Dr Raashid Luqmani (left) and Dr Joanna Robson discuss the NICE guideline and the need for a multidisciplinary approach in the management of rheumatoid arthritis
The prevalence of rheumatoid arthritis (RA) in the UK is approximately 400,000,1 with 12,000 new cases being diagnosed each year.2 The overall occurrence of RA is 2–3 times greater in women than in men. The peak age of incidence for both sexes is the 70s, but the disease can develop in patients of all ages.2
Within 2 years of diagnosis, patients experience moderate disability, and after 10 years, 30% will be severely disabled.3 Approximately one third of patients with RA stop working within 2 years of onset. The total annual costs of RA in the UK are between £3.8 billion and £4.8 billion.4 Less well known, perhaps, is the reduced life expectancy 3 (equivalent to that of patients with diabetes5) chiefly as a result of cardiovascular disease (CVD).
Need for the guideline
Management of RA is complicated and best undertaken with a secondary care provider. Early referral of patients with suspected inflammatory arthritis is crucial to getting them established on effective treatment. Previous guidelines have been published on the management of RA, including those from the British Society for Rheumatology (BSR),6,7 the American College of Rheumatology8 and the European League Against Rheumatism.9 The latter focused almost exclusively on pharmacological management. The NICE guideline on The management of rheumatoid arthritis in adults provides an evidence base for current best practice and complements the BSR guideline.3,7,10 It requires the combined efforts of both primary and secondary care to provide seamless and effective management of a complex condition. This article summarises the main points relevant to GPs.
Synovitis indicates the presence of non-bony swelling of joints resulting from excessive tissue or fluid. Patients suspected of developing persistent synovitis should be referred for specialist opinion. In very active RA, synovitis is easy to detect, but in the early stages, this clinical sign can be missed by the untrained observer (and sometimes even by the trained observer). Urgent referral is indicated:3,10
- for patients who have pain in the hands and feet
- if there is multiple joint involvement
- if there has been a significant delay between onset of symptoms and seeking medical advice (?3 months).
Patients may have a normal C-reactive protein level or erythrocyte sedimentation rate, and a negative rheumatoid factor (RF) at initial presentation, but this should not preclude an urgent referral.3,10 In practice this means referring any patients who have persistent widespread pain around joints, regardless of whether or not their GP is able to detect synovitis, and irrespective of any blood test results. This may be at odds with the trend to reduce referrals to secondary care.
Testing for RF can be of value when diagnosing RA, and measuring for anti-cyclic citrullinated peptide (CCP) antibodies should also be considered. Although, RF testing is readily available in primary care, the same is not true for anti-CCP. The test for RF is more sensitive (i.e. present in 69% of patients, but found in up to 15% of the general population), whereas anti-CCP is more specific for RA (i.e. present in 67% of patients but in only 5% of the general population11) making a false positive less likely. In practice, the tests for RF and anti-CCP may cause confusion in primary care and it would be better not to rely on such measurements prior to referral in suspected cases.
Pharmacological management of rheumatoid arthritis
Disease-modifying anti-rheumatic drugs
Patients with newly diagnosed RA should be treated with a combination of disease modifying anti-rheumatic drugs (DMARDs),3,10 including methotrexate and at least one other DMARD, and short-term glucocorticoids. The aim of therapy is to reduce symptoms and limit joint damage, and improve function and quality of life. Rapid dose escalation of DMARD monotherapy is recommended in newly diagnosed patients for whom combination DMARD therapy is not appropriate.3,10
The instigation of complicated DMARD therapy is managed primarily through the rheumatology outpatient department, but GPs play an integral role in ensuring that patients who are experiencing toxic side-effects have their medications stopped, and are referred back to secondary care urgently for review.
Glucocorticoids are beneficial in newly diagnosed patients and for dealing with acute flares, to provide rapid control of symptoms. Long-term use is not recommended, unless the risks have been explained, and patients are intolerant or unresponsive to other therapies.3,10
Tumour necrosis factor-alpha inhibitors
The NICE guideline on the management of RA also contains a section on the use of other treatments from related technology appraisals.3,10,12,13 Tumour necrosis factor-alpha (TNF-?) inhibitors are recommended for patients with active disease, who have not responded to treatment with at least two DMARDs, including methotrexate (unless contraindicated).12
Introduction of these biological therapies (adalimumab, etanercept, and infliximab), should be supervised in secondary care. Although adalimumab and etanercept can be used as monotherapy, it is common practice to enhance the effect by adding methotrexate.12 It is necessary to always use methotrexate with infliximab. In clinical practice, if methotrexate is contraindicated, many rheumatologists will prescribe an alternative DMARD in combination with anti-TNF-? therapy.
The use of biological therapy is dependent on achieving an adequate and sustained clinical response at 6 months following initiation of therapy. Switching between anti-TNF-? agents is indicated in patients who experience toxicity, rather than for inefficacy.12
Around 50% of patients with RA who do not improve with anti-TNF-? therapy will respond to rituximab, a biological treatment directed against B cells.14 The use of rituximab in combination with methotrexate is recommended by NICE for those adults with severe active disease if they have had an inadequate response to, or are intolerant of other DMARDs—this should include at least one TNF-? inhibitor.13
Management of patients with RA who fail to respond to treatment with rituximab is much more difficult, and there are no current NICE recommendations for this situation. In clinical practice, further therapies include less commonly used DMARDs, combinations of previously used DMARDs, or more experimental therapies—usually on a named-patient basis, or as part of a clinical trial. It is important that GPs are aware of these options so that they can support patients who do not respond to conventional therapy.
Ongoing symptoms are an indication for reassessment and potential increase in dose, or additional DMARD or biological therapy.3,10 This means that if a GP feels a patient is not improving or is deteriorating while on treatment, they should be referred to secondary care for reassessment.
Non-steroidal anti-inflammatory drugs (NSAIDs) should be co-prescribed with proton pump inhibitor cover for symptom relief using the lowest effective dose for the shortest possible time. If patients are already taking aspirin, pain relief should be with alternate analgesia (avoiding use of NSAIDs).3,10
Multidisciplinary team management
Patients with RA should have early and ongoing access to a multidisciplinary team (MDT). Periodic assessments should be carried out, with particular emphasis on pain, fatigue, everyday activities, mobility, ability to work, taking part in social or leisure activities, quality of life, mood, and impact on sexual relationships. The patient’s GP is well placed to explore some of these issues. A named member of the MDT should take responsibility for coordinating the patient’s management and facilitating access to care.3,10 The key priorities for primary and secondary care in the management of RA are shown in Table 1.
Patients are encouraged to exercise regularly, unless joints are acutely inflamed, in which case joint protection is recommended.3 Specialist physiotherapists can advise on exercises to enhance joint flexibility and muscle strength, and to manage functional impairments. They can also provide transcutaneous electrical nerve stimulators and wax baths for short-term pain relief.3,10 Occupational therapists should review patients soon after diagnosis and periodically thereafter, especially if they have difficulty with everyday activities or with hand function. The therapists can offer relaxation techniques, stress management, and cognitive coping skills to help patients to adjust to living with RA.4 Podiatry should be readily accessible, with provision of functional insoles and therapeutic footwear if needed.3,10
Table 1: Key priorities for implementation of the NICE guideline on RA
|Primary care||Secondary care|
|Aggressive early treatment||Yes|
|Close monitoring of disease activity for aggressive early management||Yes|
|Multidisciplinary team care||Yes|
|Monitoring for co-morbidity and identifying risk factors for CVD||Yes||Yes|
|RA=rheumatoid arthritis; CVD=cardiovascular disease|
Patients should be provided with both verbal and written information at diagnosis, to improve understanding of the disease and its management.3,10 Ongoing education, from GPs and the MDT, is crucial to empower patients to contribute to the management of their RA. All treatment options should be explained, including risks and benefits. It is important that patients are able to discuss their condition throughout the course of the disease and agree with all aspects of their care.3,10
Monitoring patients with RA
Monthly measurement of disease activity (typically using disease activity score [DAS28]) in patients with recent-onset RA allows for more aggressive treatment leading to substantially better outcomes.3,10 As a recommendation for management of RA, this is a departure from current practice and may impose a significant increase in workload on the secondary care providers. In turn, this will have implications for purchasers. Monitoring for drug toxicity is essential if using DMARDs, but local service resources will need to determine where the testing is performed (in terms of primary or secondary care).
Annual review is recommended to assess disease activity and damage, once the condition is stable.4 The review should focus on co-morbidities that can be treated, including CVD risk factors, osteoporosis, and depression. Shared responsibility between primary and secondary care can address these co-morbidities. It is likely that arrangements for annual review will depend on the availability of resources. Individual components of an annual review, such as blood-pressure measurement and cardiovascular risk monitoring may be better undertaken in primary care, whereas assessment of disease activity and complications, such as vasculitis, and disease of the cervical spine, lungs, or eyes,3,10 are best performed in secondary care. Appropriate referral to other members of the MDT is easier to carry out in secondary care. A rheumatology practitioner, commonly a specialist rheumatology nurse or physiotherapist working in secondary care, is in a good position to coordinate annual reviews.
Indications for referral for surgery
Early referral for surgery should be considered for patients in whom the following has not responded to appropriate non-surgical treatment:3,10
- persistent joint pain
- worsening function
- progressive deformity
- ongoing localised synovitis.
Complications such as imminent or actual tendon rupture, nerve compression (e.g. carpal tunnel syndrome), and stress fractures should be referred promptly to a specialist surgeon. The benefits of surgery are primarily pain relief, improvement or prevention of further deterioration of joint function, and prevention of deformity.3,10
Patients with suspected cervical myelopathy should be referred urgently for a magnetic resonance imaging scan and neurosurgical opinion. Patients with suspected or proven septic arthritis should be referred urgently for combined surgical and medical management.3,10
Diet and complementary therapies
There is no evidence of long-term benefit from any specific diet or from complementary medicine. Complementary medicine may provide short-term symptom relief, and a Mediterranean diet may help to reduce the increased CVD risk that these patients are known to have.3,10
Rheumatoid arthritis has the potential to cause widespread, permanent joint and soft tissue damage, significant disability, and reduction in quality of life, and can also result in premature death. The key recommendations from the new NICE guideline on RA are:
- early referral
- aggressive early treatment
- monitoring in newly diagnosed patients
- attention to potential complications and reversible CVD risk factors.
A multidisciplinary approach offers the best management of RA in primary and secondary care. The GP has a key role in identifying patients with suspected RA in order to facilitate rapid access to secondary care. Subsequently, GPs often administer DMARDs and monitor for toxicity. Once the disease is well controlled, the GP’s role, in partnership with secondary care, also includes screening for, and treatment of co-morbidities.
NICE implementation tools
NICE has developed the following tools to support implementation of its guideline on Rheumatoid arthritis: the management of rheumatoid arthritis in adults. They are now available to download from the NICE website: www.nice.org.uk
National cost reports and local cost templates for the guideline have been produced:
The slides are aimed at supporting organisations to raise awareness of the guideline and resulting implementation issues at a local level, and can be edited to cater for local audiences. This information does not supersede or replace the guidance itself.
Audit support has been developed to support the implementation of the NICE guideline on rheumatoid arthritis. The aim is to help NHS organisations with a baseline assessment and to assist with the audit process, thereby helping to ensure that practice is in line with the NICE recommendations. The audit support is based on the key recommendations of the guidance and includes criteria and data collection tools.
- Symmons D, Turner G, Webb R et al. The prevalence of rheumatoid arthritis in the United Kingdom: new estimates for a new century. Rheumatology 2002; 41 (7): 793–800.
- Symmons D, Barrett E, Bankhead C et al. The incidence of rheumatoid arthritis in the United Kingdom: Results from the Norfolk Arthritis Register. Br J Rheumatol 1994; 33 (8): 735–739.
- 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
- Pugner K, Scott D, Holmes J et al. The costs of rheumatoid arthritis: an international long-term view. Semin Arthritis Rheum 2000; 29 (5): 305–320.
- Pincus T, Gibofsky A, Weinblatt M et al. Urgent care and tight control of rheumatoid arthritis as in diabetes and hypertension: better treatment but a shortage of rheumatologists. Arthritis Rheum 2002; 46 (4): 851–854.
- Luqmani R, Hennell S, Estrach C et al. British Society for Rheumatology and British Health Professionals in Rheumatology guideline for the management of rheumatoid arthritis (the first two years). Rheumatology 2006; 45 (9): 1167–1169.
- Luqmani R, Hennell S, Estrach C et al. British Society for Rheumatology and British Health Professionals in Rheumatology guideline for management of rheumatoid arthritis (after the first 2 years). Rheumatology 2009; 48 (4): 436–439.
- Saag K, Teng G, Patkar N et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 2008 59 (6): 762–784.
- Combe B, Landewe R, Lukas C et al. EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2007; 66 (1): 34–45.
- 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
- Nishimura K, Sugiyama D, Kogata Y et al. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann Intern Med 2007; 146 (11): 797–808.
- National Institute for Health and Care Excellence. Adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis. Technology Appraisal 130. London: NICE, 2007. Available at: www.nice.org.uk/guidance/TA130
- National Institute for Health and Care Excellence. Rheumatoid arthritis (refractory)—rituximab. Technology Appraisal 126. London: NICE, 2007. Available at: www.nice.org.uk/guidance/TA126
- Cohen S, Emery P, Greenwald M. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 2006; 54 (9): 2793–2806.G
- The NICE guideline is likely to increase demand on rheumatology outpatient services as it encourages GPs to refer all possible new cases for assessment
- Commissioners should identify this within their capacity plans with local specialist providers and commissioning budgets
- Employing rheumatology specialist practitioners in the community, but with agreed contractual links to specialist teams, could be cost effective
- Tariff charges for rheumatology outpatients:1
- £238 (new)
- £273 (new multi-professional contacts)
- £98 (follow up)