NSAIDs)
Patient information: Tuberculosis
Patient information: Total hip replacement (arthroplasty)
Patient information: Total knee replacement (arthroplasty)
Patient information: Quitting smoking
Professional Level Information:
Assessment of rheumatoid arthritis activity in clinical trials and clinical practice
Cervical subluxation in rheumatoid arthritis
Clinical features of rheumatoid arthritis
Polyarticular onset juvenile idiopathic arthritis: Clinical manifestations and diagnosis
Clinically useful biologic markers in the diagnosis and assessment of outcome in rheumatoid arthritis
Diagnosis and differential diagnosis of rheumatoid arthritis
Disease outcome and functional capacity in rheumatoid arthritis
Epidemiology, risk factors for, and possible causes of rheumatoid arthritis
Evaluation and medical management of end-stage rheumatoid arthritis
General principles of management of rheumatoid arthritis
Interstitial lung disease in rheumatoid arthritis
Leflunomide in the treatment of rheumatoid arthritis
Polyarticular onset juvenile idiopathic arthritis: Management
Miscellaneous novel therapies in rheumatoid arthritis
Ocular manifestations of rheumatoid arthritis
Overview of the systemic and nonarticular manifestations of rheumatoid arthritis
Randomized clinical trials in rheumatoid arthritis of biologic agents that inhibit IL-1, IL-6, and RANKL
Renal disease in patients with rheumatoid arthritis
Rheumatoid arthritis and pregnancy
Rituximab and other B cell targeted therapies for rheumatoid arthritis
Sulfasalazine in the treatment of rheumatoid arthritis
T cell targeted therapies for rheumatoid arthritis
Total joint replacement for severe rheumatoid arthritis
Treatment of early, mildly active rheumatoid arthritis in adults
Treatment of early, moderately active rheumatoid arthritis in adults
Treatment of early, severely active rheumatoid arthritis in adults
Treatment of persistently active rheumatoid arthritis in adults
Use of glucocorticoids in the treatment of rheumatoid arthritis
Use of methotrexate in the treatment of rheumatoid arthritis
Overview of biologic agents in the rheumatic diseases
The following organizations also provide reliable health information:
- National Library of Medicine
(www.nlm.nih.gov/medlineplus/arthritis.html, available in Spanish)
- American College of Rheumatology
- The Arthritis Foundation
Patient support — There are a number of online forums where patients can find information and support from other people with similar conditions.
- About.com Arthritis Forum
- American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 Update. Arthritis Rheum 2002; 46:328.
- Van Den Ende CH, Vliet Vlieland TP, Munneke M, Hazes JM. Dynamic exercise therapy for rheumatoid arthritis. Cochrane Database Syst Rev 2000; :CD000322.
- Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Arthritis Rheum 2001; 44:1496.
- Geusens P, Wouters C, Nijs J, et al. Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. A 12-month, double-blind, controlled study. Arthritis Rheum 1994; 37:824.