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At the heart of general practice since 1960

Tight control in rheumatoid arthritis improves outcomes

How should rheumatoid arthritis be diagnosed?
When is aggressive treatment justified?
Which patients need urgent specialist assessment?

How should rheumatoid arthritis be diagnosed?
When is aggressive treatment justified?
Which patients need urgent specialist assessment?

The management of rheumatoid arthritis (RA) has undergone major changes over the past decade. GPs have a pivotal role to play particularly with regard to early identification of disease and rapid referral. In an average GP practice of 10,000 patients at least 5 new cases of RA will be seen per year not including other types of inflammatory arthritis. As the prevalence is 1% GPs may have around 100 patients with RA on their list. The age range most commonly affected by RA is 30 to 70 years.1,2

The old paradigm of ‘start low, go slow' has been rejected and a new therapeutic approach has been developed with early, intensive intervention in all patients with RA or suspected RA. Furthermore, in patients with definite RA, regular review with tight control using predefined disease activity measures has been found to improve outcomes.

The recently published guideline from NICE on the evidence-based management of RA in adults is greatly welcomed.3

RA is a chronic systemic autoimmune condition of unknown aetiology. It is characterised by synovial joint inflammation and destruction and extra-articular manifestations are common.

Unfettered disease leads to persistent symptoms, progressive loss of physical function, and premature mortality most frequently from cardiovascular disease.

RA impacts not only on the individual but also their families and carers. It also places a burden on the NHS leading to substantial social and economic costs.

Diagnosis

The diagnosis of RA has traditionally been based on a combination of clinical and laboratory findings supported by radiological changes. The American Rheumatism Association (ARA) 1987 criteria for RA, initially used to classify established disease for standardisation in clinical trials, became surrogate diagnostic criteria (see table 1, attached).

With the evolving concept of early inflammatory arthritis or very early RA, the ARA criteria have become inadequate in the clinic and nodules are usually late features and rheumatoid factor (RF) and erosions may be absent at the time of diagnosis. NICE has taken the bold, yet progressive, step of accepting a clinical diagnosis of RA as being more important than the ARA criteria.

Defining early inflammatory arthritis/RA still remains difficult. Many rheumatologists now consider six weeks of symptoms, such as pain, morning stiffness lasting more than 30 minutes and swelling of joints, sufficient to warrant treatment.4 The NICE guideline recommends that any patient with suspected persistent synovitis of undetermined cause should be referred to a specialist. Furthermore urgent referral should occur in any person with:
• involvement of the small joints of the hands or feet
• more than one joint affected
• a delay of three months or longer between onset of symptoms and seeking medical advice.

Patients with new or possible RA should be investigated for the presence of raised inflammatory markers (ESR and CRP) and rheumatoid factor (RF) by their GP. Further investigations can be undertaken once referral has been made to the specialist. Testing for RF may be misleading as it is non-specific, especially in low titres in elderly people. However, when the index of suspicion remains high for RA and the RF is negative, testing for anti-CCP antibodies (which are more specific for RA and present in up to 40% of RA patients who are RF-negative in early disease) should be undertaken. In addition, these antibodies have predictive value as anti-CCP positive patients have greater functional decline and more rapid radiological progression.5 Research is ongoing to determine whether testing for these antibodies is appropriate in primary care.

It is worth noting that urgent referral should be considered in any patient with suspected persistent synovitis whose blood tests do not show an acute phase response or negative RF.

Although crude in the light of modern imaging techniques, such as ultrasound and MRI, which are more sensitive for detecting synovitis than clinical examination, plain radiography of the hands and feet should be undertaken at baseline to look for early erosive disease. It is also still recommended for monitoring response to therapy.

Advances in management

The current target for treating RA is to suppress inflammation as completely as possible. This in turn should retard and potentially abrogate radiographic progression, improve function, reduce disability and the comorbidities associated with RA and lower the risk of early death.

Early aggressive therapy

Therapeutic intervention should occur as soon as possible after symptom development. There is a therapeutic ‘window of opportunity' in early disease, where the condition may be more responsive to intervention, hence appropriate treatment may lead to induction of remission with the potential of stopping medication entirely.6,7 Early inflammatory arthritis may therefore be considered, in some respects, a medical emergency. This management approach underscores the need for rapid access to specialist care with NICE endorsing frequent review when and where the patient desires (see below).

Use of single DMARD therapy has been common, but the importance of early combination DMARD therapy has also been highlighted by NICE, see figure 2, attached. Methotrexate should be used as the anchor drug in combination with another DMARD such as hydroxychloroquine or sulphasalazine unless contraindicated. Judicious use of corticosteroids may also be beneficial especially in the early stage of disease or during disease flares.

Biological agents

The arsenal against RA has improved with the arrival of biological agents which target specific components of the immune system. TNF alpha inhibitors including infliximab, adalimumab and etanercept have proven their worth in multiple randomised trials and in clinical practice, and have been approved by NICE.8 The B-cell depleting agent rituximab has been approved for patients who have not responded to anti-TNF alpha agents.9

Monitoring

Current evidence suggests that tight control of RA, similar to that undertaken in the management of diabetes, improves outcomes.10 Paradigms which include constant reassessment and individual tailoring of therapy to achieve remission, using predefined thresholds of disease activity, are vitally important. Clinicians should no longer rely on gestalt estimates of disease activity - rather objective measures of disease need to be incorporated into daily practice. One such tool is the disease activity score (DAS) comprising a composite of swollen joint count, tender joint count, VAS and ESR or CRP.

The DAS is well established in rheumatological practice and is used to determine disease activity at a single time point. This allows individualised therapeutic changes to be made depending upon the result.

Symptom control

It should never be forgotten that the chief concern of the patient with RA is symptom control. Medications such as paracetamol, codeine and compound analgesics need to be prescribed in order to achieve this. In addition it is clear that NSAIDs/COX-2 inhibitors are effective anti-inflammatory medications and should be used in RA patients.

Two major limitations of these therapies are their toxicity and lack of disease-modifying effect. Hence NICE has emphasised that the smallest effective dose of NSAID/COX-2 inhibitors should be used for the shortest period of time in patients with RA. Therapy should be withdrawn intermittently to assess whether there is an ongoing requirement for the drugs. A PPI should be coprescribed to avoid GI bleeding complications.

Withdrawal of treatment

Once a patient has been well controlled for a period it may be possible to wean them off therapy. Corticosteroids should be withdrawn initially followed by NSAIDs/COX-2 inhibitors. If the condition continues to remain in remission then cautious withdrawal of DMARD therapy may be trialled. If symptoms recrudesce then therapy should be reintroduced forthwith.

Regular review

It is critical that RA management is patient-centred and the varied aspects of disease need to be addressed in individual patients. NICE has recommended that all patients with RA should be offered an annual review in order to assess:
• Disease activity and damage
• Functional ability
• Comorbidities e.g. hypertension, IHD, osteoporosis, depression
• Complications e.g. vasculitis, cervical spine, lung or eye disease
• Need for cross referral within the multidisciplinary team (see below)
• Need for surgery
• Impact of RA on lifestyle

In those patients with recent-onset active RA monthly review is required until the condition has been controlled to the satisfaction of both the patient and clinician. In controlled, established RA review appointments should be tailored to the patient's needs including frequent appointments if required at a suitable location. The frequency of review suggested by NICE has significant service provision implications. Liaison with local commissioners and/or providers is imperative in order to implement best practice.

The multidisciplinary team

The management of RA is a lesson in the value of the multidisciplinary team. It is critical that patients have access to physiotherapy, occupational therapy, podiatry, social and psychological support as well as surgical intervention where required. Rheumatology nurses are indispensable in overseeing the patient's management. NICE suggests that patients should have a named member of the team who is responsible for co-ordinating their care. A clear plan should be formulated with the patient regarding their treatment with information supplied verbally and in written form. Patients, and if appropriate their carers and families, should be allowed to discuss, and agree, all aspects of their care and their decisions should be respected.

GPs play a critical role in identifying disease for early, urgent referral and in monitoring the patient and DMARD therapy. Many practices have shared care guidelines whereby medications are reviewed regularly and appropriate blood tests are undertaken to check for drug toxicity. This optimises the care of the patient and acts as a fail-safe in detecting potential side-effects.

Smooth and expedious transition from primary to secondary care with continued close collaboration in monitoring disease can only benefit RA patients to achieve the goal of remission. The recent NICE guideline is essential to facilitate this process.

Useful information

National Rheumatoid Arthritis Society
www.rheumatoid.org.uk

Arthritis Care
www.arthritiscare.org.uk

Arthritis Research Campaign
www.arc.org.uk

British Society for Rheumatology
www.rheumatology.org.uk

European League Against Rheumatism (EULAR)
www.eular.org

Arthritis and Musculoskeletal Alliance
www.arma.uk.net

Authors

Dr Andrew J K Östör
MB BS FRACP
consultant rheumatologist and
associate lecturer
School of Clinical Medicine
University of Cambridge
Director, Rheumatology Clinical Research Unit

Professor Philip G Conaghan
MB BS PhD FRACP FRCP
Professor of Musculoskeletal Medicine
University of Leeds
consultant rheumatologist
Leeds Teaching Hospitals NHS Trust

Key points Table 1: Summary of 1987 ARA classification criteria for rheumatoid arthritis Figure 2: Pharmacological management of rheumatoid arthritis: DMARDs and biological agents

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