What are the guidelines for managing gouty flares?

Management of Acute Gouty Flares

For acute gout flares, immediately initiate treatment with colchicine, NSAIDs, or oral corticosteroids—these three agents are equally effective first-line options, and early initiation is far more important than which specific agent you choose. 1

Acute Flare Treatment Algorithm

First-Line Agents (Choose Based on Patient Factors)

Colchicine:

• Most effective when started within 12 hours of symptom onset 1
• Dosing: 1.2 mg (two 0.6 mg tablets) at first sign of flare, followed by 0.6 mg one hour later (maximum 1.8 mg over one hour) 1
• Low-dose regimen is strongly preferred over high-dose due to similar efficacy with fewer adverse effects 1
• Critical contraindications: Avoid in severe renal impairment (CrCl <30 mL/min) or patients on strong CYP3A4/P-glycoprotein inhibitors (clarithromycin, ritonavir, ketoconazole) due to risk of fatal toxicity 1, 2
• For dialysis patients: single 0.6 mg dose only, not to be repeated more than once every two weeks 2

NSAIDs:

• Use full FDA-approved anti-inflammatory doses (e.g., naproxen 500 mg twice daily, indomethacin 50 mg three times daily) 1
• Absolute contraindications: peptic ulcer disease, renal failure (CrCl <30 mL/min), uncontrolled hypertension, heart failure 1, 3
• Particularly dangerous in elderly patients with renal impairment—avoid in this population 3

Oral Corticosteroids:

• Prednisone 30-35 mg daily for 3-5 days 1
• Preferred agent for patients with: renal impairment, cardiovascular disease, gastrointestinal contraindications to NSAIDs, uncontrolled hypertension, or heart failure 1
• Safer than NSAIDs in patients with multiple comorbidities 1

Special Situations

Monoarticular or Oligoarticular Flares (1-2 large joints):

• Intra-articular corticosteroid injection is highly effective and preferred over systemic therapy 1

Patients Unable to Take Oral Medications:

• Parenteral glucocorticoids are strongly recommended over IL-1 inhibitors or ACTH 1

Contraindications to All First-Line Agents:

• IL-1 inhibitors (canakinumab 150 mg subcutaneously) are conditionally recommended for patients with frequent flares who cannot tolerate colchicine, NSAIDs, or corticosteroids 1
• Absolute contraindication to IL-1 blockers: current active infection 1

Adjunctive Measures

• Topical ice application is conditionally recommended as adjuvant therapy 1
• Rest the affected joint 4

Urate-Lowering Therapy During Acute Flares

Continue existing urate-lowering therapy (ULT) during the acute flare—do not stop it. 1 Interrupting ULT worsens the flare and complicates long-term management 1.

Starting ULT during an acute flare:

• The American College of Rheumatology conditionally recommends starting ULT during the flare rather than waiting for resolution, provided you initiate concomitant anti-inflammatory prophylaxis 5, 1

Prophylaxis When Initiating Urate-Lowering Therapy

When starting any ULT, strongly recommend concomitant anti-inflammatory prophylaxis to prevent treatment-induced flares. 5, 1

Prophylaxis regimen:

• First-line: Low-dose colchicine 0.5-0.6 mg once or twice daily 1, 6
• Alternatives: Low-dose NSAIDs (naproxen 250 mg twice daily) or low-dose corticosteroids (prednisone/prednisolone) 5, 6
• Duration: Continue for 3-6 months (strongly recommended over <3 months), with ongoing evaluation and continued prophylaxis if flares persist 5

Indications for Urate-Lowering Therapy

Strong recommendations to initiate ULT:

• ≥1 subcutaneous tophi 5
• Radiographic damage attributable to gout (any modality) 5
• Frequent gout flares (≥2 per year) 5

Conditional recommendations:

• Patients with >1 prior flare but infrequent flares (<2/year) 5
• First flare with CKD stage ≥3, serum urate >9 mg/dL, or urolithiasis 5

Conditional recommendation AGAINST ULT:

• First flare without the above risk factors 5
• Asymptomatic hyperuricemia (no prior flares or tophi)—24 patients would need treatment for 3 years to prevent one incident flare 5

ULT Selection and Dosing

Allopurinol is strongly recommended as the preferred first-line agent for all patients, including those with CKD stage ≥3. 5

Starting doses (to minimize hypersensitivity risk):

• Allopurinol: ≤100 mg/day (lower in CKD), titrate to target serum urate <6 mg/dL 5
• Febuxostat: ≤40 mg/day, titrate as needed 5
• Probenecid: 500 mg once or twice daily, titrate upward 5

Treat-to-target strategy:

• Strongly recommend dose titration guided by serial serum urate measurements to achieve and maintain serum urate <6 mg/dL 5
• Continue ULT indefinitely once target achieved 5

Critical Pitfalls to Avoid

• Delaying treatment initiation: Early intervention is the single most important determinant of success, not which agent is chosen 1, 4
• Using colchicine in severe renal impairment or with strong CYP3A4 inhibitors: Can result in fatal toxicity 1, 2
• Prescribing NSAIDs in elderly patients with renal impairment, heart failure, or peptic ulcer disease: High risk of serious adverse events 1, 3
• Stopping ULT during acute flare: Worsens the flare and complicates long-term management 1
• Starting ULT without prophylaxis: Increases risk of treatment-induced flares and poor adherence 5, 1
• Using high-dose allopurinol initially: Start low (≤100 mg/day) to minimize hypersensitivity reactions, especially in elderly or those with renal impairment 5, 3