Should allopurinol be initiated during or after an acute gout flare?

From the Guidelines

Allopurinol can be started during an acute gout flare, as conditionally recommended by the 2020 American College of Rheumatology guideline for the management of gout 1. When initiating allopurinol, it is essential to start with a low dose (typically ≤100 mg/day, and lower in patients with chronic kidney disease) and gradually increase by 100 mg increments every 2-4 weeks until reaching the target dose (often 300-600 mg daily) or until the serum urate level is below 6 mg/dL. Some key points to consider when starting allopurinol include:

• Using a low starting dose to minimize the risk of adverse effects and gout flares
• Gradually increasing the dose to achieve the target serum urate level
• Providing concomitant anti-inflammatory prophylaxis therapy for a duration of at least 3–6 months to prevent flares during allopurinol initiation
• Monitoring serum urate levels regularly to guide dose titration and ensure the target level is achieved. Allopurinol works by inhibiting xanthine oxidase, the enzyme responsible for uric acid production, thereby reducing serum urate levels and allowing existing crystal deposits to dissolve over time. It is crucial to note that the decision to start allopurinol during an acute gout flare should be made on a case-by-case basis, taking into account the individual patient's needs and medical history. The American College of Rheumatology guideline provides a framework for managing gout, but it is essential to consider the latest evidence and clinical judgment when making treatment decisions 1.

From the FDA Drug Label

To reduce the possibility of flare-up of acute gouty attacks, it is recommended that the patient start with a low dose of allopurinol tablets (100 mg daily) and increase at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained but without exceeding the maximal recommended dosage. While adjusting the dosage of allopurinol tablets in patients who are being treated with colchicine and/or anti-inflammatory agents, it is wise to continue the latter therapy until serum uric acid has been normalized and there has been freedom from acute gouty attacks for several months

Allopurinol initiation should be done with caution in patients with acute gout flare. The recommended approach is to start with a low dose of 100 mg daily and gradually increase it to minimize the risk of flare-up. It is also recommended to continue anti-inflammatory agents or colchicine until serum uric acid levels are normalized and there have been no acute gouty attacks for several months 2.

From the Research

Allopurinol Initiation in Acute Gout Flare

• The optimal timing of allopurinol initiation in acute gout flare is a topic of debate, with conflicting guidelines available 3.
• A randomized controlled trial compared early and late allopurinol initiation in acute gout flare, finding no significant difference in time to complete resolution of arthritis between the two groups 4.
• The study suggests that early allopurinol initiation during an acute gout flare does not lead to significant changes in time to resolution, flare recurrence, and inflammatory markers 4.

Predictors of Gout Flares

• A post hoc analysis of a 12-month double-blind placebo-controlled noninferiority trial identified predictors of gout flares in patients starting allopurinol using the "start-low go-slow" dose escalation strategy 5.
• The analysis revealed that a gout flare in the month before starting allopurinol and a starting dose of 100 mg allopurinol were significant predictors of gout flares in the first six months 5.
• Other predictors of gout flares in the last six months of the trial included receipt of colchicine, at least one flare in the month before stopping study drug, and serum urate ≥0.36 mmol/L at month 6 5.

Clinical Characteristics and Health Care Utilization

• A population-based cohort study described the clinical characteristics and health care utilization patterns in patients with gout who were newly prescribed allopurinol, febuxostat, or colchicine 6.
• The study found that patients who started allopurinol, febuxostat, or colchicine for gout generally had hyperuricemia and multiple comorbidities, with febuxostat initiators having more comorbidities and greater use of health care resources and gout-related drugs than the other groups 6.
• The doses of allopurinol and febuxostat were rarely increased during follow-up, with median daily doses at both the start and end of treatment being 300 mg for allopurinol and 40 mg for febuxostat 6.