Management of Rheumatoid Arthritis

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PatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

See also: Rheumatoid Arthritis written for patients

Rheumatoid arthritis (RA) is a chronic systemic disease. Early diagnosis of RA and effective treatment with disease-modifying antirheumatic drugs (DMARDs) are essential to reduce joint destruction and disability.[1] An increasing range of DMARDs is now available.[2] 

Late diagnosis of RA greatly increases the risk of erosive joint damage. Once mechanical damage has occurred, pain and joint deformity often require aids and appliances and, eventually, surgery.[1] Current guidance is that patients with suspected RA should be referred to a rheumatologist as soon as possible so that disease-modifying agents can be started early in the condition.[3] The window of opportunity in which disease-modifying drugs can prevent joint damage is only a few months.[4] 

  • The National Institute for Health and Care Excellence (NICE) recommends referral of any person with suspected persistent synovitis of undetermined cause for specialist opinion. Refer urgently if any of the following apply:[5]
    • The small joints of the hands or feet are affected.
    • More than one joint is affected.
    • There has been a delay of three 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 C-reactive protein (CRP) and ESR or a negative rheumatoid factor.
  • Doctors and patients can use Decision Aids together to help choose the best course of action to take.
  • Compare the options  
  • Whilst waiting for specialist assessment, non-drug measures and symptomatic treatment - such as simple analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) - can be instituted. At any stage the use of simple analgesia should be considered as an adjunct. Drugs to suppress neuropathic pain, such as carbamazepine or amitriptyline, may also be beneficial.
  • Management should include a multidisciplinary team (MDT). All patients should have access to a range of professionals, including GP, rheumatologist, nurse specialist, physiotherapist, occupational therapist, dietician, podiatrist, pharmacist, and social worker.[6]

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Referral for specialist treatment[5]

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 three months or longer between onset of symptoms and seeking medical advice.

Monitoring disease[5]

  • 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.
  • The DAS28 is a measure of disease activity in RA. The score is calculated by a complex mathematical formula, which includes the number of tender and swollen joints (out of a total of 28 - shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints and the knees), the ESR, and the patient's 'assessment of global health'. A DAS28 score greater than 5.1 implies active disease, less than 3.2 well-controlled disease, and less than 2.6 remission.[7]
  • Screen for comorbid conditions - eg, osteoporosis, depression, infection and cardiovascular disease (CVD).[8]

Non-drug management

The importance of the MDT is emphasised in the NICE guidance:[5]

  • RA patients should have access to a named member of the MDT who is responsible for co-ordinating their care (often a specialist nurse).
  • RA patients should have easy access to physiotherapy, occupational therapy, psychological services and podiatry. There should be regular review, particularly with physiotherapy and occupational therapy.
  • The core members of the MDT will be the GP, the rheumatologist, physiotherapists and occupational therapists. Other specialties that may need to be involved include podiatrists, orthotists, dieticians, pharmacists and neurologists.
  • Exercise has been found to reduce bone loss in premenopausal women with RA.[9]
  • Pain clinic specialists may be able to advise on non-drug management options, such as transcutaneous electrical nerve stimulation (TENS) and behavioural approaches.[1] 
  • Non-clinical issues may need the assistance of social workers, voluntary organisations and wheelchair services.

Analgesics[5]

Analgesics (eg, paracetamol, codeine or compound analgesics) should be offered to people with RA whose pain control is not adequate, to potentially reduce their need for long-term treatment with NSAIDs or cyclo-oxygenase-2 (COX-2) inhibitors.

NSAIDs

For example: ibuprofen, diclofenac, naproxen.

  • NICE recommends prescribing with a suitable proton pump inhibitor (PPI).[5]
  • NSAIDs improve symptoms and signs of RA. They are highly effective and many RA patients rely on them, but they do not slow progression or long-term disability.
  • NSAIDs have a rapid onset of action. The most commonly used NSAIDs are ibuprofen, diclofenac and naproxen.
  • NSAIDs can interact with diuretics (reduced effect in renal toxicity), warfarin (risk of bleeding), lithium (toxicity) and methotrexate (marrow toxicity). See individual drug monographs.

COX-2 drugs

For example: celecoxib, etoricoxib.

  • NICE recommends prescribing with a suitable PPI.[5]
  • COX-2 selective drugs have very similar efficacy to standard NSAIDs, although patients report individual differences. COX-2 selective NSAIDs are more expensive.
  • COX-2s are contra-indicated in coronary heart disease, cerebrovascular disease, peripheral arterial disease, and mild-to-severe heart failure.[10] 

Corticosteroids[6]

  • Low-dose oral corticosteroids can be used in combination with DMARD therapy for short-term relief of signs and symptoms, and in the medium to long term to minimise radiological damage.
  • Short-term treatment with glucocorticoids (oral, intramuscular or intra-articular) to rapidly improve symptoms should be considered in people with newly diagnosed RA if they are not already receiving glucocorticoids as part of DMARD combination therapy.[5]
  • Intra-articular corticosteroid injections can be used to:
    • Provide symptomatic relief pending the onset of DMARD effect.
    • Alleviate symptoms in particularly troublesome joints where the overall disease control is good.
    • Deal with monoarthritis/oligoarthritis in instances when DMARDs are deemed inappropriate.

DMARDs

See also separate Disease-modifying Antirheumatic Drugs (DMARDs) article.

  • DMARDs include azathioprine, ciclosporin, d-penicillamine, hydroxychloroquine, leflunomide, methotrexate, mycophenolate mofetil (MMF), sodium aurothiomalate, sulfasalazine.[2]
  • Early initiation of treatment with DMARDs is recommended to control the symptoms and signs of RA as well as limiting radiological damage.[6]
  • Methotrexate and sulfasalazine are the DMARDs of choice, due to their more favourable efficacy and toxicity profiles. DMARD therapy should be sustained in patients with early RA, to control the signs and symptoms of disease. A combination DMARD strategy, rather than sequential monotherapy, should be considered in patients with an inadequate response to initial DMARD therapy.[6]
  • They are instituted by specialists as soon as diagnosis, progression and severity of the disease have been confirmed. 'Tight control' is the aim, which means increasing the therapy whenever the disease is not fully suppressed.
  • 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 three months of the onset of persistent symptoms.[5]
  • In people with newly diagnosed RA for whom combination DMARD therapy is not appropriate, start DMARD monotherapy, placing greater emphasis on fast escalation to a clinically effective dose rather than on the choice of DMARD.[5]
  • 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.[5]

Biological therapies

Biological therapies (cytokine modulators) have been shown to be effective in the treatment of RA, including patients resistant to methotrexate. The following are approved for treatment of RA:[11]

  • Tumour necrosis factor (TNF) inhibitors: adalimumab, certolizumab pegol, etanercept, golimumab, infliximab.
  • Anti-interleukin-1 therapy: anakinra.
  • T-cell co-stimulator modulator: abatacept.
  • Anti-CD20 therapy: rituximab.
  • Anti-interleukin-6 receptor therapy: tocilizumab.

NICE recommends that in addition to low-dose glucocorticoids, two trials of six months of traditional DMARD monotherapy or combination therapy (at least one including methotrexate) should fail to control symptoms or prevent disease progression before a biological therapy be recommended. A trial of a DMARD is defined as being normally of six months, with two months at standard dose, unless significant toxicity has limited the dose or duration of treatment.[5]

  • The TNF-alpha inhibitors adalimumab, etanercept, infliximab and certolizumab pegol are recommended as options for the treatment of adults who have severe active RA and have undergone trials of two DMARDs, including methotrexate (unless contra-indicated).[12][13]
  • Treatment with adalimumab, etanercept, infliximab, abatacept and certolizumab pegol should be continued only if there is an adequate response six months after initiation of therapy. Treatment should be monitored at least every six months and continued only if an adequate response is maintained.[12][13]
  • Following failure of TNF inhibitor treatment:
      • Rituximab in combination with methotrexate is recommended as an option for the treatment of adults with severe active RA who have had an inadequate response to, or are intolerant of, other DMARDs, including at least one TNF inhibitor. Treatment with rituximab should be given no more frequently than every six months.[14]
      • Adalimumab, etanercept, infliximab and abatacept, each in combination with methotrexate, are recommended as treatment options for adults with severe active RA who have had an inadequate response to, or have an intolerance of, other DMARDs, including at least one TNF inhibitor, and who cannot receive rituximab.[14]
      • Adalimumab monotherapy and etanercept monotherapy are recommended as treatment options for adults with severe active RA who have had an inadequate response to, or have an intolerance of, other DMARDs, including at least one TNF inhibitor, and who cannot receive rituximab therapy because they are unable to be treated with methotrexate.[14]
    • Tocilizumab in combination with methotrexate is recommended as an option for the treatment of rheumatoid arthritis in adults if:[15] 
      • The disease has responded inadequately to DMARDs.
      • The disease has responded inadequately to DMARDs and a TNF inhibitor and the person cannot receive rituximab because of a contra-indication to rituximab, or because rituximab is withdrawn because of an adverse event.
      • The disease has responded inadequately to one or more TNF inhibitor treatments and to rituximab.
  • Abatacept in combination with methotrexate is recommended as an option for treating rheumatoid arthritis in adults whose disease has responded inadequately to two conventional DMARDs, including methotrexate.[16] 

Diet and complementary therapies

  • There is no strong evidence that patients with RA will benefit from changes in diet.
  • A Mediterranean diet should be encouraged (more bread, fruit, vegetables and fish; less meat; and replace butter and cheese with products based on vegetable and plant oils).[5]
  • Complementary therapies may provide short-term symptomatic benefit but there is little or no evidence of long-term benefit.

    Advise RA patients who wish to try complementary therapies:
    • That they should not replace conventional treatment.
    • That this should not affect the care offered by any member of the MDT.

Patients should be offered an annual review by a hospital specialist or GP with special interest to:[5]

  • 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, coronary heart disease, osteoporosis and depression.
  • Assess for complications, such as vasculitis and disease of the cervical spine, lung or eyes.
  • Organise appropriate referrals within the MDT whenever appropriate.
  • Assess the need for referral for surgery.
  • Also, review the effectiveness and adverse effects of medication.
  • Assess the effect the disease is having on the patient's personal life (for example, the capacity to work, study, mix socially and remain financially viable).

The opinion of an orthopaedic surgeon with a special interest in RA should be sought in patients who are on maximum tolerated therapy but have uncontrollable pain and/or significant restrictions of joint movement.

NICE guidance on referral for surgery

Refer people with RA for an early specialist surgical opinion if the following do not respond to optimal non-surgical management:

  • Persistent pain (from, for example, joint damage or other soft tissue cause).
  • Worsening joint function.
  • Progressive deformity.
  • Persistent localised synovitis.

Refer people with complications for a specialist surgical opinion before damage or deformity becomes irreversible:

  • Imminent or actual tendon rupture.
  • Nerve entrapment (for example, carpal tunnel syndrome).
  • Any stress fracture.

Refer urgently for:

  • Suspected or proven septic arthritis (especially in a prosthetic joint).
  • Any symptoms or signs that suggest cervical myelopathy.

Do not let concerns about the long-term durability of prosthetic joints influence decisions to offer joint replacements to younger people with RA.

Further reading & references

  1. Guideline for the management of rheumatoid arthritis (first 2 years); British Society for Rheumatology (July 2006)
  2. Guideline for disease-modifying anti-rheumatic drug (DMARD) therapy; British Society for Rheumatology and British Health Professionals in Rheumatology (2008)
  3. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update; European League Against Rheumatism (Dec 2013)
  4. Valesini G, Di Franco M, Spinelli FR, et al; Induction of remission in rheumatoid arthritis: criteria and opportunities. Rheumatol Int. 2008 Dec;29(2):131-9. Epub 2008 Sep 21.
  5. Rheumatoid arthritis: the management of rheumatoid arthritis in adults; NICE Clinical Guideline (February 2009)
  6. Management of early rheumatoid arthritis; Scottish Intercollegiate Guidelines Network - SIGN (February 2011)
  7. DAS28 Score; National Rheumatoid Arthritis Society
  8. BSR and BHPR guideline for the management of rheumatoid arthritis (after the first 2 years); British Society for Rheumatology and British Health Professionals in Rheumatology (January 2009)
  9. Tourinho TF, Capp E, Brenol JC, et al; Physical activity prevents bone loss in premenopausal women with rheumatoid arthritis: a cohort study. Rheumatol Int. 2008 Aug;28(10):1001-7. Epub 2008 Mar 4.
  10. British National Formulary; 68th Edition (Sep 2014) British Medical Association and Royal Pharmaceutical Society of Great Britain, London
  11. Tugwell P, Singh JA, Wells GA; Biologicals for rheumatoid arthritis. BMJ. 2011 Jul 28;343:d4027. doi: 10.1136/bmj.d4027.
  12. Rheumatoid arthritis - adalimumab, etanercept and infliximab; NICE Technology Appraisal Guidance, October 2007
  13. Certolizumab pegol for the treatment of rheumatoid arthritis; NICE Technology Appraisal Guidance, February 2010
  14. Adalimumab, etanercept, infliximab, rituximab and abatacept for the treatment of rheumatoid arthritis after the failure of a TNF inhibitor; NICE Technology Appraisal Guidance, August 2010
  15. Tocilizumab for the treatment of rheumatoid arthritis ; NICE Technology Appraisal Guidance, February 2012
  16. Abatacept for treating rheumatoid arthritis after the failure of conventional disease-modifying anti-rheumatic drugs ; NICE Technology Appraisal Guidance, April 2013

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Laurence Knott
Current Version:
Peer Reviewer:
Dr John Cox
Document ID:
318 (v27)
Last Checked:
27/01/2015
Next Review:
26/01/2020

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