Patient information: Rheumatoid arthritis treatment

RHEUMATOID ARTHRITIS OVERVIEW

Rheumatoid arthritis (RA) is a chronic inflammatory condition. The condition can affect many tissues throughout the body, but the joints are usually most severely affected. The specific causes of rheumatoid arthritis are unknown.

Rheumatoid arthritis symptoms develop gradually, and it is not always possible to know when it first developed. Many people have symptoms that are present continuously, some have symptoms which 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 in a particular individual must be tailored to their particular 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 traditional 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, and to maintain their quality of life and ability to function [1]. 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.

INITIAL TREATMENT OF RHEUMATOID ARTHRITIS

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 can be very effective for 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. Resting inflamed joints by taking naps often helps restore energy. You can alternate rest with activity, when possible.

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 [2]. Several different kinds of exercises 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 in joint swelling in one study [3]. However, there is no diet that can cure rheumatoid arthritis. No herbal or nutritional supplements, such as cartilage and collagen, can cure rheumatoid arthritis; these treatments can be dangerous and are not usually recommended. (See "Patient information: Complementary therapies for rheumatoid arthritis".)

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 [4]:

• Use the lowest possible dose of glucocorticoids for the shortest possible time, when possible, to minimize bone loss.
• Consume an adequate amount of calcium (1000 to 1500 mg/day) and vitamin D (400 to 800 IU/day), either in the diet or by taking supplements. (See "Patient information: Calcium and vitamin D for bone health".)

• Medications called bisphosphonates, such as alendronate (Fosamax®), risedronate (Actonel®), ibandronate (Boniva®) and etidronate (Didronel®), can reduce bone loss. Use of calcitonin in the form of a nasal spray (Miacalcin®) can also reduce bone loss 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: Non-steroidal antiinflammatory drugs (NSAIDs), disease modifying antirheumatic drugs (DMARDs), biologic response modifiers, glucocorticoids, and if needed, analgesics.

Nonsteroidal anti-inflammatory drugs — Nonsteroidal anti-inflammatory 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 anti-inflammatory effect (table 1). Even at the correct doses, NSAIDs must usually be taken for two to four 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 DMARDs act slowly, they may allow you to take a lower dose of glucocorticoids to control pain and inflammation.

Drugs in this class include hydroxychloroquine (Plaquenil®), methotrexate (Rheumatrex®), gold salts (Ridaura®, Solganal®), D-penicillamine (Depen®, Cuprimine®), sulfasalazine (Azulfidine®), azathioprine (Imuran®), leflunomide (Arava®), and cyclosporine (Sandimmune®, Neoral®). 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".)

Minocycline — In some people with early rheumatoid arthritis, taking an antibiotic (minocycline) may have some benefit. This treatment may be a reasonable alternative to hydroxychloroquine and sulfasalazine.

Biologic response modifiers — Biologic response modifiers, also known as biologics, are medications that were designed to prevent or reduce the inflammation that damages joints. Biologics target molecules on cells of the immune system, joint, and the products that are secreted in the joint, 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 (tumor necrosis factor, interleukin-1, and cell surface molecules on T and B lymphocytes). (See "Overview of biologic agents in the rheumatic diseases".)

• Biologics that bind tumor necrosis factor (TNF), called anti-TNF treatments, include Etanercept (Enbrel®), adalimumab (Humira®), and infliximab (Remicade®). These are called anti-TNF agents.
• Anakinra (Kineret®) inhibits interleukin-1. Anakinra is significantly less potent than TNF inhibitors in most people with rheumatoid arthritis. It is occasionally recommended for selected individuals who do not respond to anti-TNF agents. Anakinra cannot be used at the same time as anti-TNF agents due to the risk of infection.
• Abatacept (Orencia®) interferes with the activation of T cells. Abatacept is usually recommended only for people with moderate or severe rheumatoid arthritis that is not controlled with methotrexate and an anti-TNF agent. (See "T cell targeted therapies for rheumatoid arthritis".)

• Rituximab (Rituxan®) depletes B cells. Rituximab is usually recommended only for people with moderate or severe rheumatoid arthritis that is not controlled with methotrexate and an anti-TNF agent. (See "Rituximab and other B cell targeted therapies for rheumatoid arthritis".)

Unlike DMARDs, which can take a month or more to begin working, biologics work rapidly, within two weeks for some medications (Enbrel®, Humira®, Remicade®) and within four to six weeks for others (Rituxan®, Orencia®). Biologics may be used alone or in combination with other DMARDs (eg, methotrexate), NSAIDs, and/or steroids.

Because of their cost (generally more than $15,000 per year in the United States), 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.

All biologic response modifiers must be injected. Humira®, Enbrel®, and Kineret® are injected under the skin by the patient, a family member, or nurse. Remicade®, Orencia® and Rituxan® 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 response modifiers interfere with the immune system's ability to fight infection and should not be used in people with serious infections.

Testing for tuberculosis 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".)

TNF-inhibitors 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. TNF-inhibitors have been associated with a further increase in the risk of lymphoma in some studies; more research is needed to define this risk.

Steroids (glucocorticoids) — Glucocorticoids, also called steroids have strong anti-inflammatory 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.

However, when used alone, glucocorticoids only modestly reduce damage to cartilage and bone caused by rheumatoid arthritis. 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 begin to work.

Side effects — Steroids have many 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.

Simple analgesics — Simple analgesics relieve pain, but they have no effect on inflammation. Drugs in this class include acetaminophen (Tylenol®), tramadol (Ultram®), and capsaicin cream or ointment (Zostrix®). Use of narcotic analgesics such as such as codeine, oxycodone, and hydrocodone is generally discouraged 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. Alternately, 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 DO I NEED?

The type and sequence of drugs used for rheumatoid arthritis treatment depends upon three factors: the activity, severity, and stage of rheumatoid arthritis.

Activity of rheumatoid arthritis — The activity of rheumatoid arthritis refers to the presence of joint swelling (inflammation).

Severity of rheumatoid arthritis — The severity of rheumatoid arthritis is based upon the severity of inflammation. Severity is classified as mild, moderate, or severe.

Mild — A person with mild rheumatoid arthritis has some of the following signs and symptoms:

• Joint pain
• Inflammation of at least three joints
• No inflammation in tissues other than the joints
• Usually, a negative result on a rheumatoid factor test
• An elevated ESR or CRP level
• No evidence of bone or cartilage damage on x-rays

Mild rheumatoid arthritis is usually treated initially with nonpharmacologic therapies and an NSAID. Only one NSAID is recommended at a time. This combination is continued only until inflammation has subsided. (See "Treatment of early, mildly active rheumatoid arthritis in adults".)

If one or more joints remain swollen or tender after a few weeks of treatment with an NSAID, one or more DMARDs may be recommended, including methotrexate, hydroxychloroquine, or sulfasalazine. These medications are discussed in more detail in a separate topic review. (See "Patient information: Disease modifying antirheumatic drugs (DMARDs)".)

Oral glucocorticoids (steroids) are not frequently recommended for people with mild rheumatoid arthritis. However, a glucocorticoid may be injected into a joint that is particularly painful; this can quickly reduce pain and swelling until the DMARDs begin to work.

More aggressive therapy is needed if rheumatoid arthritis remains active or progresses after three to six months of treatment with hydroxychloroquine and/or sulfasalazine. (See 'Moderate' below,").

Moderate — A person with moderate rheumatoid arthritis has a combination of the following signs and symptoms:

• Between 6 and 20 inflamed joints
• Usually no inflammation in tissues other than the joints
• An elevated ESR or CRP levels
• A positive rheumatoid factor test or anti-cyclic citrullinated peptide (anti-CCP) antibodies
• Evidence of inflammation but no evidence of bone damage on x-rays

Moderate rheumatoid arthritis is initially treated with nonpharmacologic therapies, a high dose NSAID, and one or more DMARD.

A clinician may also recommend short-term treatment with an oral glucocorticoid; this can relieve symptoms until the DMARD becomes effective. The glucocorticoid may be injected directly into one or a few joints to rapidly control inflammation and pain.

A biologic response modifier may be recommended if inflammation persists despite high doses of one or more DMARDs or if you cannot take methotrexate. In this case, an anti-TNF agent, such as etanercept, adalimumab, or infliximab, is usually recommended, along with methotrexate (see 'Biologic response modifiers' above. If one anti-TNF agent is ineffective or causes bothersome side effects, a second anti-TNF treatment may be tried. Alternately, another biologic agent, such as abatacept or rituximab, may be tried.

Severe — A person with severe rheumatoid arthritis has one or more of the following signs and symptoms:

• More than 20 persistently inflamed joints or a rapid loss of functional abilities
• Elevated ESR or CRP levels
• Anemia related to chronic illness
• Low blood albumin level
• A positive rheumatoid factor test, often with a high level
• Evidence of bone and cartilage damage on x-ray
• Inflammation in tissues other than joints

Severe rheumatoid arthritis is initially treated with nonpharmacologic therapies and NSAIDs plus one or more of the DMARDs. (See "Treatment of early, severely active rheumatoid arthritis in adults".)

Methotrexate is the DMARD of choice; it is usually taken by mouth initially, and the dose may be increased as frequently as every week or two. As the dose is increased, the healthcare provider may recommend that methotrexate be injected under the skin (subcutaneous) or into a muscle (intramuscular) to minimize bothersome side effects such as upset stomach and sore mouth. A second and perhaps third DMARD may be recommended in addition to methotrexate.

Oral glucocorticoids may be recommended if there are symptoms of widespread inflammation, such as fever (see 'Steroids (glucocorticoids)' above.

A biologic response modifier may be recommended if you have severe disease and do not respond adequately to methotrexate. If one anti-TNF treatment is ineffective or causes bothersome side effects, a second anti-TNF agent may be tried. Alternately, another biologic agent, such as abatacept or rituximab, may be tried.

Stage of rheumatoid arthritis — The stage of rheumatoid arthritis helps to determine which treatments are best. There are three stages: early, persistently active, and end-stage rheumatoid arthritis.

Early — A person with early rheumatoid arthritis has had evidence of inflammation for no more than six months. The goal of early rheumatoid treatment is to aggressively slow or stop ongoing inflammation and protect the joints.

Persistently active — A person with persistently active rheumatoid arthritis has had evidence of inflammation for at least six to twelve months and may have irreversible joint damage and loss of function. (See "Treatment of persistently active rheumatoid arthritis in adults".)

End-stage — 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".)

CLINICAL TRIALS

Researchers are continually conducting clinical trials of rheumatoid arthritis treatments to find better ways of treating the disease. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. For more information about clinical trials, visit http://clinicaltrials.gov/

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

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)

Professional Level Information:
Assessment of rheumatoid arthritis activity in clinical trials and clinical practice
Cervical subluxation in rheumatoid arthritis
Clinical features of rheumatoid arthritis
Clinical manifestations and diagnosis of polyarticular onset juvenile rheumatoid arthritis
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
Management of polyarticular onset juvenile rheumatoid arthritis
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

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus/arthritis.html, available in Spanish)

• National Institute of Arthritis and Musculoskeletal and Skin Diseases

      (301) 496-8188
      (www.niams.nih.gov/Health_Info/Arthritis/default.asp)

• National Institute on Aging

      (www.nia.nih.gov/HealthInformation/Publications/arthritis.htm, available in Spanish)

• American College of Rheumatology

      (404) 633-3777
      (www.rheumatology.org/public/factsheets/diseases_and_conditions/index.asp)

• The Arthritis Foundation

      (800) 283-7800
      (www.arthritis.org)

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

      (http://arthritis.about.com/forum)

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