Differences in safety of non-steroidal anti-inflammatory drugs in patients with osteoarthritis and rheumatoid arthritis : a randomized clinical trial

OBJECTIVE: To determine relative cardiovascular, gastrointestinal and renal safety of celecoxib, compared with ibuprofen and naproxen during chronic use in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: 24,081 patients with OA or RA at moderate or high cardiovascular risk enrolled internationally in a double-blind randomized controlled trial. Interventions included celecoxib 100-200mg bid, ibuprofen 600-800mg tid, or naproxen 375-500mg bid. Main outcomes comprised first occurrence of major adverse cardiovascular events (MACE), gastrointestinal events, renal events, and mortality. RESULTS: OA subgroup participants had significantly reduced risk of MACE comparing celecoxib to ibuprofen (HR 0.84, 95% CI 0.72 - 0.99), but no significant difference comparing celecoxib to naproxen. In the RA subgroup, comparison of celecoxib vs ibuprofen and celecoxib vs naproxen for MACE events revealed HR of 1.06 (95% CI 0.69 - 1.63) and 1.22 (95% CI 0.78 - 1.92), respectively. The HR for gastrointestinal events in OA comparing celecoxib with ibuprofen was 0.68 (95% CI 0.51 - 0.91) and with naproxen 0.73 (95% CI 0.55 - 0.98). Duplicate comparisons in RA revealed HRs of 0.48 (95% CI 0.22 - 1.07) and 0.54 (95% CI 0.24 - 1.24), respectively. In OA, comparing celecoxib to ibuprofen for risk of renal events showed an HR of 0.58 (95% CI 0.40-0.82). In RA, celecoxib associated with significantly lower mortality than naproxen (HR 0.47, 95% CI 0.25 - 0.88). CONCLUSIONS: Celecoxib at approved dosages produced similar or lower cardiovascular, gastrointestinal, and renal risk for adverse events compared with ibuprofen and naproxen in OA and RA.