Management of RA - summary of NICE guidance

Management of Rheumatoid Arthritis

Rheumatoid arthritis is an 'inflammatory' arthritis. The synovium becomes much thicker and changes its character such that the inflammatory cells produce cytokines and metabloproteinases which cause cartilage destruction and secondary joint damage. Joints affected by rheumatoid arthritis often become unstable causing deformities, for example of the hand.

Rheumatoid arthritis (RA) is the most common cause of inflammatory joint disease and has a prevalence of 1-2% world-wide.1 It can present in a variety of ways and the diagnosis may not be clear at the initial presentation. Investigations performed early in the disease may be negative and misleading. Recent evidence suggests that the early use of disease-modifying antirheumatic drugs (DMARDs) in the management of patients with RA slows down the progress of the disease and so it is important to identify patients early.

It commonly affects younger women aged 20 to 50 years. The diagnosis of RA is not always easy to make. However, if a patient is suspected to have the condition he or she should, in most cases, be considered for treatment to slow down the progression of the disease. This often requires an urgent referral to a rheumatologist. Unfortunately, rheumatology waiting times are notoriously long. Some departments have a policy of fast-tracking patients with evidence of recent diagnosis of RA so that they are seen quickly. This should reduce the morbidity associated with this potentially disabling disease.

Presentation

Rheumatoid arthritis is best thought of as a systemic disease as there are a number of extra-articular features. However, patients will present with painful stiff joints. Patients will usually complain of painful, tender, swollen joints that are stiff in the morning. They may complain that it takes time for them to get going in the morning, the stiffness easing as activity increases.

Differential diagnosis

It is helpful to ask oneself a series of questions to make the diagnosis.

The American College of Rheumatology criteria for the diagnosis of rheumatoid arthritis are that four of seven of the following criteria must be present:

  1. Morning stiffness in and around joints, lasting more than 1 hour.
  2. Arthritis of three or more joint areas involved simultaneously.
  3. Arthritis of at least one area in a wrist, metacarpal or proximal interphalangeal joint.
  4. Symetrical arthritis involving the same joint areas.
  5. Rheumatoid nodules.
  6. Positive serum rheumatoid factor.
  7. Radiological changes typical of RA on hand and wrist x-rays.

Guidelines that are used for a group of patients are never absolutely reliable for the diagnosis of rheumatoid arthritis in the individual patient.

When considering rheumatoid arthritis useful diagnostic tests include:

Assessment

The assessment of patients with rheumatoid arthritis requires "a basket" of measures. We do not have one figure that gives a global impression of disease activity and prognosis. The most accepted outcome measures used in clinical trials are derived from OMERACT 1 Conference (J Rheumatol 1994 21 (supplement 41) 86-9). These include the American College of Rheumatology Core Outcome measures.

Improvement can be documented and an ACR 20% improvement incorporates 20% of tender and swollen joints and 3 of the 5 remaining core outcome measures. Outcome measures at 50% improvement can be similarly estimated. A minimum improvement on a DMARD would be 20% and an acceptable improvement may be 50%. There are separate criteria for remission, which is unfortunately uncommon.

DAS28 disease activity score

The DAS28 provides you with a number on a scale from 0 to 10 indicating the current activity of the rheumatoid arthritis of your patient. A DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6 (comparable to the ARA remission criteria).

DAS28 disease activity score - information

  1. The number of swollen joints should be assessed using 28-joint counts (tender28)
  2.  The number of tender joints should be assessed using 28-joint counts (swollen28).
  3. The ESR/CRP should be measured
  4. The patients general health (GH) or global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm (both are useable for this purpose) must be obtained. ie 0-100

DAS28 calculator

 

Management

  1. Principles of Management
    • In patients with early arthritis it is important to make a diagnosis as soon as possible. Sometimes it is not possible to make a diagnosis at one visit. There should be continuing synovitis over 6 weeks. Review tests and think again at 6 weeks.
    • When the diagnosis has been made a standardised initial assessment is needed to determine the patient's disease severity and whether or not they need therapy with a DMARD. A DMARD should be used
      1. When there is continuing inflammatory disease
      2. When there is systemic features
      3. When there is laboratory evidence of active disease eg ESR, CRP
      4. Before the patient has develpoed erosions within their joints.
    • The goal of treatment should be disease remission; this is the complete cessation of inflammatory synovitis and general ill health with no swollen or tender joints, no joint pain, no stiffness and no malaise. However, this is rarely achieved. More realistic goals are the control of significant inflammatory synovitis, improvement of functional impairment and reduction of joint damage. The available evidence suggests that current therapy reduces synovitis and improves function but has limited effects in reducing radiological damage.
    • Patients need regular follow-up: this should be shared between family doctors and rheumatologist with appropriate protocols.
    • When to refer
      • Rheumatology emergencies
        These require referral within one to 2 days by direct contact with a rheumatology department. In some cases an orthopaedic department or general medical admission unit may be appropriate for initial assessment .
        • Septic arthritis - an acute exacerbation, usually affecting one joint, which is out of proporation to general rheumatology disease. The index of suspicion should be low, early aspiration of the joint is essential. The BSR guidelines recommend blood culture as well as synovial fluid culture. Patients may be systemically unwell, but this may not always be the case, notably if the patients are taking continued doses of steroids.
        • Cervical myelopathy - often an insidious progression, causing poor function. It may be difficult to distinguish from an exacerbation of rheumatoid arthritis. Cervical myelopathy is often seen in patients with severe long standing disease. Neurological examination may often be difficult because of joint deformities. Patients complain of weakness and numbness, often in a glove and stocking distribution and a story of neck pain a common form of presentation. Referrals should be to a rheumatology department, neurosurgery department or general medical department for initial assessment.
      • Urgent referrals
        These need to be made within about a week. They include systemic extra articular complications of disease such as:
        • Vasculitis
        • Mono-neuritis multiplex
        • Scleromalacia perforam
        • Scleritis
      • Complications of disease and drugs
        This may require emergency or urgent referral, depending on the nature of the condition, include:
        • Gastrointestinal bleed
        • Thrombocytopoenia/neutropoenia/pancytopoenia
        • Anaemia
        • Proteinuria
        • Mouth ulcers
        • Dyspnoea
        • Hepatitis
        • Rashes
        • Muscle weakness
        • Renal failure - chronic or acute
      • Problems with Diagnosis
        The diagnosis of rheumatoid arthritis can sometimes be difficult to make and sometimes requires time, as discussed above. If the General Practitioner is in doubt of the given diagnosis and the appropriateness of DMARD therapy, then referral to a rheumatologist may be useful.
      • Problems with Management
        If patients are not responding to treatment, or have particular problems the General Practitioner is not confident to manage, then referral to a rheumatology department is appropriate. General Practitioners may only have very few patients taking any particular DMARD, and if they are not confident in the indications, management or monitoring of these drugs in practice, then referral and shared care may be appropriate.
  2. Management of established rheumatoid arthritis
    • Drugs used in management include
      1. None
        For some patients with inactive disease by clinical and laboratory means it may be appropriate for them to take no medication.
      2. Analgesics
        Commonly used and are a useful group of drugs in patients with rheumatoid arthritis. They can be taken regularly for long-term pain. These can be added to more specific anti inflammatory medication. They may be useful for pain disturbing sleep at night. Drugs to consider include paracetamol or codeine analogues. For pain at night Amitriptyline in low doses may be helpful.
      3. Non steroidal anti inflammatory drugs
        These are useful for both analgesic and anti-inflammatory affect. Most patients will have some benefit from a drug such as Ibuprofen, Diclofenac or Naproxen. The drugs should always be taken with food. Potential side effects of these NSAID medications include the development of stomach and duodenal ulcers, although there are some medications designed to reduce this risk. It is important to inform patients of potential side effects so that they can report them and have their medication reduced or stopped so that they are at less risk of gastrointestinal haemorrhage. If patients are not able to tolerate NSAIDs because of gastrointestinal side effects, consider appropriate treatment of the gastrointestinal pathology using analgesics alone, or using an anti-inflammatory drug which may be less likely to cause upper GI side effects e.g. Nabumetone, Etodolac, Aceclofenac. For those whose quality of life is poor without NSAID but at risk of GI upset Misoprostol or a PPI should be considered. Anti-inflammatory drugs may also cause CNS side effects, rashes and, rarely in the elderly, acute renal failure.
      4. Specific Cox 2 Inhibitors
        These have recently been introduced and include Rofecoxib.
      5. DMARD
        It is now recognised that both functional and irreversible joint damage commonly occur within the first 2 years of the disease and contribute substantially to long-term disability. DMARDs are thought to interfere with the release of cytokines by activated T lymphocytes and so suppress the inflammatory disease process. These drugs have been shown to reduce the rate of erosive change in patients with RA. They are therefore being used at an earlier stage in the disease than in the past so as to impede its early progress. Recent guidelines from the American College of Rheumatology recommend that DMARD therapy should not be delayed beyond 3 months for any patient with an established diagnosis who in spite of adequate treatment with NSAIDs has ongoing signs of active disease. In addition, there is evidence that consistent use of DMARDs may reduce long-term disability by 30%. However, it is not possible to predict which patient will respond to which DMARD, Sulfasalazine or Methotrexate appear to be good first choices on current evidence.
        At present they are usually used singly. A second agent may be added. A combination of drugs may be used earlier in the illness. These drugs are very effective but have some serious side effects in some people. They have a significant lag of 2 to 6 months before we may see benefit, and if patients have side effects, the side effects may persist or deteriorate for this period after the drug has been stopped. They must be closely monitored.
        • Sulfasalazine
        • Methotrexate is now well established in the treatment of rheumatoid arthritis. More patients stay on Methotrexate for longer periods than other drugs of this group.
        • Sodium Aurothiomalate or IM gold injections are still effective in controlling disease for many people.
        • Ciclosporin is usually limited by effect on renal function, which may be irreversible.
        • Penicillamine appears to be less effective than some other drugs of this group. Azathioprine is also used less.
        • Hydroxychloroquine Sulphate is now usually used either in combination with other drugs such as Methotrexate, or for patients with other auto immune connective tissue disorders.
        • Leflunomide is expected in the near future as a similar drug in this group, which may be used in combination with Methotrexate.
        • Combinations: sometimes a second drug is added for patients whose disease is partially controlled with one drug.
        • Steroids: there is controversy regarding the use of low dose steroids in patients with early disease. There is evidence that they do reduce the rate of erosions, but there is concern concerning their long-term side effects (the difficulty in weaning patients off short-term courses of prednisolone; the long-term side-effects, eg osteoporosis; the instance of side effects is less if patients are taking less than 7.5mg per day). Steroids have a rapid effect on the management of patients with rheumatoid arthritis and may be used to cover an acute flare to manage the patient for an important social occasion or to improve the patient's quality of life whilst we are awaiting for a DMARD to be effective. In the latter use, 80 to 120 mg of Depo-Medrone IM will often have an anti-inflammatory effect for approximately 6 weeks. Intra-articular injections of steroid are useful to control inflammation that predominantly affects one or 2 joints, most often the knee and shoulder.
        • Other therapies: anti TNF receptor antibodies are expected in the near future. These are parenteral and expensive, but appear to have a rapid effect on symptoms, although long term effects are not yet established.
    • Other management actions necessary, including lifestyle and referral to other agencies.
      Multidisciplinary care
      The successful management of patients with RA relies on liaison between professionals of different disciplines. A holistic approach to the patient's condition is desirable. Much of this liaison will occur at GP level but rheumatology input may be involved. Liaison between primary and secondary care is important. Ready access to occupational therapy, chiropody and orthotics reduces the time spent on, and the necessity for secondary care consultations.
      • Advice, education
        Rheumatoid Arthritis responds well to intervention. Moreover studies by Lorig and her colleagues suggest that increased patient involvement in the management of the disease, through improved education, self-management programmes and support networks has a positive effect on outcomes. The public needs to know how to stay healthy in order to reduce, where possible, the risk of developing disease. This may, include adopting a healthier lifestyle through better diet and exercise. The public also needs to know how to access help when symptoms of arthritis develop.
      • Physiotherapy
      • Physical measures such as exercise and physiotherapy are essential to maintain the range of movement in joints and to keep muscles as strong as possible. A regular exercise programme designed to suit the patient is an essential aspect of pain management and will enhance feelings of well being.
      • Occupational Therapy
        Occupational therapy can provide advice about joint protection although the evidence for the long-term effect is lacking. Occupational therapy is important as it can help the environment become more 'user-friendly'. In other words, aids can be obtained to help turn on taps, open doors and put on clothing.
      • Social Services
        The Care Management system is appropriate for people with advanced disabling disease. There may be the need to improve the patient's environment with the installation of stair lifts, bath aids
      • Chiropody
      • Orthotist
        Appropriate, comfortable, supportive footwear (if carefully made) can eliminate pain when walking.
      • Surgery
        Hip replacement and knee replacement surgery has been one of the major advances in the past 15 years for people with arthritis. These operations are now performed quickly, with short periods of hospitalisation. While all operations can have complications, problems are becoming less common. Patients with multiple joint problems will benefit from the opinion of an orthopaedic surgeon interested in rheumatoid arthritis. The aims of surgery are primarily to relieve pain and secondary to restore function. Indications for urgent treatment are septic arthitis and compression of nerves and spinal cord.
        • Replacement arthroplasty
        • Excision arthroplasty
        • Arthrodesis (less common) e.g. ankle, pip joints
        • Cervical fusion for subluxation (rare)
        • Synovectomy in joints not damaged to prevent disease (no evidence yet).
        • Ruptured tendons
      • Psychology
        The development of arthritis can cause depression. Patients may mourn for their loss of health and become frustrated when performing tasks that were easy before. The lethargy and tiredness common in severe arthritis can make any depression worse. If the patient can come to terms with these feelings of depression, the arthritis often becomes easier to manage and certainly easier to live with. To overcome negative feelings ask the patient to try and develop:
        1. a positive attitude
        2. an exercise programme (particularly swimming). Get the patient to start with an exercise they enjoy.
        3. a change of lifestyle, including a sensible diet to control weight, reducing the load on damaged joints.
        4. a pain management plan that will help the patient learn how to manage pain and stress in a positive way
      • Alternatives
        When it comes to the treatment of rheumatoid arthritis, everyone seems to have a pet cure. These cures vary from reflexology, naturopathy, homeopathy and dietary restrictions to massage and chiropractic. Virtually all patients who develop arthritis will try one or more of these remedies looking for a miracle cure. Miracle cures are rare indeed and there is very little scientific evidence to back these forms of therapy. However, it is also fair to say that in the majority of cases these forms of therapy are not harmful. A good nutritious diet, regular massage and some vitamin supplements may well make you feel better even if they rarely cure arthritis.

Monitoring

Disease Modifying Antirheumatic Drugs (DMARDs) playa key role in the treatment of rheumatoid arthritis. All are potentially toxic and regular monitoring for toxicology is necessary.

Azathioprine
Ciclosporin
IM gold
Oral gold
Methotrexate
Penicillamine
Sulfasalazine