What is the most effective treatment option for a patient with acute gout and no contraindications, comparing naproxen (Nonsteroidal Anti-Inflammatory Drug (NSAID)), etoricoxib (NSAID), aceclofenac (NSAID), indomethacin (NSAID), and prednisone (corticosteroid)?

Treatment Selection for Acute Gout

For a patient with acute gout and no contraindications, initiate full-dose naproxen 500 mg twice daily or etoricoxib 120 mg once daily within 24 hours of symptom onset, as these are FDA-approved NSAIDs with equivalent efficacy and superior tolerability compared to indomethacin, while prednisone 30-35 mg daily represents an equally effective alternative with fewer gastrointestinal adverse events. 1, 2, 3

First-Line Treatment Algorithm

NSAIDs as Primary Choice

• Naproxen 500 mg twice daily is FDA-approved specifically for acute gout and should be continued at full dose until complete symptom resolution 1, 4
• Etoricoxib 120 mg once daily demonstrates equivalent efficacy to naproxen and indomethacin for pain reduction, with comparable safety to prednisolone 3
• Avoid indomethacin as a preferential choice—despite FDA approval, it causes more adverse effects without efficacy advantage over other NSAIDs 2, 5
• Aceclofenac is not FDA-approved for acute gout and lacks specific guideline recommendations for this indication 1, 2

Corticosteroids as Equally Effective Alternative

• Prednisone 30-35 mg daily (or 0.5 mg/kg/day) for 5 days without taper, or 2-5 days at full dose followed by 7-10 day taper, is equally effective as NSAIDs with fewer gastrointestinal adverse events 1, 2, 6, 3
• Six randomized controlled trials demonstrate no difference in time to symptom resolution or pain reduction between NSAIDs and corticosteroids 1
• Prednisolone may be more effective than indomethacin in reducing joint swelling specifically 3

Comparative Efficacy Data

Pain Relief

• All three agents (naproxen, etoricoxib, prednisone) produce similar pain reduction over 4 days of treatment 3
• NSAIDs demonstrate 50% pain reduction at 24 hours in 73% of patients versus 27% with placebo 7
• Treatment must be initiated within 24 hours of symptom onset for optimal efficacy 1, 2

Inflammation Control

• Prednisolone, etoricoxib, and indomethacin show equivalent reduction in erythema 3
• Prednisolone demonstrates superior reduction in joint swelling compared to indomethacin 3
• Naproxen shows significant clearing of inflammatory changes within 24-48 hours 4

Safety Profile Comparison

Gastrointestinal Adverse Events

• Indomethacin causes adverse events in 63% of patients versus 27% with prednisolone 6
• Non-selective NSAIDs (including naproxen and indomethacin) increase total adverse events by 90% compared to COX-2 inhibitors like etoricoxib (RR 1.9,95% CI 1.4-2.8) 7
• Naproxen causes statistically significantly less gastric bleeding than aspirin in 51Cr blood loss studies 4

Overall Tolerability

• Etoricoxib and prednisolone demonstrate similar total adverse event rates, both lower than indomethacin 3
• Corticosteroids are associated with fewer gastrointestinal adverse events than NSAIDs in comparative trials 1
• Short-term corticosteroid adverse effects include dysphoria, elevated blood glucose, and fluid retention 6

Specific Clinical Scenarios

When to Choose Prednisone Over NSAIDs

• Prednisone is the preferred first-line option in patients with renal disease (eGFR <30 mL/min), heart failure, cardiovascular disease, cirrhosis, peptic ulcer disease, or anticoagulation therapy 2, 6
• Corticosteroids are safer and lower cost compared to colchicine, with equivalent efficacy to NSAIDs 1, 6

When to Choose Etoricoxib Over Naproxen

• Etoricoxib (COX-2 selective) reduces gastrointestinal adverse events by approximately 50% compared to non-selective NSAIDs 7
• Consider etoricoxib in patients with gastrointestinal risk factors but without cardiovascular contraindications 7

Avoid Indomethacin Unless Necessary

• Despite FDA approval for acute gout, indomethacin should not be preferentially used due to higher adverse effect rates without efficacy advantage 2, 5
• If indomethacin is used, dose is 50 mg three times daily for 2-3 days, then 25 mg three times daily for 3-5 days 1

Critical Management Principles

Timing of Initiation

• Treatment effectiveness is determined more by how soon therapy is initiated than which specific NSAID is chosen 8
• Initiate treatment within 24 hours of symptom onset for optimal efficacy 1, 2
• Delaying treatment beyond 24 hours significantly reduces effectiveness 1

Duration of Therapy

• Continue full-dose NSAID therapy until the gouty attack has completely resolved 1, 2
• For prednisone, either use 5-10 days at full dose then stop abruptly, or 2-5 days at full dose followed by 7-10 day taper 2, 6

Combination Therapy for Severe Attacks

• For severe pain (≥7/10) or polyarticular involvement (≥4 joints), initiate combination therapy with colchicine plus NSAID or oral corticosteroids plus colchicine 2

Common Pitfalls to Avoid

• Never interrupt ongoing urate-lowering therapy during an acute attack—continue it throughout the flare 1, 2
• Do not initiate new urate-lowering therapy during an acute attack 2
• Avoid using aceclofenac as it lacks FDA approval and guideline support for acute gout 1, 2
• Do not preferentially select indomethacin based on historical practice patterns—it offers no advantage and causes more adverse events 2
• Inadequate response is defined as <20% pain improvement within 24 hours or <50% improvement after 24 hours—switch to another monotherapy or add a second agent 2