Improving gout management one step at a time

Case scenario

Darrel, a 67-year-old male, presents to your pharmacy with his regular prescription for allopurinol 300 mg/day, which he has taken for more than 2 years.

Darrel has a history of gout but no tophi and is frustrated that he continues to experience gout flares despite taking the allopurinol regularly. To treat his frequent gout flares, he usually takes ibuprofen. You look at the Therapeutic Guidelines and note that the dose of allopurinol should be titrated until target urate levels are achieved. You ask Darrel, and he does not recall having his urate levels measured, at least not recently.

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Introduction

Gout is a type of inflammatory arthritis. It is a chronic condition, associated with consistently high serum urate concentrations (hyperuricaemia), with episodic occurrences of painful gout flares (attacks) in one or more joints, often the big toe.

Acute management involves reducing the pain and inflammation associated with the gout flare by taking medication, such as corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or colchicine. Treatment involves ongoing reduction of serum urate concentrations with urate-lowering therapy (ULT), such as allopurinol or febuxostat.

Pharmacists play a key role in supporting people with gout, including ensuring the optimal use of medicines. Pharmacist-led services have demonstrated effectiveness over current standard care in achieving target serum urate and adherence to ULT.^1–4

Epidemiology

Gout prevalence is increasing worldwide, including in Australia, where it is estimated to affect 4.8–6.8% of the total population (self-reported).⁵ Gout is almost four times more common in males than females and prevalence increases with age.^6–8

Gout has a 3-fold higher prevalence in Māori and Pacific Islander peoples compared to those of European descent.⁹ The burden of gout for Aboriginal and Torres Strait Islander peoples is increasing, although less well understood. The current prevalence (estimated at 6.7% in those 20 years or older) is likely underestimated due to underdiagnosis and low rates of self-reporting.⁵

Aetiology and pathophysiology

Gout is the deposition and accumulation of monosodium urate crystals in joints or surrounding tissues that can occur with increased serum urate concentrations. These crystals can trigger pain, inflammation and swelling.¹⁰ Untreated gout can lead to deposits of monosodium urate forming tophi, which can erode and destroy affected joints and limit movement.

Serum urate concentrations are elevated (greater than 0.42 mmol/L) in people with gout, generally due to either overproduction or reduced clearance. Uric acid is the final product in the metabolism of dietary and endogenous purines (occurs in the liver).¹⁰ It is eliminated by the kidneys (two-thirds) and the gut (one-third).¹¹

Risk factors for the development of gout include^8,10,12:

• a genetic predisposition (i.e. a family history)
• male sex (gout rarely occurs in females before menopause)
• older age
• comorbidities such as hypertension, dyslipidaemia, type 2 diabetes, obesity and chronic kidney disease
• a diet rich in purines (e.g. red meat, beer)
• concomitant medicines that reduce uric acid clearance via the kidneys (e.g. thiazide diuretics, loop diuretics, angiotensin-converting enzyme inhibitors, beta blockers
  and cyclosporin).
• Fluctuations in serum urate concentrations are thought to trigger a gout flare (e.g. when ULT is started).¹³

Any medicine, condition (e.g. sepsis, dehydration, surgery) or dietary change that causes a rapid increase or decrease in serum urate concentrations can precipitate or prolong a gout flare.¹³

Clinical features

Gout flares are characterised by sudden intense pain in a single joint, often the big toe, accompanied with redness, swelling and tenderness of the affected joint. The pain typically peaks after 12–24 hours, then slowly reduces irrespective of acute treatment. A gout flare can spontaneously resolve within a week. With treatment, symptoms abate in 3–5 days.¹⁴

Gout flares vary in frequency depending on hyperuricaemia severity. Their frequency, severity, duration and the number of joints affected may increase without treatment. Eventually, some people develop tophi, large masses of monosodium urate crystals that form in joints and soft tissues and appear as hard “white” lumps in the elbows (olecranon bursae), knees (prepatellar bursae) and peripheral joints (e.g. the toes and fingers). Chronic tophaceous gout is destructive and, unless treated, may cause significant disability.¹⁵

Diagnosis and differential diagnosis 

Diagnosis of gout requires the identification of monosodium urate crystals in the aspirated synovial fluid of the affected joint, under polarised microscopy.^14,15 If joint aspiration is not feasible, diagnosis can be made based on clinical assessment (e.g. medical history, physical exam, blood test and imaging of the affected joint).^13,14

Although all patients with suspected gout should have their serum urate concentration measured, hyperuricaemia in isolation does not confirm a diagnosis of gout.¹⁵ In fact, serum urate concentrations can be normal or lower during a gout flare, so additional monitoring is required at least 2 weeks after a gout flare has subsided.¹⁶

Differential diagnosis may include pseudogout, formally known as deposition disease, where the symptoms can mimic those of gout and other types of inflammatory arthritis. Pseudogout is caused by the accumulation of calcium pyrophosphate dihydrate crystals in cartilage and the synovial membrane of joints.¹⁷ Pseudogout typically affects larger joints rather than small joints such as the big toe, so pathology testing (e.g. joint aspirate) and potentially imaging are required for a differential diagnosis.¹⁷

Symptoms of infective arthritis can also be similar to those of gout. Clinical suspicion (e.g. recent history of penetrating trauma) and/or aspiration of synovial fluid for microscopy, culture and sensitivities (MCS) may be required to exclude infection.¹⁵

Treatments

Asymptomatic hyperuricaemia does not require ULT.¹⁷ Instead, it is recommended that modifiable risk factors are addressed, such as avoiding dietary triggers, maintaining ideal body weight and limiting the intake of alcohol.¹⁷

Although evidence for improved gout outcomes is lacking, it is generally thought that lifestyle modification can improve cardiometabolic risk factors and outcomes.¹⁷

Acute treatment of a gout flare aims to provide symptom relief. Chronic treatment aims to reduce serum urate concentrations to prevent future gout flares, joint destruction and disability, and resolve tophi. ULT is lifelong, with dose escalation based on a treat-to-target approach.¹⁸

Treatment of acute gout

Acute gout treatment is effective with NSAIDs, corticosteroids (oral or intra-articular injection) or low-dose colchicine.¹⁸

Drug choice is influenced by patient factors, including comorbidities, other medicines, joint involvement and preference. Local corticosteroid injection into the affected site, oral prednisolone (15–30 mg daily) or an oral NSAID until symptoms subside (typically 3–5 days) are recommended as first-line options.¹

Colchicine (1 mg initially followed by 500 microgram 1 hour later) is recommended as second-line therapy due to adverse effects.¹⁵ This recommended low-dose regimen is as effective and safer than higher-dose regimens and should not be repeated within 3 days. NSAIDs and colchicine are contraindicated in patients with severe kidney disease, and dose adjustment may be required for those with mild-moderate impairment.¹⁴

Guidelines recommend that ULT can be started and modified but not stopped during a gout flare.¹⁸

ULT initiation

ULT is recommended for all people with a confirmed clinical diagnosis of gout, especially those with tophaceous gout, radiographic joint damage and frequent gout flares.¹⁴

Recent guidance suggests that ULT can be commenced during a gout flare, provided that flare prophylaxis treatment is adequate.^19–21 Alternatively, it can be commenced 2–4 weeks after a flare has subsided.²² ULT is safe to start and modify slowly with flare prophylaxis during a gout flare, however should not be stopped to avoid sudden changes in serum urate concentrations that can prolong or worsen the attack.¹⁴

Titration of ULT should follow a treat-to-target approach, aiming for a serum urate concentration of <0.36 mmol/L for non-tophaceous gout or <0.30 mmol/L with tophi, chronic gouty arthritis and recurrent gout flares.¹⁵ Failure to adjust the dose of ULT to achieve the target level is a common reason for treatment failure.²³ Once the target serum urate concentration has been achieved, ULT should be continued long term to maintain the target level, and patient pathology should be reviewed at 6 months and then annually.¹⁴

First-line therapy is the xanthine oxidase inhibitor, allopurinol. Second-line options are febuxostat (xanthine oxidase inhibitor) or probenecid (uricosuric agent).¹⁵ Renal impairment is not a contraindication to allopurinol use.²³ Uricosuric agents (e.g. probenecid) can be added to allopurinol monotherapy if target serum urate levels can’t be achieved with allopurinol alone (e.g. if effective allopurinol dose is not tolerated).¹⁵

Allopurinol should be initiated at 50 mg daily for 4 weeks, then increased by 50 mg increments every 4 weeks (when eGFR <60 mL/min/1.73m²) or 100 mg increments every 4 weeks (when eGFR ≥60 mL/min/1.73m²) (maximum dose 900 mg daily) until attainment of target level.¹⁵

Flare prophylaxis during ULT initiation/up-titration

Due to the increased risk of gout flares associated with starting or modifying ULT, flare prophylaxis is recommended for all patients, with colchicine (500 micrograms once or twice daily) being the first-line choice.¹⁵ This should be reduced to 250 micrograms daily if CrCl <30 mL/min or in people who experience diarrhoea.

Low-dose NSAIDs or corticosteroids can be used if colchicine is contraindicated, not tolerated or ineffective.¹⁵ The typical duration for flare prophylaxis is at least 6 months.

Colchicine should be continued until target serum urate concentration is reached and the patient has no further gout flares.¹⁴ Prophylaxis may be extended in some individuals such as those that have gout with tophi.¹⁴

Obstacles with ULT

The main issues with ULT are poor adherence, early cessation, under-prescribing, inadequate prescribing of flare prophylaxis (e.g. colchicine) at initiation, and failure to titrate doses to achieve target serum urate concentration.^24–26

Adherence to ULT is poor in Australia, with 34% of patients discontinuing allopurinol in the first month.²⁷ It is known that patients will not prioritise their gout management over their other conditions, unless they are experiencing a gout flare.²⁸ The stigma surrounding gout means patients may be reluctant to seek care.²⁹ In general, there is a reluctance from patients to initiate and/or continue ULT due to misconceptions that it is unnecessary if no longer experiencing gout flares, or ineffective if the gout flares occur despite therapy.²⁸ Educating the patient around the nature of the disease and the role of therapy in its management, as well as suggesting the use of reminder systems and family/peer support, can help improve adherence to ULT.

Non-pharmacological management

Pharmacists can help patients understand some of the non-pharmacological management options available by explaining the predisposing factors that may put a patient at increased risk of developing gout. Non-pharmacological management options include³⁰:

• maintaining a healthy balanced diet
• adequate hydration to reduce the concentration of uric acid in the blood
• maintaining a healthy weight through diet and exercise
• limiting alcoholic beverages
• being aware of potential triggers.

Follow-up

Once ULT has been initiated, ongoing monitoring should include serum urate concentration, renal function, liver biochemistry (with febuxostat), full blood count (with probenecid), as well as the frequency of gout flares.¹⁴ Serum uric acid should be measured monthly during the dose titration phase, then at 6 months and then annually thereafter.³¹

Practitioners should regularly (e.g. at 6-monthly intervals) monitor disease progression, particularly if a patient decides not to embark on ULT. Patients should be advised to return for earlier review if they have another gout flare.¹⁴

Consumer support and resources are available through Arthritis Australia and the Australian Rheumatology Association. These include a Gout and Diet fact sheet that provides consumers with information on self-management lifestyle strategies like weight loss, reducing alcohol intake and following a healthy, balanced diet. There are available resources that have been specifically designed for Aboriginal and Torres Strait Islander peoples living with gout. These resources provide valuable support for a condition that faces stigma and challenges with therapy adherence.

Several consumer resources have been developed by Arthritis New Zealand and Health Navigator Charitable Trust to cater for Māori and Pacific Islander peoples.

Knowledge to practice

Pharmacists are key when it comes to quality use of gout medicines to reduce gout flares and prevent complications. This includes supporting the initiation of ULT using a treat-to-target approach, use of flare prophylaxis when initiating or changing the dose of ULT, regular monitoring of serum urate levels, encouraging adherence, empowering consumers to engage with their gout care, and dispelling myths, misconceptions and stigma. International multidisciplinary models of practice are often pharmacist-led, highlighting the potential for Australian pharmacists in this space.

Pharmacists should support patients in achieving target serum urate concentrations to reduce the frequency and severity of gout flares. They should also improve consumer awareness and understanding of gout as a chronic condition that requires long-term management to realise treatment benefits. Increased consumer awareness of gout causes and prevention, and treatment options will encourage patients to seek medical care. Pharmacists are well placed to help the patient understand the role of their medicines and ensure the patient understands the expected outcomes, including the possibility of experiencing a flare during treatment initiation and the importance of persisting with treatment.

Conclusion

Gout is a chronic arthritis associated with significant pain, joint damage and reduced quality of life. Gout is often poorly managed, with low rates of allopurinol prescribing, serum uric acid monitoring, achievement of urate targets and adherence to therapy. However, it can be effectively treated and its complications prevented with adherence to lifelong ULT using a treat-to-target approach. Pharmacists can help support patients and other healthcare professionals to ensure quality use of gout medications.

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Key points

• Gout can be effectively treated, and its complications prevented, with adherence to lifelong ULT using a treat-to-target approach.
• Ensure patients have a clear understanding of treatment expectations. Effective gout treatment can be hindered by misconceptions of false treatment failure, or discontinuation of ULT after a flare due to perceived resolution.
• Quality use of gout medicines requires regular monitoring of serum urate concentration and use of flare prophylaxis when initiating or changing the dose of ULT.
• Pharmacists play a key educational role for prescribers and patients. This includes improving knowledge on its causes and management while addressing misconceptions and stigma.

References

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Our author

Dr Sophie Stocker (she/her) BSc (Hon I), PhD is a Senior Lecturer at the School of Pharmacy, University of Sydney. Her research focuses on understanding variability in response to medicines and how this can be managed to optimise patient care.

Our reviewer

Hana Numan (she/her) BPharm (NZ), PGDipClinPharm (NZ), MPS (NZ)