Dr Louise Warburton explains how awareness of the symptoms of rheumatoid arthritis needs to be raised in both healthcare professionals and the public

It has been more than 12 months since the National Institute for Health and Care Excellence (NICE) released Clinical Guideline 79 on Management of rheumatoid arthritis in adults.1,2 This guidance has generally been well received within the rheumatology profession, as demonstrated in a recent edition of the UK journal, Rheumatology:

‘The NICE review is an exceptional piece of work, assembling vast amounts of information … producing a global evidence base for the assessment and treatment of RA. There is no equivalent single synthesis available elsewhere. Provided that this guidance is treated as guidance rather than as a standard, then it should result in better treatment of RA.’3

Early referral of patients with rheumatoid arthritis

One of the key recommendations for GPs in the NICE guideline on rheumatoid arthritis (RA) is:1,2

  • to refer any person with suspected synovitis of undetermined cause for specialist opinion. Referral should take place urgently if any of the following apply:
    • the small joints of the hands and feet are affected
    • more than one joint is affected
    • there has been a delay of more than 3 months between the onset of symptoms and seeking medical advice.

The guideline also recommends that GPs should not avoid urgent referral of a person with suspected persistent synovitis whose blood tests show a normal acute-phase response or negative rheumatoid factor.1,2

The NICE guideline on RA has been criticised because it does not define what synovitis is, or explain how GPs can detect it. During preparation of the guideline, the Guideline Development Group (GDG) was told very firmly that the guidance was not a textbook of rheumatology and should confine itself to recommendations, and not education. Hence, an element of education was not included.

I would agree that GPs find it difficult to detect synovitis and it is sometimes difficult to confirm that this is present, even in specialist care. However, the GDG wanted the guideline to have a strong emphasis on the importance of referral for anyone who has suspected synovitis for specialist assessment so that imaging modalities, such as ultrasound could be used to detect sub-clinical synovitis.1,2

Traditionally, GPs have also avoided referring patients whose blood tests are normal and the NICE guideline breaks new ground by suggesting that patients should be referred irrespective of blood test results. In my own personal specialist clinic, I have definitely noticed a change in GP referral patterns, with patients coming to the clinic sooner for assessment even with normal blood tests. But this may just be due to a local effect from spreading the message personally among my GP colleagues.

A report by the National Audit Office (NAO) in July 2009 analysed the provision of services for RA in the UK, by surveying patients, GPs, and specialist care. Overall findings showed that people with RA visit a GP, on average, four times before being referred to a specialist for diagnosis, and 18% visit more than eight times.4 Clearly this is not acceptable. A quarter of the 481 GP respondents told the survey that they did not have access to the support and advice they needed to help them to identify new cases of RA.4 Most GPs will only see one new patient with the disease each year and this does not allow them to build up a sufficient level of skill to enable them to make a diagnosis.

The NICE guideline has brought the subject of early diagnosis of inflammatory arthritis to the attention of GPs, but this work needs to be continued. The National Rheumatoid Arthritis Society (NRAS) has enlisted the help of GPs, GPs with a Special Interest (GPwSIs), allied health professionals, and Arthritis Research UK to devise a national campaign to raise the awareness of early RA and also ankylosing spondylitis to both GPs and patients (www.arthritisresearchuk.org). The campaign is called the ‘S factor’ and an example poster is shown in Figure 1. This will be distributed around all GP surgeries.

The S factor campaign should also increase the awareness of the general public about inflammatory arthritis, as well as GPs and practice nurses.

Public perception of RA
The NAO report also identified the fact that people who may have RA often delay in seeking medical help from their GP:4

  • Between one half and three quarters of people delay for 3 months or more following the onset of their symptoms
  • A fifth of people delay for a year or more.

It is well known that prompt treatment of RA with disease-modifying anti-rheumatic drugs (DMARDs) will limit disease progression and more work needs to be done to try and identify what prevents people from presenting to their GP. The general feeling is that this trend is due to a lack of awareness in the general population of the signs and symptoms of RA, and the impression that any joint pain is simply because of ageing and is therefore untreatable.

Figure 1: Raising awareness of rheumatoid arthritis: the S factor campaign

S Factor poster

This poster is part of a public awareness campaign developed by the Rheumatology Futures Project Group (RFPG—Ailsa Bosworth, Chief Executive of NRAS, Joint Chair of the RFPG) and endorsed and supported by Arthritis Research UK, the Royal College of General Practitioners, and the Primary Care Rheumatology Society. Available from: www.nras.org.uk/about_rheumatoid_arthritis/what_is_ra/how_is_it_diagnosed/have_you_got_s_factor.aspx


Treatment of RA

Previously, DMARDs were only introduced when a patient fulfilled the American College of Rheumatology (ACR) criteria for RA.5 It is now recognised that these criteria identify patients with well-established disease and there has been a move in recent years to commence therapy much earlier in the disease course. The use of combination therapies has been shown to be more effective at treating RA and this led to the development of the following NICE evidence statements:2

  • For symptoms, joint damage, function, and quality of life, delay in introducing DMARDs is inferior to early commencement6
  • Prompt introduction of DMARDs can lead to benefits for up to 5 years after the drugs are introduced when compared with a delayed start7
  • Early introduction of drugs also results in fewer adverse reactions and withdrawals7
  • There was some evidence that combination therapies could extend the window of opportunity for DMARDs to be effective when compared with monotherapies8
  • The key message to emerge was to start effective DMARD therapy as soon as possible.

These statements culminated in the following NICE recommendation: ‘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.1,2

This is definitely a change to established practice and from personal experience (through my own clinic and discussions with other GPwSIs and rheumatologists) this new advice is creating some controversy. There is a worry that combination therapies will cause more side-effects, but this has not been confirmed by studies. Additionally, if a patient is taking a combination of two or more drugs and a side-effect develops, it is difficult to know which treatment is responsible.

From a prescribing point of view, it is difficult for the patient to accept that they need to take multiple medications each day and also have blood tests as recommended by the British Society for Rheumatology monitoring guidelines.9 The prescriber may, therefore, be more reluctant to prescribe a combination of drugs.

Monitoring
NICE has also recommended monthly monitoring until the disease is under control.1,2 This is good news for patients and GPs, as there is a much greater chance that the disease will come under quick and tight control. However, this recommendation is causing problems within specialist rheumatology departments as it requires more patient appointments and more staff and in these times of economic hardship, this is difficult to achieve.

In my own area, the primary care trust (PCT) has decided to tender for a new community rheumatology service. One of the key performance indicators of this new service will be a monthly review of all new patients taking DMARDs (including recording disease activity scores) and being able to demonstrate that this data is being collected. It is quite a challenge in terms of manpower and IT systems to record the information and there is a penalty if the standards are not met.

Thus, the NICE guideline aims to ensure that patients receive DMARDs much more quickly and that RA is brought under control more effectively, but this may be very difficult to achieve in practice in this current economic climate.

Glucocorticoids

With regard to the use of steroids, the NICE guideline recommends that healthcare professionals:1,2

  • 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
  • offer short-term treatment with glucocorticoids for managing flares in people with recent onset or established disease to rapidly decrease inflammation.

These recommendations allow GPs to use steroids to manage flares of RA in the community. Traditionally, patients have often waited a long time to be seen in specialist care when suffering from a flare—the GP can now treat with steroids. However, it is very important that the use of glucocorticoids is communicated from primary to specialist care; perhaps a patient-held record would be a good way of ensuring that this happens.

Frequent use of steroids in primary care can mask the fact that a patient’s RA is becoming more active and they may appear to be clinically very well when they attend for review in specialist care. However, if it is clear that multiple courses of steroids have been used, then the picture is very different.

Biological drugs

Biological drugs, such as tumour necrosis factor (TNF) inhibitors and rituximab, are monoclonal antibody therapies, which act in very specific parts of the inflammatory cycle. Infliximab and etanercept were the first anti-TNF drugs. They were first used in the late 1990s (although not approved by NICE until 2002). Since then, newer TNF inhibitors have emerged, as well as other biological therapies that block different steps in the inflammatory arthritis pathway. Anti-TNFs have been reported as being rapidly effective in just over 60% of patients with RA. They are much more expensive than conventional DMARDs. Not all biological therapies have currently been deemed to be cost effective by NICE and some are therefore not available through the NHS (e.g. anakinra, abatacept). Four anti-TNF drugs have been approved by NICE (infliximab, etanercept, adalimumab, and certilizumab pegol), together with rituximab (an antibody directed against B-lymphocytes), which may be appropriate for use in patients who do not respond to anti-TNFs.

Anti-TNF therapies can interfere with the immune system, so GPs should be alert to signs of infection in patients receiving these biological therapies. Often the normal fever response is suppressed and the patient will be apyrexial, making diagnosis of infection even more difficult.10

Annual review

The NICE guideline recommends annual review for patients with RA for several purposes (see Box 1). This suggests a much more detailed annual review than is currently happening in either primary or secondary care. Traditionally, health assessment questionnaires have not been used, but it is good news that a holistic review of each patient will occur.

The cardiovascular risk of RA is also emphasised and this has not been realised until recently. It is thought that having RA confers extra cardiovascular risk similar to that of having diabetes, and risk factors, such as weight, exercise, smoking, and blood pressure should all be tackled aggressively. I do think that primary care is the best setting for this to take place as it neatly fits in with other quality and outcomes framework indicators, such as obesity and hypertension. However, there will need to be some way of sharing the data (again, perhaps with a patient-held record) or specialist care will be unable to demonstrate for its service performance indicators that a thorough and detailed annual review has taken place.

Conclusion

The NICE guideline has been well received in primary and specialist care and provides a framework around which local health economies can improve their diagnosis, referral, and treatment of patients with RA.

Box 1: Annual review of patients with rheumatoid arthritis1,2

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 co-morbidities, 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
  • assess the effect the disease is having on a person’s life

RA=rheumatoid arthritis

References

  1. National Institute for Health and Care Excellence. Rheumatoid arthritis: national clinical guideline for management and treatment in adults. Clinical Guideline 79. London: NICE, 2009. Available at: www.nice.org.uk/CG79
  2. National Collaborating Centre for Chronic Conditions. Rheumatoid arthritis: National clinical guideline for management and treatment in adults. London: RCP, 2009. Available at: www.nice.org.uk/CG79
  3. Walker D, Hall S. NICE guidance on rheumatoid arthritis: implications and challenges for rheumatologists. Rheumatology (Oxford) 2010; 49 (4): 619–620.
  4. National Audit Office. Services for people with rheumatoid arthritis. London: The Stationery Office, 2009.
  5. Arnett F, Edworthy S, Bloch D et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31 (3): 315–324.
  6. Van Aken J, Lard L, Le Cessie S et al. Radiological outcome after four years of early versus delayed treatment strategy in patients with recent onset rheumatoid arthritis. Ann Rheum Dis 2004; 63 (3): 274–279.
  7. Borg G, Allander E, Lund B et al. Auranofin improves outcome in early rheumatoid arthritis. Results from a 2-year, double blind placebo controlled study. J Rheumatol 1988; 15 (12): 1747–1754.
  8. Möttönen T, Hannonen P, Korpela M et al; FIN-RACo Trial Group. FINnish Rheumatoid Arthritis Combination therapy. Delay to institution of therapy and induction of remission using single-drug or combination-disease-modifying antirheumatic drug therapy in early rheumatoid arthritis. Arthritis Rheum 2002; 46 (4): 894–898.
  9. British Society for Rheumatology. National guidelines for the monitoring of second line drugs. London: BSR, 2000.
  10. Ding T, Deighton C. Complications of anti-TNF therapies. Future Rheumatology 2007; 2 (6): 587–597. G