memo & hrc
About FAST

Gout is a metabolic disorder characterised by sudden and very severe attacks of pain, swelling and inflammation in the joints of the feet, knees, ankles, hands and wrists – and especially in the big toes. It has become the commonest type of inflammatory arthritis, affecting 1-2% of all people seen by doctors in General Practice. Men are much more frequently affected and gout rarely develops in women before the menopause. It is, however, age-related in both sexes and its prevalence rises to more than 7% in men and 3% in women over the age of 75 years. Gout is not infrequently associated with other medical disorders such as obesity, hypertension, hyperlipidaemia, diabetes, strokes, angina, heart attacks and kidney disease.

What causes gout? Gout develops as a result of a prolonged increase in the concentration of uric acid (urate) in the blood and tissues. This is medically described as hyperuricaemia. Uric acid is a normal end product of the breakdown and turnover of the cells of the body, but is also derived from foods in the diet. Most patients with gout have high levels of urate in their blood because of an inherited inability to increase the quantity of uric acid passed out through the kidneys when the consumption of certain foods is increased. Less commonly hyperuricaemia is caused by drugs such as diuretics (water tablets) or alcohol which interfere with kidney function; and rarely by conditions that result in increased production of uric acid. Acute attacks of gout occur when needle-like urate crystals, which have formed in tissues saturated with uric acid, are shed into joints and provoke intense pain and inflammation. Hyperuricaemia is the most important risk factor for the development of gout but the majority of people with raised blood levels of urate remain free from pain or other symptoms of gout (asymptomatic hyperuricaemia), and most will never develop gout. People destined to develop gout do, however, go through an initial phase of asymptomatic hyperuricaemia which may last months or years before they suffer their first attack. Two thirds of patients experience a second attack of painful gouty arthritis within one year and if the underlying hyperuricaemia is left untreated intermittent flares of acute gouty arthritis become more frequent, more prolonged, more generalised and more disabling. Persistent pain, swelling and deformity of joints is associated with accumulation of destructive and sometimes visible and palpable deposits of urate crystals under the skin (tophi). Less frequently crystals are deposited in, and damage the kidneys, or form stones in the urinary tract. Patients with asymptomatic hyperuricemia do not require treatment with urate lowering drugs, but efforts should be made to lower urate levels by encouraging gradual weight loss in overweight subjects and restricting the intake of red meat, seafood, alcohol (especially beer) and sugar sweetened soft drinks and colas.

How is gout diagnosed? In practice the diagnosis of gout is usually based on the distinctive features of an acute attack but the definitive diagnosis of gouty arthritis requires joint aspiration and demonstration of microscopic urate crystals in the joint fluid. The blood level of uric acid is not always raised at the time of an acute attack and may need to be repeated to clarify the diagnosis by demonstrating the hyperuricaemia when the flare has subsided.

How is gout treated?

Acute attacks are treated with either nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine,or corticosteroids often supplemented by analgesics and other measures such as elevation of the affected joint, application of ice or needling the inflamed joint to remove fluid (joint aspiration).

Lifestyle modification including: -
  • •gradual weight reduction in overweight patients
  • •reduction of intake of red meat and shellfish
  • •restriction of alcohol consumption (especially beer)
  • •limit consumption of sugar sweetened soft drinks
  • •avoidance of triggers such as binges of food and alcohol, crash diets, dehydration and local trauma.

Assessment and optimum treatment of any associated medical disorders eg:
  • •Obesity
  • •Hypertension
  • •Hyperlipidaemia
  • •Diabetes
  • •Chronic Kidney Disease
  • •Psoriasis
  • •Osteoarthritis
Urate lowering drugs. If flares of acute gout recur and hyperuricaemia persists despite lifestyle modification, urate-lowering drug therapy is required.

Uricostatic drugs which block the production of urate by inhibiting the enzyme xanthine oxidase are the drugs usually prescribed to lower and maintain serum levels of urate at or below a target level of 0.36 mmol/L (6mg/dL). This is below the concentration threshold above which urate crystals can form in the body.

• Allopurinol is most widely used and has been available for many years. It is usually started at low dose, after the acute attack of gout has settled, and the dose is then increased until the target serum urate has been achieved.

• Febuxostat has more recently become available in Europe as an alternative xanthine oxidase inhibitor for the treatment of hyperuricaemia in patients with gout. However, the National Institute for Clinical Health and Excellence (NICE) currently recommends that the use of febuxostat is restricted to use as a second- line option for the treatment of patients with gout in England and Wales who are intolerant of allopurinol or for whom allopurinol is contraindicated.

Uricosuric drugs such as sulfinpyrazone, probenecid and benzbromarone are much less frequently used urate lowering drugs. They work by increasing the elimination of urate through the kidneys rather than by blocking its production.

Gout flares. After commencing any urate lowering drug patients have a heightened risk of suffering acute gout flares until the blood uric acid level has been reduced to target for some time. In order to reduce the risk of such flares patients are frequently given a low dose of colchicine or an NSAID to take together with their urate lowering drug for up to 6 months.


The FAST STUDY

Allopurinol and febuxostat have each been shown to be safe and effective drugs for the treatment of gout.

The FAST study is designed to find out whether febuxostat is safer, less safe or just as safe as allopurinol for long term use in practice. This information will be of great value to everyone who needs to take these drugs on a regular basis. It will allow doctors to make the best choice for people with gout, not just for their joint pain and arthritis but also for any associated medical disorders they may have and for their general health.