Management of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic systemic disease that affects the synovial joints. Once mechanical damage has occurred, pain and joint deformity often require aids and appliances and, eventually, surgery.
The British Society for Rheumatology (BSR) has published standards of care which patients with rheumatoid arthritis should expect to receive.¹
These focus on a number of specific areas:

Patients should be referred as soon as the condition is suspected. The BSR standard is for a rheumatologist to see the patient within twelve weeks.
Early detection is now possible by laboratory diagnosis. Antibodies called anticyclic citrullinated peptides occur 10 years before the development of clinical disease. Unlike the rheumatoid factor test they are highly specific and if the test is available to GPs locally it should be performed before referral to secondary care.²

The patient should be fully involved in the multidisciplinary management of their condition and given information on self-management of their symptoms and the existence of any local support groups. The psychological, emotional, employment, and social issues relevant to the patient also need to be addressed. The needs of carers should also be considered.

Current guidance is that patients with suspected rheumatoid arthritis should be referred to a rheumatologist as soon as possible so that disease-modifying agents can be started early in the condition.³ In the interim, non-drug measures and symptomatic treatment such as simple analgesics and non-steroidal anti-inflammatories (NSAIDs) can be instituted.

Non-drug management

The core members of the multidisciplinary team will be the GP, the rheumatologist, physiotherapists and occupational therapists. Other specialties that may need to be involved include podiatrists, orthotists, dieticians, pharmacists and neurologists.

Pain clinic specialists may be able to advise on non-drug management options such as transcutaneous electrical nerve stimulation (TENS) and behavioural approaches.¹

Non-clinical issues may need the assistance of social workers, voluntary organisations, and wheelchair services.

Drug management

Treatment has shifted to earlier and more intense use of disease-modifying agents. The aim of treatment is to improve symptoms and reduce the later complications and disability. RA is an independent risk factor for cardiovascular disease, and suppressing disease activity may reduce co-morbidity.⁴

At any stage the use of simple analgesia should be considered as an adjunct. Drugs to suppress neuropathic pain, such as carbamazepine or amitriptyline, may also be beneficial.

NSAIDs. For example: ibuprofen, diclofenac, naproxen.

• NSAIDs improve symptoms and signs of RA. They are highly effective and many RA patients rely on them, but they do not slow progression or long term disability.
• NSAIDs have a rapid onset of action, but their beneficial effects are unfortunately offset by toxicity.⁵
• There are more than 30 available. The problem is deciding which preparation will be best for which patient, in terms of side-effects and potential benefits, eg the greater cardioprotective effects of standard NSAIDs compared to COX-2 drugs.⁶ The most commonly used NSAIDs are ibuprofen, diclofenac and naproxen.
• Contraindications - gastroprotective agents should be considered for patients taking nonselective NSAIDs. NSAIDs can interact with diuretics (reduced effect in renal toxicity), warfarin (risk of bleeding), lithium (toxicity) and methotrexate (marrow toxicity). See individual drug monographs.

• COX-2 selective drugs have very similar efficacy to standard NSAIDs, although patients report individual differences.
• COX-2 selective NSAIDs are more expensive and they should only be considered in patients at significant risk of gastro-intestinal bleeding with standard NSAIDS.⁷
• The CSM and European Medicines Agency have recommended that COX-2s should not be used in patients with established ischaemic heart disease, heart failure or cerebrovascular disease (and switch to alternative therapy).⁸ Care should be taken when they are used with patients with any CVD risk factors, and the drugs should be used at the lowest effective dose for the shortest period possible.

• Early intervention with DMARDs produces better outcomes, in the short term at least.⁹ They require 4 to 6 months for a full response.
• The primary aim is to establish a tolerable and effective drug regimen for each patient. Sulfasalazine or methotrexate are often used first because they may be better tolerated. If one drug does not lead to objective benefit within 3 months a different drug is tried.
• They are instituted by specialists as soon as diagnosis, progression and severity of the disease have been confirmed. "Tight control" is the aim, which means increasing the therapy whenever the disease is not fully suppressed. Several studies have now shown this gives a significant improvement in symptoms and signs.¹⁰
• Methotrexate - this is a first line DMARD with advantage of known effectiveness and long term safety.
• Sulfasalazine - this significantly reduces disease activity and joint inflammation and parenteral gold reduces disease activity and joint inflammation, and slows radiological progression.
• Oral gold (auranofin) - this is also used but is less effective.
• Other DMARDs include hydroxychloroquine, penicillamine, azathioprine, ciclosporin, cyclophosphamide, leflunomide and minocycline. All have potentially serious adverse effects which limit their usefulness.
• Contraindications - see individual drug monographs.

• A revolution has occurred in treating RA due to the realisation that the pro-inflammatory cytokine TNF-alpha plays a central role. In the last 10 years several agents have been developed that block this molecule and TNF inhibitors significantly improve symptoms, and reduce disease activity and joint inflammation.
• Infliximab (Remicade) and etanercept (Enbrel) are very effective in reducing the symptoms and signs of RA in patients who fail to respond to DMARDs and both reduce joint swelling, radiological erosions, malaise and fatigue.¹¹
• Clinical effectiveness and side-effect profiles are similar for all these drugs. All have rapid onsets of action - days to weeks.
• Contraindications and monitoring - see individual drug monographs.
• Initiation of treatment - Patients at risk of infection (those on high-dose steroids or with uncontrolled diabetes), are excluded from treatment. See also individual drug monographs.
• Complications and reasons to discontinue drug - side-effects are generally minor and tolerable, and monitoring is not required to the degree necessary with DMARDs. Severe adverse events are unusual but have been reported. TNF is a key regulator of immunity and opportunistic infections, such as tuberculosis (TB), have been reported. Reactivation of TB, worsening of demyelinating disease, suppression of bone marrow and a variety of unusual idiosyncratic side effects can occur.

Patients should be reviewed annually by a hospital specialist or GP with special interest. The review should include disease activity, any extra-articular disease, co-morbidity, and the effect of the illness on the patient's capacity to work or study, mix socially, and remain financially viable. The effectiveness and adverse effects of medication should also be reviewed.

The opinion of an orthopaedic surgeon with a special interest in rheumatoid arthritis should be sought in patients who are on maximum tolerated therapy but have uncontrollable pain and/or significant restrictions of joint movement.

Pre-pregnancy counselling

Both male and female patients require a review of their medication, as many anti-rheumatic drugs are teratogenic.

Young patients

There should be a smooth transition from paediatric to adult services, with assessment provided by specialists in paediatric and adolescent rheumatology according to the standards laid down by the British Society of Paediatric & Adolescent Rheumatology.¹²