Can urate-lowering therapy (ULT) and medications like colchicine (Colchicine) or nonsteroidal anti-inflammatory drugs (NSAIDs) be initiated during acute gout flare-ups?

Management of Medications During Acute Gout Flares

Yes, both anti-inflammatory medications (colchicine, NSAIDs, corticosteroids) and urate-lowering therapy can be initiated during acute gout flares, with anti-inflammatory agents being essential for flare treatment and ULT initiation being conditionally recommended during the flare rather than waiting for resolution. 1

Treatment of Acute Flares

First-Line Anti-Inflammatory Options

Acute gout flares should be treated as early as possible, and patients should be educated to self-medicate at the first warning symptoms. 1

The following are recommended first-line options for treating acute flares:

• Colchicine: Loading dose of 1.2 mg at first sign of flare, followed by 0.6 mg one hour later (maximum 1.8 mg over one hour period) 1, 2

  • Must be initiated within 12 hours of flare onset for optimal efficacy 1
  • Higher doses have not been found more effective 2

• NSAIDs: Full anti-inflammatory doses with proton pump inhibitors if appropriate 1

  • Avoid in patients with severe renal impairment 1

• Oral corticosteroids: 30-35 mg/day prednisolone equivalent for 3-5 days 1

  • Alternative dosing: 0.5 mg/kg/day for 5-10 days at full dose then stop, or 2-5 days at full dose followed by 7-10 day taper 3

• Intra-articular corticosteroid injection: After joint aspiration, particularly useful for 1-2 affected joints 1, 3

Combination Therapy for Severe Polyarticular Attacks

For severe polyarticular attacks involving multiple large joints, initial combination therapy is appropriate: 3

• Colchicine plus NSAIDs 3
• Oral corticosteroids plus colchicine 3
• Intra-articular steroids with any other modality 3

Critical Contraindications

Avoid colchicine in patients receiving strong P-glycoprotein and/or CYP3A4 inhibitors (cyclosporin, clarithromycin, ritonavir, ketoconazole, itraconazole) due to risk of fatal colchicine toxicity. 1, 2

Initiating Urate-Lowering Therapy During Acute Flares

Timing Recommendation

When ULT is indicated while a patient is experiencing a gout flare, starting ULT during the flare is conditionally recommended over waiting until the flare resolves. 1

This recommendation is based on:

• Time efficiency: Initiating therapy during the concurrent flare visit prevents risk of patient non-return 1
• Patient motivation: Patients experiencing acute symptoms are highly motivated to start long-term treatment 1
• Evidence of safety: Two small RCTs and one observational study demonstrate that starting ULT during a flare does not significantly extend flare duration or severity 1, 4

Starting Doses for ULT

All ULT must be started at low doses regardless of whether initiated during or after a flare: 1

• Allopurinol: ≤100 mg/day (lower in CKD stage ≥3), increase by 100 mg increments every 2-4 weeks 1
• Febuxostat: ≤40 mg/day with subsequent titration 1
• Probenecid: 500 mg once or twice daily with dose titration 1

Mandatory Anti-Inflammatory Prophylaxis with ULT

Strong Recommendation for Prophylaxis

Concomitant anti-inflammatory prophylaxis therapy (colchicine, NSAIDs, or prednisone/prednisolone) is strongly recommended when initiating ULT, regardless of whether started during or after a flare. 1

This recommendation is supported by 8 RCTs and 2 observational studies showing moderate certainty of evidence. 1

Duration of Prophylaxis

Prophylaxis must be continued for 3-6 months (preferably 6 months) rather than <3 months, with ongoing evaluation and continued prophylaxis as needed if flares persist. 1

Evidence shows:

• Flare rates increase sharply (up to 40%) at the end of 8 weeks of prophylaxis 5
• Flare rates remain consistently low (3-5%) with 6 months of prophylaxis 5
• Shorter durations are associated with flares upon cessation 1

Prophylaxis Regimens

First-line prophylaxis options: 1, 3

• Colchicine: 0.5-1 mg/day (0.6 mg once or twice daily), adjusted for renal function 1, 3
• Low-dose NSAIDs: If colchicine contraindicated or not tolerated 1
• Low-dose prednisone: <10 mg/day if colchicine and NSAIDs contraindicated 3

Critical Prophylaxis Considerations

In patients with renal impairment or statin treatment, monitor for potential neurotoxicity and/or muscular toxicity with prophylactic colchicine. 1

If already on prophylactic colchicine when a flare occurs, colchicine can be used for flare treatment at doses not to exceed 1.2 mg followed by 0.6 mg one hour later, then wait 12 hours before resuming prophylactic dosing. 2

Continuing ULT During Acute Flares

If a patient is already on ULT when an acute flare occurs, continue the ongoing ULT without interruption during the acute attack. 3

This prevents further urate mobilization and maintains progress toward target serum urate levels.

Common Pitfalls to Avoid

• Do not delay ULT initiation indefinitely waiting for "perfect" timing—the conditional recommendation supports starting during flares when ULT is indicated 1
• Do not start ULT without anti-inflammatory prophylaxis—this is a strong recommendation with moderate evidence 1
• Do not stop prophylaxis prematurely at 8 weeks—continue for at least 3-6 months 1, 5
• Do not start ULT at high doses—always begin low and titrate to avoid precipitating additional flares 1
• Do not use colchicine with strong CYP3A4/P-gp inhibitors—risk of fatal toxicity 1, 2