Referral from primary care

1.1.1.

Refer for specialist opinion any adult with suspected persistent synovitis of undetermined cause. Refer urgently (even with a normal acute-phase response, negative anti-cyclic citrullinated peptide [CCP] antibodies or rheumatoid factor) 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 3 months or longer between onset of symptoms and seeking medical advice. [2009, amended 2018]

Investigations

If the following investigations are ordered in primary care, they should not delay referral for specialist opinion (see recommendation 1.1.1).

Conventional disease-modifying anti-rheumatic drugs

1.4.1.

For adults with newly diagnosed active RA:

• Offer first-line treatment with conventional disease-modifying anti-rheumatic drug (cDMARD) monotherapy using oral methotrexate, leflunomide or sulfasalazine as soon as possible and ideally within 3 months of onset of persistent symptoms.
• Consider hydroxychloroquine for first-line treatment as an alternative to oral methotrexate, leflunomide or sulfasalazine for mild or palindromic disease.
• Escalate dose as tolerated. [2018]

1.4.2.

Consider short-term bridging treatment with glucocorticoids (oral, intramuscular or intra-articular) when starting a new cDMARD. [2018]

1.4.3.

Offer additional cDMARDs (oral methotrexate, leflunomide, sulfasalazine or hydroxychloroquine) in combination in a step-up strategy when the treatment target (remission or low disease activity) has not been achieved despite dose escalation.[2018]

Biological and targeted synthetic DMARDs

NICE has published technology appraisal guidance on biological and targeted synthetic DMARDs for RA. For full details, see our interactive flowchart on rheumatoid arthritis.

The recommendations below are from NICE technology appraisal guidance 72. The 2009 guideline committee reviewed the evidence on anakinra and incorporated the recommendations into the guideline. The technology appraisal was then withdrawn.

1.5.1.

On the balance of its clinical benefits and cost effectiveness, anakinra is not recommended for the treatment of RA, except in the context of a controlled, long-term clinical study. [2009]

1.5.2.

Patients currently receiving anakinra for RA may suffer loss of wellbeing if their treatment were discontinued at a time they did not anticipate. Therefore, patients should continue therapy with anakinra until they and their consultant consider it is appropriate to stop. [2009]

1.5.3.

Do not offer the combination of tumour necrosis factor-α (TNF-α) inhibitor therapy and anakinra for RA. [2009]

Glucocorticoids

1.5.4.

Offer short-term treatment with glucocorticoids for managing flares in adults with recent-onset or established disease to rapidly decrease inflammation. [2009]

1.5.5.

In adults with established RA, only continue long-term treatment with glucocorticoids when:

• the long-term complications of glucocorticoid therapy have been fully discussed, and
• all other treatment options (including biological and targeted synthetic DMARDs) have been offered. [2009, amended 2018]

Physiotherapy

1.8.1.

Adults with RA should have access to specialist physiotherapy, with periodic review (see 1.9.2 and 1.9.3), to:

• improve general fitness and encourage regular exercise
• learn exercises for enhancing joint flexibility, muscle strength and managing other functional impairments
• learn about the short-term pain relief provided by methods such as transcutaneous electrical nerve stimulators (TENS) and wax baths. [2009]

Occupational therapy

1.8.2.

Adults with RA should have access to specialist occupational therapy, with periodic review (see 1.9.2 and 1.9.3), if they have:

• difficulties with any of their everyday activities, or
• problems with hand function. [2009]

Hand exercise programmes

1.8.3.

Consider a tailored strengthening and stretching hand exercise programme for adults with RA with pain and dysfunction of the hands or wrists if:

• they are not on a drug regimen for RA, or
• they have been on a stable drug regimen for RA for at least 3 months. [2015]

1.8.4.

The tailored hand exercise programme for adults with RA should be delivered by a practitioner with training and skills in this area. [2015]

Podiatry

1.8.5.

All adults with RA and foot problems should have access to a podiatrist for assessment and periodic review of their foot health needs (see 1.9.2 and 1.9.3). [2009]

1.8.6.

Functional insoles and therapeutic footwear should be available for all adults with RA if indicated. [2009]

Psychological interventions

1.8.7.

Offer psychological interventions (for example, relaxation, stress management and cognitive coping skills^[1]) to help adults with RA adjust to living with their condition. [2009]

NICE has published a guideline on depression in adults with a chronic physical health problem.

Diet and complementary therapies

1.8.8.

Inform adults with RA who wish to experiment with their diet that there is no strong evidence that their arthritis will benefit. However, they could be encouraged to follow the principles of a Mediterranean diet (more bread, fruit, vegetables and fish; less meat; and replace butter and cheese with products based on vegetable and plant oils). [2009]

1.8.9.

Inform adults with RA who wish to try complementary therapies that although some may provide short-term symptomatic benefit, there is little or no evidence for their long-term efficacy. [2009]

1.8.10.

If an adult with RA decides to try complementary therapies, advise them:

• these approaches should not replace conventional treatment
• this should not prejudice the attitudes of members of the multidisciplinary team, or affect the care offered. [2009]

Terms used in this guideline

Why this is important

Analgesics (including NSAIDs, paracetamol, opioids and compound analgesics) are sometimes used with disease-modifying treatments to relieve pain and stiffness when symptom control is inadequate. Current practice regarding the choice of analgesic in RA is variable. The evidence is limited for many of the analgesic drugs other than NSAIDs, and their relative effectiveness is unknown. Further research in this area may inform future guidance on the use of analgesic drugs other than NSAIDs for controlling symptoms.

Why this is important

All DMARDs have a slow onset of action. In some cases, response may not be seen for 2 to 3 months. In contrast, glucocorticoids have an immediate effect on joint pain and swelling. In clinical practice, several different regimens are prescribed to ‘bridge’ the time between the initial prescription of DMARDs and the clinical response. However, good quality evidence from randomised controlled trials (RCTs) demonstrating the effectiveness of glucocorticoids as bridging treatment is limited and inconclusive. Further research is needed to inform recommendations for practice regarding whether bridging treatment with steroids should be used until the new DMARD begins to take effect.

The optimal dosing strategy and mode of administration for bridging glucocorticoids also needs to be established. Although the anti-inflammatory response is dose dependent, side effects of glucocorticoids vary according to both the dose and the duration of treatment.

Why this is important

RA is a chronic inflammatory condition that needs regular review to enable adjustments in management to achieve a target of remission or low disease activity.

Although ultrasound is able to show subclinical inflammation or erosions in some people in clinical remission, evidence from RCTs does not support using ultrasound for routine monitoring. However, ultrasound may be useful for assessing disease activity in some people with RA; specifically, when clinical examination is inconclusive or is inconsistent with other signs of disease activity (for example, pain or markers of inflammation). There is no reliable evidence on the added value of ultrasound as part of a monitoring strategy in these subgroups.

In addition, when there is inconsistency between clinical examination and disease activity, it may be unclear if the person has subclinical inflammatory synovitis or more of a widespread pain syndrome, which is not inflammatory. These need very different treatments, so it is important to define them accurately.

Why this is important

Early diagnosis of RA is essential to reduce the impact of the disease on multiple systems in the body. The course of RA and the initial presentation can be highly variable; most people with RA have definite synovitis on clinical assessment, but sometimes this is not obvious, leading to uncertainty about the diagnosis. Ultrasound is a non-invasive and relatively inexpensive imaging modality that can detect subclinical synovitis and early erosive disease. It might help determine an early diagnosis of RA when the diagnosis would otherwise be uncertain. Early diagnosis enables earlier treatment, providing an opportunity to improve the longer term outcomes for people with RA. The use of ultrasound may also allow healthcare professionals to be more confident about ruling out a diagnosis of RA.

Why this is important

Current recommendations suggest all people with RA should be offered the same management; however clinical experience suggests that the condition responds less well in some people and some suffer progressive radiographic damage and impaired function despite standard management. Several factors have been identified in the literature that, if present and identified early in the course of the disease, may predict a poor prognosis (greater radiographic progression). These include anti-CCP antibody positivity and the presence of radiographic erosions at baseline. At present it is unclear whether people with poor prognostic markers should have different management early in the disease, and whether this would improve radiographic and functional (HAQ) outcomes in this group.

Why this is important

Methotrexate is an important drug in the treatment of RA. Subcutaneous administration is an alternative option for people who have side effects with oral treatment. Evidence on the effectiveness of subcutaneous methotrexate is lacking, but its effects may be superior, due to increased bioavailability, and fewer side effects than with oral drugs. Research on subcutaneous methotrexate will inform future guideline recommendations.

Why the committee made the recommendations

Evidence showed that anti-cyclic citrullinated peptide (CCP) antibodies and radiographic damage at baseline were both important prognostic factors for subsequent radiographic progression. Anti-CCP antibodies are usually measured and X-rays often taken as part of diagnosis. When this has not been done, the committee agreed that the tests should be performed as soon as possible. The results will inform discussions with the patient about how their rheumatoid arthritis (RA) might progress and reinforce the importance of active monitoring and rapidly seeking specialist care if the disease worsens.

There was limited evidence on poor function, as measured by the Health Assessment Questionnaire (HAQ), as a prognostic factor. However, the committee agreed that functional ability (measured, for example, by HAQ) should be determined at diagnosis to provide a baseline for assessing response to treatment at the annual review.

Evidence suggests that all people with RA should be offered the same management strategy; however, in the committee’s experience some people may respond less well and have more progressive radiographic damage and impaired function. Because the evidence was limited as to whether people with poor prognostic markers should follow a different management strategy to improve radiographic and functional (HAQ) outcomes, the committee agreed to make a research recommendation.

How the recommendations might affect practice

Anti-CCP antibodies are usually measured so there should be no change in current practice. X-raying the hands and feet and measuring functional ability at baseline reflects current best practice, but not everyone with RA currently has these investigations. There may be an increase in the number of X-rays, especially in units without early inflammatory arthritis clinics, but this is unlikely to have a substantial resource impact.

Measuring functional ability at baseline will involve a change of practice for some providers, but the cost is low and so this is not expected to have a substantial resource impact.

Full details of the evidence and the committee’s discussion are in evidence review B: Risk factors.

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Why the committee made the research recommendation on ultrasound in diagnosis

Ultrasound is not used widely in diagnosing RA, but use is increasing and depends on the clinic and the rheumatologist. Evidence was inconsistent and too limited for the committee to make any recommendation for or against its use in diagnosis. The committee noted that the studies generally included only people with clinically definite synovitis and agreed that ultrasound may be more useful when there is uncertainty about the diagnosis after clinical assessment. They decided to make a research recommendation to inform future guidance on who (if anyone) should have ultrasound to aid diagnosis.

Full details of the evidence and the committee’s discussion are in evidence review A: Ultrasound for diagnosis.

Return to the recommendation

Why the committee made the recommendations

How the recommendations might affect practice

A treat-to-target strategy is current best practice in most NHS settings. The 2016 National Clinical Audit for Rheumatoid Arthritis and Early Inflammatory Arthritis indicated that healthcare professionals set a treatment target for about 90% of their patients. Although the 2018 recommendation specifies a target of remission or low disease activity, rather than a disease level previously agreed with the person, the committee agreed that these are the targets commonly used and so this is unlikely to involve a significant change in practice.

Monthly monitoring was recommended in the 2009 guideline, but the committee acknowledged that many clinics do not monitor active disease this often. A regional survey (Tugnet 2013) reported that about two-thirds of people with RA received monthly CRP monitoring but only a quarter had monthly monitoring of disease activity (with about 40% in dedicated early arthritis clinics) until disease control was achieved. The committee were unsure whether these rates reflected practice across England and noted that practice had improved since the survey was conducted in 2011. However, the committee agreed that monthly monitoring would likely involve a change in practice in some clinics.

Full details of the evidence and the committee’s discussion are in evidence review C: Treat-to-target.

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Why the committee made the recommendations

How the recommendations might affect practice

The 2009 guideline recommended a combination of cDMARDs (including methotrexate and at least 1 other cDMARD) for newly diagnosed RA and emphasised the importance of starting effective cDMARD therapy as soon as possible.

The 2009 recommendation to start with combination therapy was not widely adopted. The 2016 National Clinical Audit for Rheumatoid Arthritis and Early Inflammatory Arthritis reported that only 46% of people with RA received combination cDMARDs at any time. Currently there is variation in practice regarding the choice of cDMARD(s) and treatment strategy, with many healthcare professionals preferring to start with monotherapy and only use combination therapy when response is inadequate.

The 2018 recommendations to start with monotherapy and add drugs when the response is inadequate are unlikely to have a substantial impact on practice or resources, as they align with the current approach taken by many healthcare professionals. However, the recommendations should result in a more consistent treatment strategy and reduce the number of people prescribed combination therapy on diagnosis.

The 2009 guideline recommended methotrexate as one of the first drugs used in combination therapy. The 2018 recommendations do not specify which cDMARD should be used at any stage of treatment. Again, this will be unlikely to have a significant impact on practice, and methotrexate is likely to remain one of the most commonly prescribed drugs.

The recommendations on dose escalation and reduction have not changed substantially from the 2009 guideline and reflect current clinical practice. The committee clarified that dose reduction and the use of a step-down strategy should only be considered after a person has maintained the treatment target for at least 1 year without the use of glucocorticoids.

Full details of the evidence and the committee’s discussion are in evidence review F: DMARDs.

Return to the recommendations

Why the committee made the recommendation

Evidence from RCTs on the use of short-term bridging treatment with glucocorticoids to relieve symptoms while people are waiting for a new DMARD to take effect was limited. There was some evidence that fewer people withdrew from the studies due to inefficacy or adverse events when they were taking glucocorticoids, although there was no evidence that glucocorticoids were effective in terms of disease activity score, quality of life or function, as studies did not report these outcomes. In the committee’s experience people with active arthritis may benefit from the anti-inflammatory effects of glucocorticoids. However, for others with less active disease this additional treatment may not be needed. The committee agreed that short-term glucocorticoids could be considered on a case-by-case basis.

Because of the lack of good quality evidence, the committee decided to make a research recommendation to determine the effectiveness of short-term glucocorticoids for adults taking a new DMARD, including the most effective regimen.

How the recommendation might affect practice

Most healthcare professionals offer short-term bridging treatment with glucocorticoids to adults starting a new DMARD. They can continue to offer this but the recommendation encourages them to consider whether this additional treatment is always needed. Therefore this is unlikely to result in additional spending for the NHS.

Full details of the evidence and the committee’s discussion are in evidence review H: Glucocorticoids.

Return to the recommendation

Why the committee made the recommendations

Evidence suggested that non-steroidal anti-inflammatory drugs (NSAIDs) may offer a small benefit in relieving symptoms for adults with RA (including pain and stiffness). The committee agreed that this was likely to outweigh the increase in gastrointestinal adverse events associated with NSAIDs. To minimise adverse events, the committee agreed that NSAIDs should be used at the lowest doses and for the shortest possible time, with a proton pump inhibitor, and that risk factors for adverse events should be reviewed regularly. The recommendations for analgesic treatment in this guideline replace those in the 2009 guideline.

There was limited evidence on paracetamol, opioids and tricyclic antidepressants and no evidence for nefopam, gabapentinoids or selective serotonin reuptake inhibitor (SSRI) and SSNRI antidepressants. The committee acknowledged that the 2009 guideline had recommended analgesics other than NSAIDs for pain control. However, the 2009 guideline indicated that the evidence on analgesia other than NSAIDs was ‘sparse’. No further evidence on these drugs was identified since the publication of the 2009 guideline. The committee for the 2018 guideline decided to make a research recommendation rather than a practice recommendation on analgesia other than NSAIDs.

How the recommendations might affect practice

Current practice regarding the choice of analgesic is variable, with paracetamol, compound analgesics and NSAIDs all commonly used to control symptoms. Choice of analgesic tends to be based on individual effectiveness as well as the person’s risk profile, tolerance, and side effects. In particular, there are some groups of people for whom NSAIDs are unsuitable because of contraindications, comorbidities or tolerability, and other people who are currently benefiting from analgesic drugs other than NSAIDs. The current approach is likely to continue but there may be an increase in prescribing of NSAIDs instead of other analgesic drugs for people with newly diagnosed RA.

Full details of the evidence and the committee’s discussion are in evidence review G: Analgesics.

Return to the recommendations

Why the committee made the recommendations

How the recommendations might affect practice

The frequency of monitoring and review appointments for people who have reached the treatment target vary around the country, with some people being seen more often than needed and others not receiving adequate follow-up. The 2018 recommendations are likely to reduce unwarranted variation.

Most people with RA currently have rapid access to specialist care when they have a flare. The 2016 National Clinical Audit for Rheumatoid Arthritis and Early Inflammatory Arthritis reported that 92% of people had access to urgent advice, with 97% of providers running a telephone advice line. Therefore the recommendation will not affect current practice.

Use and availability of ultrasound varies widely across the country and even between healthcare professionals in the same department. Some healthcare professionals use it routinely whereas others use it on a case-by-case basis. The recommendation should reduce the overall use of ultrasound while still allowing its use for selected subgroups.

Full details of the evidence and the committee’s discussion are in evidence review E: Frequency of monitoring.

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