Principles of pharmacological management for chronic gout

Graf, 2015 Kiltz, 2017 Kydd, Seth, Buchbinder, Edwards, 2014 Kydd, Seth, Buchbinder, Falzon, 2014

Urate-lowering therapy aims to achieve a serum uric acid concentration that:

dissolves existing monosodium urate crystals in the joints, soft tissues, and kidneys; and prevents the formation of new crystals
reduces the frequency and severity of acute attacks, eventually leading to the absence of acute attacks
resolves tophi.

Lifelong urate-lowering therapy is recommended for all patients with a confirmed diagnosis of gout, and can be safely started alongside treatment for an acute gout attack Taylor, 2012. Starting or increasing urate-lowering therapy is associated with a high risk of gout flare, so flare prophylaxis is also recommended.

A conversation introducing urate-lowering therapy should be started with all patients with confirmed gout. The importance of starting therapy is much higher in patients with one or more of the following:

one or more subcutaneous tophi
evidence of radiographic damage
two or more flares annually
patients who have experienced more than one flare after a first gout attack and have a high serum urate with concomitant moderate to severe kidney impairment or kidney stones.

Note: Lifelong urate-lowering therapy is recommended for all patients with a confirmed diagnosis of gout, and is safe to start when treating someone with acute gout.

Following a first acute attack of gout, patients may be reluctant to start lifelong urate-lowering therapy. Having a discussion about gout and the nature of the disease is pivotal to the patient making an informed choice to start urate-lowering therapy. If patients decide not to start urate-lowering therapy, arrange regular follow-up appointments (eg at 6-monthly intervals) to monitor disease progression. Advise patients to return for review earlier if they have another acute attack of gout.

Urate-lowering therapy is titrated using a treat-to-target approach. It is important that target serum uric acid concentrations are achieved and maintained because patients will otherwise accrue all the harms of drug therapy with none of the benefits.

Note: Titrate urate-lowering therapy using a treat-to-target approach.

Table 1. Target serum uric acid concentrations
Patient group	Target concentration [NB1]
People with tophi, chronic arthropathy or frequent attacks	Less than 0.30 mmol/L (5 mg/dL) initially until total crystal dissolution and resolution of gout, then less than 0.36mmol/L (6 mg/dL)
People with nontophaceous gout	Less than 0.36mmol/L (6 mg/dL)
Note: NB1: Measure serum uric acid concentration monthly during the dose titration phase. Once the patient has achieved the target serum uric acid concentration, repeat measurements at 6 months, and then annually.

Failure to adjust the dose of urate-lowering therapy to achieve the target serum uric acid concentration is a common reason for treatment failure. Once the target serum uric acid concentration has been achieved, urate-lowering therapy should be continued to maintain the target concentration of less than 0.36mmol/L (6 mg/dL). Lower levels of serum uric acid are not recommended over the longer term because uric acid might protect against some neurodegenerative diseases.