What is the best Non-Steroidal Anti-Inflammatory Drug (NSAID) for an adult patient experiencing a gout flare?

Best NSAID for Gout Flare

No single NSAID is superior to another for treating acute gout—any NSAID at full anti-inflammatory dose is equally effective, so choose based on availability, cost, and patient-specific contraindications rather than searching for a "best" agent. 1, 2

Evidence for NSAID Equivalency

Multiple head-to-head comparisons demonstrate that different NSAIDs provide similar clinical benefits in acute gout, with no evidence supporting individual superiority in terms of pain relief or anti-inflammatory efficacy. 3, 2 A Cochrane systematic review of 28 trials (3406 participants) found no NSAID superior to another when comparing one NSAID to another NSAID across 13 trials. 2

The myth that indomethacin is the "best" NSAID for gout should be abandoned—it has no efficacy advantage over other NSAIDs and may cause more adverse effects, particularly in elderly patients. 1

FDA-Approved Options

The following NSAIDs have FDA approval specifically for acute gout and should be used at full anti-inflammatory doses: 1

• Naproxen
• Indomethacin
• Sulindac

However, any potent NSAID at full anti-inflammatory/analgesic dosing is appropriate based on international guidelines. 1, 4

COX-2 Selective Inhibitors vs Non-Selective NSAIDs

Non-selective NSAIDs and COX-2 inhibitors (COXIBs) are probably equally effective for pain relief, inflammation reduction, and treatment success. 2 However, moderate-certainty evidence shows that non-selective NSAIDs probably increase withdrawals due to adverse events (RR 2.3,95% CI 1.3 to 4.1) and total adverse events, mainly gastrointestinal (RR 1.9,95% CI 1.4 to 2.8), compared to COXIBs. 2

The COX-2 selective inhibitors etoricoxib and rofecoxib have been investigated for acute gout, but concerns about cardiovascular toxicity from both selective and non-selective COX-2 inhibitors remain, particularly problematic since gout frequently co-exists with cardiovascular disease. 3

Critical Contraindications to NSAIDs

NSAIDs should be avoided entirely in the following populations: 1, 5

• Severe renal impairment (eGFR <30 mL/min) - NSAIDs can exacerbate or cause acute kidney injury 6, 1
• Any degree of renal disease warrants extreme caution 1
• Heart failure - increased cardiovascular risks 6, 1
• Cirrhosis or hepatic impairment - NSAIDs are contraindicated 6
• Active peptic ulcer disease or recent gastrointestinal bleeding 4
• Patients on anticoagulation therapy 6, 4

When NSAIDs Are Actually NOT First-Line

Despite their widespread use, corticosteroids are now considered first-line therapy over NSAIDs due to superior safety profile, lower cost, and equal efficacy. 1 Moderate-certainty evidence from 5 trials (712 participants) shows NSAIDs and glucocorticoids are probably equally effective for pain relief (MD 0.1,95% CI -2.7 to 3.0), but NSAIDs probably result in more total adverse events (RR 1.6,95% CI 1.0 to 2.5). 2, 7

Corticosteroids are explicitly preferred over NSAIDs in: 6, 1

• Patients with renal disease
• Cardiovascular disease or heart failure
• Elderly patients (lower risk of serious adverse effects)
• Cirrhosis
• Peptic ulcer disease history

Practical Selection Algorithm

If you must use an NSAID (no contraindications present): 1, 4

1. Choose any available NSAID at full anti-inflammatory dose—there is no "best" choice
2. Consider pharmacokinetics: Rapid absorption and short half-life may help avoid accumulation in patients with subclinical renal impairment 4
3. Add proton pump inhibitor in patients with gastrointestinal risk factors 5
4. Initiate within 24 hours of symptom onset for optimal efficacy 1, 5

Common Pitfalls to Avoid

• Do not preferentially use indomethacin based on tradition—it offers no advantage and may cause more adverse effects 1
• Do not combine NSAIDs with systemic corticosteroids due to synergistic gastrointestinal toxicity 5
• Do not use NSAIDs in patients with renal impairment even if "mild"—73% of hospitalized gout patients have renal failure, yet NSAIDs were still prescribed in 80% of these cases in one study 8
• Do not assume NSAIDs are safer than corticosteroids—this outdated belief contradicts current evidence 1, 7

Bottom Line for Clinical Practice

Since no NSAID demonstrates superiority, the real clinical decision is whether to use an NSAID at all, not which NSAID to choose. 3, 2 Given that corticosteroids are equally effective, safer, and lower cost, NSAIDs should be reserved for patients without contraindications who have failed or cannot tolerate corticosteroids, or based on patient preference and previous positive experience. 1, 7