What is the preferred treatment between naproxen (Nonsteroidal Anti-Inflammatory Drug (NSAID)) and celecoxib (Cyclooxygenase-2 (COX-2) inhibitor) for arthritis?

Naproxen vs Celecoxib for Arthritis

Celecoxib is the preferred choice for most arthritis patients due to superior gastrointestinal safety while providing equivalent pain relief and anti-inflammatory efficacy compared to naproxen. 1, 2

Efficacy: Equivalent Between Both Agents

Both medications demonstrate comparable effectiveness for arthritis treatment across multiple conditions:

• Osteoarthritis: Celecoxib 100-200 mg twice daily shows similar efficacy to naproxen 500 mg twice daily in reducing pain and improving function, with improvements evident within 24-48 hours and sustained throughout treatment 1, 3

• Rheumatoid Arthritis: Both agents produce equivalent anti-inflammatory and analgesic effects, with maximal activity within 2 weeks of initiation 1, 4

• Ankylosing Spondylitis: Head-to-head trials demonstrate no efficacy differences between celecoxib and naproxen for pain or stiffness, with the American College of Rheumatology recommending against designating any particular NSAID as preferred based on efficacy alone 5

Safety Profile: Celecoxib Demonstrates Clear Advantages

Gastrointestinal Safety

Celecoxib provides substantially better GI safety than naproxen, even when both are co-prescribed with proton pump inhibitors:

• In the PRECISION trial with all patients receiving esomeprazole gastroprotection, clinically significant GI events (bleeding, perforation, obstruction, symptomatic ulcers) occurred in 0.34% on celecoxib versus 0.66% on naproxen (HR 0.51,95% CI 0.32-0.81, p=0.004) 2

• Iron deficiency anemia occurred significantly less with celecoxib: HR 0.40 (95% CI 0.25-0.62, p<0.0001) versus naproxen 2

• Endoscopic ulcer rates: celecoxib 4-6% across all doses versus naproxen 26% (p<0.001) 4

• This GI advantage persists even in patients taking concurrent low-dose aspirin 2

Cardiovascular Safety

The PRECISION trial definitively established celecoxib's cardiovascular non-inferiority to naproxen:

• Celecoxib 100 mg twice daily met all prespecified non-inferiority criteria for the composite cardiovascular endpoint (CV death, MI, stroke) compared to naproxen 1

• ITT analysis: 2.3% events with celecoxib vs 2.5% with naproxen (HR 0.93,95% CI 0.76-1.13) 1

• All-cause mortality through 30 months: 1.6% celecoxib vs 2.0% naproxen 1

Blood Pressure Effects

• Celecoxib decreased mean 24-hour systolic blood pressure by 0.3 mmHg, while naproxen increased it by 1.6 mmHg (difference 1.8 mmHg, though not statistically significant) 1

Clinical Decision Algorithm

Start with celecoxib 100 mg twice daily (or 200 mg once daily) for:

• All arthritis patients without contraindications 1
• Particularly those with GI risk factors (age >65, prior ulcer history, concurrent anticoagulation, corticosteroid use) 6
• Patients with cardiovascular disease or risk factors (celecoxib demonstrated non-inferiority) 1
• Patients requiring concurrent low-dose aspirin 2

Consider naproxen 375-500 mg twice daily only when:

• Celecoxib is contraindicated (sulfonamide allergy)
• Cost considerations are paramount and patient has no GI risk factors
• Patient has demonstrated superior individual response to naproxen

Always co-prescribe:

• Proton pump inhibitor (esomeprazole 20-40 mg daily) for all patients on either agent 1, 2

Important Caveats

• The PRECISION trial used predominantly celecoxib 100 mg twice daily (only 5.8% dose-escalated to 200 mg twice daily), so cardiovascular safety data at higher doses remain less robust 1

• Both agents carry standard NSAID warnings for cardiovascular thrombotic events, though celecoxib demonstrated non-inferiority 1

• Corticosteroid co-administration increases GI event risk with both agents 2

• H. pylori status does not influence GI event rates when PPIs are used 2