What is important when starting urate-lowering therapy (ULT) for hyperuricemia?

From the Guidelines

When starting urate-lowering therapy (ULT) for hyperuricemia, it is crucial to initiate treatment with allopurinol as the preferred first-line agent, starting at a low dose with subsequent dose titration, and concomitant anti-inflammatory prophylaxis therapy to prevent gout flares. According to the 2020 American College of Rheumatology guideline for the management of gout 1, allopurinol is recommended over all other ULT as the preferred first-line agent for all patients, including those with CKD stage >3. The guideline also recommends starting allopurinol at a low dose (≤100 mg/day) and gradually increasing the dose every 2-4 weeks until reaching the target serum uric acid level below 6 mg/dL (or below 5 mg/dL for severe gout) 1.

Some key points to consider when starting ULT include:

• Initiating concomitant anti-inflammatory prophylaxis therapy, such as colchicine, NSAIDs, or prednisone/prednisolone, for a duration of at least 3-6 months to prevent gout flares 1
• Starting with a low dose of allopurinol (50-100 mg daily) or febuxostat (20-40 mg daily) and gradually increasing the dose as needed 1
• Regular monitoring of serum uric acid levels to guide dose adjustments 1
• Considering HLA-B*5801 testing in high-risk populations (Korean, Han Chinese, Thai) before starting allopurinol therapy to prevent severe hypersensitivity reactions
• Ensuring patients understand that urate lowering therapy is typically lifelong and that temporary increases in gout attacks may occur when starting treatment despite prophylaxis
• Addressing modifiable risk factors like alcohol consumption, high-purine diet, and certain medications to reduce the risk of gout flares 1

It is essential to prioritize patient education and medication adherence, as discontinuation of ULT can lead to recurrent gout attacks. By following these guidelines and recommendations, healthcare providers can effectively manage hyperuricemia and improve patient outcomes.

From the FDA Drug Label

The upper limit of normal is about 7 mg/dL for men and postmenopausal women and 6 mg/dL for premenopausal women. 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 In transferring a patient from a uricosuric agent to allopurinol tablets, the dose of the uricosuric agent should be gradually reduced over a period of several weeks and the dose of allopurinol tablets gradually increased to the required dose needed to maintain a normal serum uric acid level. A fluid intake sufficient to yield a daily urinary output of at least 2 liters and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable.

When starting urate-lowering therapy (ULT) for hyperuricemia, it is important to:

• Continue therapy with colchicine and/or anti-inflammatory agents until serum uric acid has been normalized and there has been freedom from acute gouty attacks for several months.
• Gradually reduce the dose of uricosuric agents and increase the dose of allopurinol when transferring a patient from a uricosuric agent to allopurinol.
• Ensure a fluid intake sufficient to yield a daily urinary output of at least 2 liters and maintain a neutral or slightly alkaline urine.
• Monitor serum uric acid levels to determine the correct size and frequency of dosage 2.

From the Research

Important Considerations for Urate-Lowering Therapy (ULT)

When starting urate-lowering therapy (ULT) for hyperuricemia, several factors are important to consider:

• The choice of ULT agent, such as allopurinol or febuxostat, and the appropriate dosing regimen 3, 4
• The need for concomitant flare prophylaxis, as only 43.1% of patients received this in one study 4
• The potential for adverse effects, such as liver function abnormalities, rash, nausea, and arthralgias 3, 4
• The importance of achieving target serum uric acid (sUA) levels, which can help reduce gout flares and improve symptoms 3, 4, 5
• The consideration of combination therapy with a uricosuric and a xanthine oxidase inhibitor (XOI) for patients who do not meet treatment targets with XOI monotherapy alone 6

Patient Factors to Consider

Patient factors that can influence the success of ULT include:

• Renal function, as dosage adjustments may be necessary for patients with renal insufficiency 3
• Tolerance to ULT agents, as some patients may experience adverse effects or be unable to achieve target sUA levels 3, 7
• Presence of tophi or other comorbidities, which can affect treatment outcomes and persistence with ULT 7
• Health literacy, as poor health literacy was a common reason for ULT discontinuation in one study 7

Treatment Outcomes

Studies have shown that ULT can improve treatment outcomes, including:

• Reductions in sUA levels and gout flares 3, 4, 5
• Improvements in endothelial function and reductions in systemic inflammation 5
• Increased persistence with treatment, particularly with febuxostat compared to allopurinol 7