Randomised clinical trial: gastrointestinal events in arthritis patients treated with celecoxib, ibuprofen or naproxen in the PRECISION trial

Summary Aim To evaluate GI safety of celecoxib compared with 2 nonselective (ns) NSAID s, as a secondary objective of a large trial examining multiorgan safety. Methods This randomised, double‐blind controlled trial analysed 24 081 patients. Osteoarthritis or rheumatoid arthritis patients, needing ongoing NSAID treatment, were randomised to receive celecoxib 100‐200 mg b.d., ibuprofen 600‐800 mg t.d.s. or naproxen 375‐500 mg b.d. plus esomeprazole, and low‐dose aspirin or corticosteroids if already prescribed. Clinically significant GI events ( CSGIE —bleeding, obstruction, perforation events from stomach downwards or symptomatic ulcers) and iron deficiency anaemia ( IDA ) were adjudicated blindly. Results Mean treatment and follow‐up durations were 20.3 and 34.1 months. While on treatment or 30 days after, CSGIE occurred in 0.34%, 0.74% and 0.66% taking celecoxib, ibuprofen and naproxen. Hazard ratios ( HR ) were 0.43 (95% CI 0.27‐0.68, P = 0.0003) celecoxib vs ibuprofen and 0.51 (0.32‐0.81, P = 0.004) vs naproxen. There was also less IDA on celecoxib: HR 0.43 (0.27‐0.68, P = 0.0003) vs ibuprofen; 0.40 (0.25‐0.62, P < 0.0001) vs naproxen. Even taken with low‐dose aspirin, fewer CSGIE occurred on celecoxib than ibuprofen ( HR 0.52 [0.29‐0.94], P = 0.03), and less IDA vs naproxen (0.42 [0.23‐0.77, P = 0.005]). Corticosteroid use increased total GI events and CSGIE . H. pylori serological status had no influence. Conclusions Arthritis patients taking NSAID s plus esomeprazole have infrequent clinically significant gastrointestinal events. Co‐prescribed with esomeprazole, celecoxib has better overall GI safety than ibuprofen or naproxen at these doses, despite treatment with low‐dose aspirin or corticosteroids.