At approved doses, the use of the nonsteroidal anti-inflammatory drug (NSAID) celecoxib in patients with osteoarthritis (OA) and rheumatoid arthritis (RA) was associated with a similar or a lower risk for cardiovascular (CV), gastrointestinal (GI), and renal adverse events (AEs) compared with ibuprofen and naproxen, according to the results of an international, double-blind, randomized, controlled trial published in Arthritis & Rheumatology.
The investigators of the PRECISION trial (Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen; ClinicalTrials.gov identifier: NCT00346216) sought to determine the relative CV, GI, and renal safety of celecoxib taken chronically compared with ibuprofen and naproxen in patients with OA and RA.
A total of 24,081 participants with OA (n=21,645) or RA (n=2436) who were at moderate to high CV risk were enrolled in the study. In patients with OA, 7259 were treated with celecoxib, 7208 were treated with ibuprofen, and 7178 were treated with naproxen. In patients with RA, 813 were treated with celecoxib, 832 were treated with ibuprofen, and 791 were treated with naproxen.
Doses evaluated were celecoxib 100 to 200 mg twice daily, ibuprofen 600 to 800 mg 3 times daily, and naproxen 375 to 500 mg twice daily. Main study outcomes included first occurrence of a major adverse cardiac event (MACE), GI events, renal events, and mortality.
Patients in the OA subgroup had a significantly reduced risk for MACE when treated with celecoxib vs ibuprofen (hazard ratio [HR], 0.84; 95% CI, 0.72-0.99) but no significantly decreased risk when treated with celecoxib vs naproxen.
In the RA subgroup, the HRs for MACE in patients treated with celecoxib vs ibuprofen and celecoxib vs naproxen were 1.06 (95% CI, 0.69-1.63) and 1.22 (95% CI, 0.78-1.92), respectively.
Regarding GI events in the OA cohort, the HR was 0.68 (95% CI, 0.51-0.91) with celecoxib vs ibuprofen and 0.73 (95% CI, 0.55-0.98) with celecoxib vs naproxen. In the RA cohort, the HRs for GI events were 0.48 (95% CI, 0.22-1.07) with celecoxib vs ibuprofen and 0.54 (95% CI, 0.24-1.24) with celecoxib vs naproxen.
With respect to risk for renal events in the OA subgroup, celecoxib vs ibuprofen demonstrated an HR of 0.58 (95% CI, 0.40-0.82). Moreover, in the RA subgroup, celecoxib was linked to significantly lower mortality compared with naproxen (HR, 0.47; 95% CI, 0.25-0.88).
The results of these subgroup analyses of the PRECISION trial confirmed no increased CV risk with celecoxib use. However, celecoxib was associated with slight reductions in the risk for several other outcomes compared with the other commonly used NSAIDs.
These data that demonstrate differential safety across NSAIDs might warrant new recommendations for the optimal use of these agents.
Solomon DH, Husni ME, Wolski KE, et al; PRECISION Trial Investigators. Differences in safety of non-steroidal anti-inflammatory drugs in patients with osteoarthritis and rheumatoid arthritis: a randomized clinical trial [published online December 20, 2017]. Arthritis Rheumatol. doi:10.1002/art.40400