Drs Elaine Morrison and Hilary Capell explain why the SIGN guidelines on management of early RA recommend early therapy with DMARDs

Rheumatoid arthritis (RA) affects approximately 1% of the population. It can occur at any age, and more commonly affects women than men.

The course of RA is variable and unpredictable, but for a significant number of those affected it is a severe, progressive disease resulting in persistent pain and stiffness, joint destruction, functional decline and premature mortality.1-3

The impact of a diagnosis of RA on an individual can be immense. In addition to physical problems, many suffer lost work opportunities, depression,1 stress on relationships and decreased leisure activities. The implications for society include the economic cost of care.4-6

Implicit, therefore, in the management of RA is the need for a holistic approach to patient care with access to a multidisciplinary team, including medical (GP, rheumatologist), nursing (practice nurse, rheumatology nurse specialist), professions allied to medicine (physiotherapy, occupational therapy, podiatry, dietitian), and social worker.7-8

Why was a guideline needed?

Increasing recognition that, for many patients, RA is a severe progressive disorder with a poor outcome has prompted a re-evaluation of the traditional 'treatment pyramid'. This begins with mild, mainly symptomatic measures and defers the use of disease-modifying antirheumatic drugs (DMARDs) until the disease has progressed.

However, studies have shown that bony erosions, leading to joint destruction, often occur in early disease,9-13 and that early loss of function may be irreversible. Evidence is also accumulating that early, more aggressive intervention can improve longer-term disease outcome.14

Accordingly, the clinical effectiveness of the traditional treatment pathway has been widely challenged.15–17

It seemed an appropriate time, therefore, for the Scottish Intercollegiate Guidelines Network (SIGN) to consider an evidence-based approach to the management of early RA.18

How robust is the evidence?

The management of early RA guideline development group comprised 19 individuals, including representatives from the range of health professionals usually involved in the care of patients with early RA in routine clinical practice.

The group therefore reflected the multidisiciplinary team. As well as rheumatologists, GPs, nurses and the professions allied to medicine, the group also included two patient representatives. These individuals are an important part of any guideline team, as they may bring a different perspective on healthcare issues.

Guideline development group

All SIGN guidelines are developed in a standardised, highly structured way.19 The evidence base for the early RA guideline was developed after a systematic literature search devised by the SIGN information officer in collaboration with the members of the group.

To optimise the quality of the data, mainly systematic reviews, meta-analyses, randomised controlled trials and longitudinal studies were considered. Searches were carried out on the Cochrane Library, Medline, Embase and Pascal, with a sub-search looking at the Allied & Alternative Medicine and Mantis databases. The formal search was supplemented by additional material located by group members.

The evidence base was then critically appraised using SIGN methodology,19 by the development team working in small groups.

The level of evidence allocated to a study (Table 1, below) influences the grade of recommendation that can be made about a particular aspect of disease management.

The early RA guideline introduces a revised system for grading guideline recommendations, as shown in Table 1. Details can be found on the inside front cover of the guidelines18 or on the SIGN website: www.sign.ac.uk

Table 1: Key to evidence statements and grades of recommendations
Statements of evidence
1++ High quality meta-analyses, systematic reviews of randomised RCTs, or RCTs with a very low risk of bias
1+ Well-conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias
1- Meta-analyses, systematic reviews, or RCTs with a high risk of bias

High quality systematic reviews of case control or cohort studies

High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal

2+ Well-conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal
2- Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal
3 Non-analytic studies, e.g. case reports, case series
4 Expert opinion
Grades of recommendations

At least one meta-analysis, systematic review, or RCT rated as 1++, and directly applicable to the target population; or

A body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results


A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or

Extrapolated evidence from studies rated as 1++ or 1+


A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or

Extrapolated evidence from studies rated as 2++


Evidence level 3 or 4; or

Extrapolated evidence from studies rated as 2+


Recommended best practice based on the clinical experience of the guideline development group

Development of the guideline

Within the guideline group, each member represents both their geographical area and their profession. However, they are also expected to consult with other colleagues within their discipline to ensure the widest possible range of views.

To facilitate wider consultation, a national meeting is held for all interested health professionals when the guideline is at draft stage. This allows further exchange of views and amendment of the guideline if necessary.

The revised draft is then sent out to independent expert peer reviewers who are representative of the disciplines included in the guideline. Comments received are considered before the final draft is prepared.

Gaps in the evidence

The group was acutely aware that lack of evidence does not necessarily mean lack of efficacy and there were areas where good evidence simply was not available, highlighting the need for new research initiatives. Until such new evidence becomes available, recommended best practice, based on the clinical experience of the guideline group, has been included as a 'Good practice point' in those areas where evidence is sparse.

Improving patient care

The primary aim of the guideline is to improve the clinical care of patients with early RA. Key points in both diagnosis and treatment are summarised on the Quick Reference Guide (see Figures 1 & 2, below) included with all copies of the guideline and on the SIGN website.

Figures 1&2: Quick Reference Guide
RA guideline page 1
RA guidelines page 2

Early diagnosis and referral

Early diagnosis of RA is a prerequisite for early treatment but is not always easy. Key features of both the clinical history and examination are included in the guideline (see Figure 1, above).

All patients with persisting inflammatory joint disease (of >6–8 weeks duration) who are already receiving simple analgesia and nonsteroidal anti-inflammatory drugs (NSAIDs) should be considered for specialist rheumatology opinion and DMARD therapy, preferably within 12 weeks.

Early and sustained use of DMARDs

The evidence shows that RA should be treated as early as possible with DMARDs to control symptoms, delay disease progression and reduce later disability.20–24

To be effective, DMARD therapy needs to be sustained, often over long periods, to maintain disease suppression.25,26

DMARDs in current use are discussed, both in terms of their efficacy and toxicity, in the guideline. At present, however, the evidence does not support the routine use of combination DMARD therapy in early RA.27

Targeted immunotherapy is also briefly discussed, although its place in the treatment of early RA at present is unclear.

Effective and and safe use of NSAIDs and corticosteroids

These drugs are among those most widely used in RA. Despite this, avoidable adverse effects still occur and the guideline hope to highlight ways in which these can be reduced.

NSAIDs provide symptomatic relief of pain and stiffness without influencing the course of RA. To minimise adverse effects (e.g. peptic ulcer, renal impairment), the lowest NSAID dose compatible with symptom relief should be prescribed, and should be reviewed when a good response to DMARD therapy is achieved.

Gastro-protection should be considered in patients aged >65 years and in those with a history of peptic ulcer.28,29

The evidence does not support the routine use of oral corticosteroids as there is no sustained clinical or functional benefit, but there is a high risk of cumulative toxicity with time.

Intra-articular steroid injections can be used for rapid symptomatic relief in 'target' joints.

The multidisciplinary team

The impact of the team approach can be difficult to quantify, but studies do show increased benefit to patients.7

Simple dynamic exercise has been shown to be safe and effective, while skilled occupational therapy and podiatry advice can be invaluable to those experiencing limitations in function and mobility.

Patient information

Information about both RA and its treatment needs to be provided to patients in an accessible and relevant way. This usually involves all members of the multidisciplinary team, and ideally includes both one-to-one education and written material.30, 31

In addition, many individuals find patient-led support and self-management groups helpful.32

Promoting best practice

Best clinical practice is only as good as the evidence base supporting it. SIGN guidelines serve to indicate the strength of evidence supporting particular interventions and, importantly, to highlight those areas where little or no evidence exists.

The guideline development group hopes to promote best practice in a number of crucial areas, including:

  • Prompt diagnosis of RA
  • Early and sustained use of DMARDs
  • Effective and safe use of NSAIDS and corticosteroids
  • Involvement of the multidisciplinary team at an early stage
  • The provision of adequate and accessible patient information.

However, despite the numbers of affected individuals and the costs, both personal and to society, musculoskeletal disease is not at present a priority area for the NHS in Scotland. Therefore, to be fully effective, the SIGN guidelines on the management of early RA need to be actively implemented at local level. This requires good liaison and cooperation between members of the multidisciplinary team in both primary and secondary care.

We hope this is something that can be achieved to improve the quality of care we provide to our patients.

  • Copies of Management of Early Rheumatoid Arthritis can be obtained from SIGN, Royal College of Physicians, 9 Queen Street, Edinburgh EH2 1JQ (tel 0131 225 7324) or can be downloaded from the website at www.sign.ac.uk


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Guidelines in Practice, April 2001, Volume 4(4)
© 2001 MGP Ltd
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