Note from the National Guideline Clearinghouse: This guideline references a drug(s) for which important revised regulatory and/or warning information has been released.

Note from the National Guideline Clearinghouse (NGC): This guideline was developed by the National Collaborating Centre for Chronic Conditions (NCC-CC) on behalf of the National Institute for Health and Clinical Excellence (NICE). See the "Availability of Companion Documents" field for the full version of this guidance.

The Guideline Development Group (GDG) accepted a clinical diagnosis of Rheumatoid Arthritis (RA) as being more important than the 1987 American Rheumatism Association classification criteria. This is because an early persistent synovitis, in which other pathologies have been ruled out, needs to be treated as if it is RA to try to prevent damage to joints. International committees are addressing the diagnostic criteria for early RA.

The GDG categorised RA into two categories: 'recent onset' (disease duration of up to 2 years) and 'established' (disease duration of longer than 2 years). Within recent-onset RA, categories of suspected persistent synovitis or suspected RA refer to patients in whom a diagnosis is not yet clear, but in whom referral to specialist care or further investigation is required.

Referral, Diagnosis and Investigations

Referral for Specialist Treatment

• Refer for specialist opinion any person with suspected persistent synovitis of undetermined cause. Refer urgently if any of the following apply:
  • The small joints of the hands or feet are affected
  • More than one joint is affected
  • There has been a delay of 3 months or longer between onset of symptoms and seeking medical advice
• Do not avoid referring urgently any person with suspected persistent synovitis of undetermined cause whose blood tests show a normal acute-phase response or negative rheumatoid factor.

Investigations

• Offer to carry out a blood test for rheumatoid factor in people with suspected RA who are found to have synovitis on clinical examination.
• Consider measuring anti-cyclic citrullinated peptide (CCP) antibodies in people with suspected RA if:
  • They are negative for rheumatoid factor
  • There is a need to inform decision-making about starting combination therapy (see section "Introducing and Withdrawing DMARDS" under "Pharmacological Management" below).
• X-ray the hands and feet early in the course of the disease in people with persistent synovitis in these joints.

Communication and Education

• Explain the risks and benefits of treatment options to people with RA in ways that can be easily understood. Throughout the course of their disease, offer them the opportunity to talk about and agree all aspects of their care, and respect the decisions they make.
• Offer verbal and written information to people with RA to:
  • Improve their understanding of the condition and its management
  • Counter any misconceptions they may have
• People with RA who wish to know more about their disease and its management should be offered the opportunity to take part in existing educational activities, including self-management programmes.

The Multidisciplinary Team

• People with RA should have ongoing access to a multidisciplinary team. This should provide the opportunity for periodic assessments (see under "Monitoring Rheumatoid Arthritis" below) of the effect of the disease on their lives (such as pain, fatigue, everyday activities, mobility, ability to work or take part in social or leisure activities, quality of life, mood, impact on sexual relationships) and help to manage the condition.
• People with RA should have access to a named member of the multidisciplinary team (for example, the specialist nurse) who is responsible for coordinating their care.
• People with RA should have access to specialist physiotherapy, with periodic review (see under "Monitoring Rheumatoid Arthritis" below), to:
  • Improve general fitness and encourage regular exercise
  • Learn exercises for enhancing joint flexibility, muscle strength and managing other functional impairments
  • Learn about the short-term pain relief provided by methods such as transcutaneous electrical nerve stimulators [TENS] and wax baths
• People with RA should have access to specialist occupational therapy, with periodic review (see under "Monitoring Rheumatoid Arthritis" below), if they have:
  • Difficulties with any of their everyday activities
  • Problems with hand function
• Offer psychological interventions (for example, relaxation, stress management and cognitive coping skills [such as managing negative thinking]) to help people with RA adjust to living with their condition.
• All people with RA and foot problems should have access to a podiatrist for assessment and periodic review of their foot health needs (see under "Monitoring Rheumatoid Arthritis" below).
• Functional insoles and therapeutic footwear should be available for all people with RA if indicated.

Pharmacological Management

Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

Introducing and Withdrawing DMARDs

• In people with newly diagnosed active RA, offer a combination of DMARDs (including methotrexate and at least one other DMARD, plus short-term glucocorticoids) as first-line treatment as soon as possible, ideally within 3 months of the onset of persistent symptoms.
• Consider offering short-term treatment with glucocorticoids (oral, intramuscular or intra-articular) to rapidly improve symptoms in people with newly diagnosed RA if they are not already receiving glucocorticoids as part of DMARD combination therapy.
• In people with recent-onset RA receiving combination DMARD therapy and in whom sustained and satisfactory levels of disease control have been achieved, cautiously try to reduce drug doses to levels that still maintain disease control.
• In people with newly diagnosed RA for whom combination DMARD therapy is not appropriate (for example, because of comorbidities or pregnancy, during which certain drugs would be contraindicated), start DMARD monotherapy, placing greater emphasis on fast escalation to a clinically effective dose rather than on the choice of DMARD.
• In people with established RA whose disease is stable, cautiously reduce dosages of disease-modifying or biological drugs. Return promptly to disease-controlling dosages at the first sign of a flare.
• When introducing new drugs to improve disease control into the treatment regimen of a person with established RA, consider decreasing or stopping their pre-existing rheumatological drugs once the disease is controlled.
• In any person with established rheumatoid arthritis in whom disease-modifying or biological drug doses are being decreased or stopped, arrangements should be in place for prompt review.

Glucocorticoids

• Offer short-term treatment with glucocorticoids for managing flares in people with recent-onset or established disease to rapidly decrease inflammation.
• In people with established RA, only continue long-term treatment with glucocorticoids when:
  • The long-term complications of glucocorticoid therapy have been fully discussed
  • All other treatment options (including biological drugs) have been offered

Biological Drugs

• Please see the section below for other NICE technology appraisal guidance on biological drugs for RA.
• On the balance of its clinical benefits and cost effectiveness, anakinra is not recommended for the treatment of RA, except in the context of a controlled, long-term clinical study*.
• Patients currently receiving anakinra for RA may suffer loss of well-being if their treatment were discontinued at a time they did not anticipate. Therefore, patients should continue therapy with anakinra until they and their consultant consider it is appropriate to stop*.

  *Note: These recommendations are from 'Anakinra for rheumatoid arthritis', NICE technology appraisal guidance 72. The GDG reviewed the evidence on anakinra but made no changes to the recommendations.

• Do not offer the combination of tumour necrosis factor-alpha (TNF-alpha) inhibitor therapy and anakinra for RA.

Symptom Control

The recommendations under the second through fourth bullets in this section replace the rheumatoid arthritis aspects only of 'Guidance on the use of cyclo-oxygenase (COX) II selective inhibitors, celecoxib, rofecoxib, meloxicam and etodolac for osteoarthritis and rheumatoid arthritis' (See the NICE technology appraisal guidance 27).

• Offer analgesics (for example, paracetamol, codeine or compound analgesics) to people with RA whose pain control is not adequate, to potentially reduce their need for long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or cyclo-oxygenase-2 (COX-2) inhibitors.
• Oral NSAIDs/COX-2 inhibitors should be used at the lowest effective dose for the shortest possible period of time.
• When offering treatment with an oral NSAID/COX-2 inhibitor, the first choice should be either a standard NSAID or a COX-2 inhibitor (other than etoricoxib 60 mg). In either case, these should be co-prescribed with a proton pump inhibitor (PPI), choosing the one with the lowest acquisition cost.
• All oral NSAIDs/COX-2 inhibitors have analgesic effects of a similar magnitude but vary in their potential gastrointestinal, liver and cardio-renal toxicity; therefore, when choosing the agent and dose, healthcare professionals should take into account individual patient risk factors, including age. When prescribing these drugs, consideration should be given to appropriate assessment and/or ongoing monitoring of these risk factors.
• If a person with RA needs to take low-dose aspirin, healthcare professionals should consider other analgesics before substituting or adding an NSAID or COX-2 inhibitor (with a PPI) if pain relief is ineffective or insufficient.
• If NSAIDs or COX-2 inhibitors are not providing satisfactory symptom control, review the disease-modifying or biological drug regimen.

Monitoring Rheumatoid Arthritis

• Measure CRP and key components of disease activity (using a composite score such as DAS28) regularly in people with RA to inform decision-making about:
  • Increasing treatment to control disease
  • Cautiously decreasing treatment when disease is controlled
• In people with recent-onset active RA, measure CRP and key components of disease activity (using a composite score such as DAS28) monthly until treatment has controlled the disease to a level previously agreed with the person with RA.
• Offer people with satisfactorily controlled established RA review appointments at a frequency and location suitable to their needs. In addition, make sure they:
  • Have access to additional visits for disease flares
  • Know when and how to get rapid access to specialist care
  • Have ongoing drug monitoring
• Offer people with RA an annual review to:
  • Assess disease activity and damage, and measure functional ability (using, for example, the Health Assessment Questionnaire [HAQ])
  • Check for the development of comorbidities, such as hypertension, ischaemic heart disease, osteoporosis and depression
  • Assess symptoms that suggest complications, such as vasculitis and disease of the cervical spine, lung or eyes
  • Organise appropriate cross referral within the multidisciplinary team
  • Assess the need for referral for surgery (see "Timing and Referral" below)
  • Assess the effect the disease is having on a person's life

Timing and Referral for Surgery

• Offer to refer people with RA for an early specialist surgical opinion if any of the following do not respond to optimal non-surgical management:
  • Persistent pain due to joint damage or other identifiable soft tissue cause
  • Worsening joint function
  • Progressive deformity
  • Persistent localised synovitis
• Offer to refer people with any of the following complications for a specialist surgical opinion before damage or deformity becomes irreversible:
  • Imminent or actual tendon rupture
  • Nerve compression (for example, carpal tunnel syndrome)
  • Stress fracture
• When surgery is offered to people with RA, explain that the main expected benefits are:
  • Pain relief
  • Improvement, or prevention of further deterioration, of joint function
  • Prevention of deformity

Note: Cosmetic improvements should not be the dominant concern.

• Offer urgent combined medical and surgical management to people with RA who have suspected or proven septic arthritis (especially in a prosthetic joint).
• If a person with RA develops any symptoms or signs that suggest cervical myelopathy (for example, paraesthesiae, weakness, unsteadiness, reduced power, extensor plantars)
  • Request an urgent magnetic resonance imaging scan
  • Refer for a specialist surgical opinion
• Do not let concerns about the long-term durability of prosthetic joints influence decisions to offer joint replacements to younger people with RA.

Diet and Complementary Therapies

• Inform people with RA who wish to experiment with their diet that there is no strong evidence that their arthritis will benefit. However, they could be encouraged to follow the principles of a Mediterranean diet (more bread, fruit, vegetables and fish; less meat; and replace butter and cheese with products based on vegetable and plant oils).
• Inform people with RA who wish to try complementary therapies that although some may provide short-term symptomatic benefit, there is little or no evidence for their long-term efficacy.
• If a person with RA decides to try complementary therapies, advise them:
  • These approaches should not replace conventional treatment
  • This should not prejudice the attitudes of members of the multidisciplinary team, or affect the care offered

Related NICE Technology Appraisal Guidance

The recommendations in this section are existing NICE technology appraisal guidance. They were formulated as part of the technology appraisals and not by the guideline developers. They have been incorporated into this guideline in line with NICE procedures for developing clinical guidelines, and the evidence to support the recommendations can be found with the individual appraisals.

Rituximab for the Treatment of Rheumatoid Arthritis (NICE Technology Appraisal Guidance 126)

This guideline offers best practice advice on the care of adults with RA.

The following are available:

The following is available:

This NGC summary was completed by ECRI on March 8, 2006. This NGC summary was updated by ECRI Institute on August 26, 2009.

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