Management of rheumatoid arthritis: summary of NICE guidance

This is one of a series of BMJ summaries of new guidelines, which are based on the best available evidence; they highlight important recommendations for clinical practice, especially where uncertainty or controversy exists.

## Referral, diagnosis, and investigations
- Refer for specialist opinion anyone with suspected persistent synovitis of undetermined cause. Refer urgently even if blood tests show a normal acute-phase response or negative rheumatoid factor and if:
-The small joints of the hands or feet are affected -More than one joint is affected, or -There has been a delay of three months or longer between symptom onset and seeking medical advice.
[Based on high and moderate quality observational studies of early prognosis and identification or diagnosis] - Offer to test for rheumatoid factor in people with suspected rheumatoid arthritis who have synovitis. [Based on high and moderate quality early identification observational studies]
- Consider measuring anticyclic citrullinated peptide antibodies in people with suspected rheumatoid arthritis if: -They are negative for rheumatoid factor, and -Combination therapy is being considered (see section on disease modifying antirheumatic drugs).
[Based on data from case series] - X ray the hands and feet early in people with persistent synovitis in these joints.[Based on high and moderate quality early identification studies]

## Communication and education
- Offer verbal and written information to people with rheumatoid arthritis to: -Improve their understanding of the condition and its management, and -Counter any misconceptions they may have.
- For those wishing to know more, offer participation in existing educational activities, including self management programmes.
[Both recommendations are based on high and moderate quality meta-analyses, randomised controlled trials, and the GDG's opinion]
The multidisciplinary team

## Non-steroidal anti-inflammatory drugs
- When offering an oral NSAID or COX 2 inhibitor, the first choice should be either a standard NSAID or a COX 2 inhibitor (other than etoricoxib 60 mg) at the lowest effective dose for the shortest possible time. In either case, coprescribe a proton pump inhibitor with the lowest acquisition cost.
- All oral NSAIDs and COX 2 inhibitors have analgesic effects of a similar magnitude but vary in their potential gastrointestinal, liver, and cardiorenal toxicity; therefore, when choosing the agent and dose, consider the individual's risk factors, including age. When prescribing these drugs, consider appropriate assessment and/or monitoring of these risk factors.
- If a person with rheumatoid arthritis needs to take low dose aspirin, consider other analgesics before substituting or adding an NSAID or COX 2 inhibitor (with a proton pump inhibitor) if pain relief is ineffective or insufficient.
- If NSAIDs or COX 2 inhibitors are not providing satisfactory symptom control, review the regimen for disease modifying or biological drugs.
[ For people with established disease (longer than two years)
- If disease is stable, cautiously reduce dosages of disease modifying or biological drugs; return promptly to disease controlling doses at the first sign of a flare-up.
- When introducing new drugs to improve disease control, consider decreasing or stopping an individual's pre-existing rheumatological drugs once the disease is controlled.
- If doses of disease modifying or biological drugs are being decreased, or the drugs are being stopped, arrange for prompt review.
[ the patient with the knowledge, skills, and resources to minimise the effects of the disease.

## Further information on the guidance
A wealth of guidance is now available on the diagnosis, investigations, and treatment of rheumatoid arthritis. Treatment aims to control pain and inflammation and to reduce joint damage, disability, and loss of function, thereby improving quality of life. This latest NICE guideline includes a combination of pharmacological and non-pharmacological interventions but also highlights the importance of early diagnosis and intervention. It draws on the most up to date evidence and pulls together areas covered in existing guidance [bib_ref] British Society for Rheumatology and British Health Professionals in Rheumatology guideline for..., Luqmani [/bib_ref] and in the NICE technology appraisals. 9-13 Its aim is to improve the quality of life of patients and to reduce variation in practice, such as drug sequencing, choice and combination of disease modifying antirheumatic drugs, and access to, and interventions provided by, the multidisciplinary team.

# Methods
The guideline was developed using current NICE guideline methodology,which involved systematic literature searches and critical appraisal and summarising of evidence. A Guideline Development Group (GDG) discussed the evidence and formulated the clinical recommendations. The GDG comprised people with rheumatoid arthritis as well as healthcare professionals representing a typical multidisciplinary team, both in primary and secondary care, and invited experts when additional expertise was required. The supporting technical team included those with specific expertise in literature search techniques, systematic evidence review, health economics, and project management.
The GDG accepted a clinical diagnosis of rheumatoid arthritis as being more important than the 1987 American Rheumatism Association's classification criteria for rheumatoid arthritis. [bib_ref] The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid..., Arnett [/bib_ref] This is because an early persistent synovitis in which other disease has been ruled out needs to be treated as if it is rheumatoid arthritis to try to prevent damage to joints. International committees are currently examining the diagnostic criteria for early rheumatoid arthritis.
The GDG categorised rheumatoid arthritis into two categories: recent onset (disease duration of up to two years) and "established" (disease duration of longer than two years). Within recent onset disease, categories of suspected persistent synovitis or suspected rheumatoid arthritis refer to patients in whom a diagnosis is not yet clear but in whom referral to specialist care or further investigation is required.
The recommendations on NSAIDs replace the rheumatoid arthritis aspects only of NICE's 2001 technology appraisal on cyclo-oxygenase-2 (COX 2) selective inhibitors.All the recommendations (except the last one) in the latest guidance on rheumatoid arthritis are taken from NICE's 2008 osteoarthritis guideline,which updated the guidance on COX 2 selective inhibitors and NSAIDs. This was done because the GDG believed that the results of the extensive cost effectiveness modelling for the osteoarthritis guideline were unlikely to differ for rheumatoid arthritis.
Health economic evidence was reviewed to evaluate whether guideline recommendations would be a cost effective use of healthcare resources. The evidence comprised published economic analyses, which compare costs and benefits (in terms of quality adjusted life years) between two or more interventions. Where health economic evidence was limited, the guideline process allowed the health economist from the GDG to develop a new economic evaluation-for example, in evaluating the use of combinations of disease modifying antirheumatic drugs and steroids in patients with early disease. The model is described in detail in the full NICE guideline. 2
The guideline was subject to a web based, external consultation from stakeholders. This drew 415 submitted comments, each of which was considered by the GDG for its validity and usefulness, and where deemed appropriate the guideline was modified in the light of these.
NICE has produced four different versions of the guideline: a full version; a quick reference guide; a version known as the "NICE guideline" that summarises the recommendations; and a version for patients and carers. All these versions are available from the NICE website (www.nice.org.uk/ CG79).

## Additional recommendations: biological drugs
It was part of the remit of the GDG to re-evaluate the information outlined in NICE's technical appraisal on anakinra [bib_ref] The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid..., Arnett [/bib_ref] and incorporate updated information in the new guideline, but after reviewing the evidence on anakinra, the GDG made no changes to the recommendations. The GDG also had a remit to incorporate the information on other biological drugs outlined in the NICE technical appraisals. 9-13 - On the balance of its clinical benefits and cost effectiveness, anakinra is not recommended as a treatment for rheumatoid arthritis, except in the context of a controlled, long term clinical study. If patients are already receiving anakinra, continue this until they and their consultant consider it is appropriate to stop. [Based on a NICE technical appraisal- Do not offer the combination of tumour necrosis factor- inhibitor therapy and anakinra. [Based on high and moderate quality meta-analyses and randomised controlled trials]

# Future research
The exercise of developing guidelines on managing rheumatoid arthritis drew attention to enormous gaps in the knowledge of the GDG. Several areas not covered by the literature remain to be evaluated. Recognising early synovitis is not always straightforward, and clinical skills alone are not always reliable. Thus the cost effectiveness of more objective tests such as magnetic resonance imaging, ultrasonography, and testing for anticyclic citrullinated peptide antibodies needs to be examined in establishing the diagnosis and prognosis of small joint synovitis. Although the treatment of early active disease has to be aggressive, the role of disease modifying antirheumatic drugs (and the effect of symptom duration on patient outcomes) in the treatment of mild rheumatoid arthritis should be assessed. The cost effectiveness of early management with biological drugs (before the failure of two conventional disease modifying antirheumatic drugs) should be assessed to determine if this could be a cost effective strategy in subgroups of patients with rheumatoid arthritis. As more patients are exposed to biological therapies, research needs to determine the most appropriate treatment strategy if a first tumour necrosis factor- inhibitor fails.
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