What is the recommended management of an acute gout flare in an adult, including first‑line NSAIDs and alternatives such as colchicine, corticosteroids, or IL‑1 inhibitors when contraindications like chronic kidney disease (eGFR < 30 mL/min), peptic ulcer disease, heart failure, or anticoagulation are present?

Management of Acute Gout Flare

First-Line Treatment Selection

For most patients with an acute gout flare, choose between NSAIDs, colchicine, or corticosteroids based on renal function, gastrointestinal risk, and cardiovascular comorbidities—all three are equally effective first-line options. 1, 2

Treatment Algorithm Based on Comorbidities

When eGFR < 30 mL/min, chronic kidney disease stage 4-5:

• Oral corticosteroids are the safest first-line choice: prednisone 30-35 mg once daily for 5 days (no taper needed for most patients). 1, 3, 2
• Avoid NSAIDs entirely—they precipitate acute kidney injury in severe renal impairment. 1, 3
• Avoid colchicine in severe renal impairment (eGFR <30 mL/min) due to fatal neurotoxicity and myotoxicity risk. 1, 3
• No dose adjustment required for corticosteroids in renal failure. 3

When peptic ulcer disease or recent GI bleeding is present:

• Oral corticosteroids are preferred: prednisone 30-35 mg daily for 5 days. 3, 2
• NSAIDs are absolutely contraindicated with active or recent GI bleeding. 1
• If NSAIDs must be used, combine with proton pump inhibitor, though corticosteroids remain safer. 1

When heart failure or significant cardiovascular disease is present:

• Oral corticosteroids are preferred: prednisone 30-35 mg daily for 5 days. 3, 2
• NSAIDs worsen heart failure and increase cardiovascular event risk. 1, 4
• Colchicine is safe in cardiovascular disease and may reduce myocardial infarction risk. 4

When on anticoagulation therapy:

• Oral corticosteroids are the safest choice: prednisone 30-35 mg daily for 5 days. 1, 3
• NSAIDs significantly increase bleeding risk when combined with anticoagulants. 1

Specific Dosing Regimens for First-Line Agents

Colchicine (when no contraindications present)

• Administer 1.2 mg (or 1 mg) at first sign of flare, followed by 0.6 mg (or 0.5 mg) one hour later, then 0.6 mg once or twice daily until attack resolves. 1
• Must start within 36 hours of symptom onset—effectiveness drops dramatically beyond this window. 1
• Most effective when given within 12 hours of symptom onset. 1
• This low-dose regimen (1.8 mg total in first hour) is as effective as high-dose colchicine (4.8 mg) but with significantly fewer gastrointestinal side effects (NNT = 5 for 50% pain reduction). 1

Critical colchicine contraindications:

• Absolute contraindication: concurrent strong CYP3A4 inhibitors (clarithromycin, erythromycin, ketoconazole) or P-glycoprotein inhibitors (cyclosporine, ritonavir)—fatal toxicity can occur. 1
• Severe renal impairment (eGFR <30 mL/min). 1
• Combined hepatic and renal impairment. 1

NSAIDs (when renal function normal, no GI/CV contraindications)

• Use full FDA-approved doses until complete attack resolution: naproxen, indomethacin, or sulindac are FDA-approved options. 1
• No single NSAID is more effective than others for gout. 5, 1
• Start within 24 hours of symptom onset and continue at full dose throughout the attack—do not reduce dose early. 1

NSAID contraindications:

• Severe renal impairment (eGFR <30 mL/min). 1
• Active or recent GI bleeding. 1
• Heart failure or significant cardiovascular disease. 1, 4
• Cirrhosis or hepatic impairment. 1
• Concurrent anticoagulation. 1

Oral Corticosteroids (preferred when NSAIDs/colchicine contraindicated)

• Prednisone 30-35 mg once daily for 5 days (fixed dose, no taper) is the simplest and most practical regimen for most patients. 3, 2
• Alternative regimen for severe attacks or higher rebound risk: prednisone 0.5 mg/kg/day for 2-5 days at full dose, then taper over 7-10 days. 3, 2
• Corticosteroids are as effective as NSAIDs with fewer adverse effects. 3, 2
• Level A evidence supports corticosteroids as equally effective as colchicine and NSAIDs. 3

Corticosteroid advantages:

• Safer and lower cost than IL-1 inhibitors. 3
• No dose adjustment needed for renal impairment. 3
• Fewer gastrointestinal adverse effects than NSAIDs. 3

Corticosteroid contraindications:

• Systemic fungal infections (absolute contraindication). 3, 2
• Active uncontrolled infection. 3

Short-term corticosteroid adverse effects to monitor:

• Elevated blood glucose (monitor closely in diabetes). 3, 2
• Fluid retention. 3, 2
• Dysphoria and mood disorders. 3, 2

Intra-articular Corticosteroid Injection

• For monoarticular or oligoarticular gout involving 1-2 large accessible joints, intra-articular corticosteroid injection is an excellent first-line option. 1, 2
• Provides targeted anti-inflammatory action with minimal systemic exposure. 3, 2
• Dose varies by joint size. 1

Intramuscular Corticosteroids (when oral route not feasible)

• Triamcinolone acetonide 60 mg IM is the specifically recommended dose for acute gout when patients cannot take oral medications. 3
• Alternative: methylprednisolone 40-140 mg IM (0.5-2.0 mg/kg). 3
• Indicated when NPO due to surgical/medical conditions, severe vomiting, or inability to tolerate oral therapy. 3

Intravenous Corticosteroids (when parenteral route required)

• Methylprednisolone 0.5-2.0 mg/kg IV (approximately 40-140 mg for most adults) when oral access not feasible. 3
• Repeat doses as clinically indicated. 3

Combination Therapy for Severe Polyarticular Attacks

For severe acute gout involving multiple large joints or polyarticular arthritis, initial combination therapy is more effective than monotherapy. 1, 2

Acceptable combination regimens:

• Colchicine + NSAIDs (provides synergistic anti-inflammatory effects targeting different pathways). 1, 2
• Oral corticosteroids + colchicine. 1, 2
• Intra-articular steroids + any other oral anti-inflammatory modality. 1, 2

Avoid this combination:

• Never combine NSAIDs with systemic corticosteroids—synergistic gastrointestinal toxicity occurs. 1

IL-1 Inhibitors (Reserved for Refractory Cases)

IL-1 inhibitors (canakinumab 150 mg subcutaneously or rilonacept) are reserved for patients with frequent flares who have contraindications to, or failure of, colchicine, NSAIDs, and corticosteroids. 1, 2

• Current infection is an absolute contraindication to IL-1 blockers. 2
• High cost and risk of serious infection limit use. 4
• At least 12 weeks required between canakinumab doses. 2

Monitoring Treatment Response

Define inadequate response as either <20% improvement in pain within 24 hours OR <50% improvement at ≥24 hours after initiating therapy. 1, 3

• If inadequate response occurs, consider alternative diagnosis or switch to another monotherapy or add a second agent. 3
• Continue treatment at full dose until the gouty attack has completely resolved—do not reduce dose early. 1

Critical Timing Considerations

• Treat acute gout flares as early as possible—effectiveness drops significantly when treatment is delayed beyond 12-36 hours. 1, 2
• The "pill in the pocket" approach allows fully informed patients to self-medicate at the first warning symptoms. 1, 2

Management During Urate-Lowering Therapy

• Continue urate-lowering therapy during acute flares with appropriate anti-inflammatory coverage—stopping does not shorten flare duration. 3, 2
• When initiating urate-lowering therapy, provide anti-inflammatory prophylaxis for at least 6 months (or 3 months after achieving target serum urate if no tophi present). 1

Prophylaxis options when starting urate-lowering therapy:

• First-line: low-dose colchicine 0.6 mg once or twice daily. 1
• First-line alternative: low-dose NSAID with proton pump inhibitor where indicated. 1
• Second-line: low-dose prednisone (<10 mg/day) if colchicine and NSAIDs contraindicated. 1, 3, 2
• Never use high-dose prednisone (>10 mg/day) for prophylaxis—inappropriate in most scenarios. 3, 2

Common Pitfalls to Avoid

• Delaying treatment beyond 12-36 hours significantly reduces effectiveness. 1
• Using high-dose colchicine (>1.8 mg in first hour)—provides no additional benefit but substantially increases gastrointestinal toxicity. 1
• Combining NSAIDs with systemic corticosteroids—causes synergistic GI toxicity. 1
• Using NSAIDs in severe renal impairment, heart failure, or with anticoagulation. 1, 4
• Using colchicine with strong CYP3A4/P-glycoprotein inhibitors or in severe renal impairment—fatal toxicity can occur. 1
• Stopping urate-lowering therapy during acute flares. 3
• Using high-dose corticosteroids (>10 mg/day) for prolonged prophylaxis. 3, 2