Incidence of Clinically Significant GI Events in NSAID-Treated Arthritis

Celecoxib demonstrated better overall gastrointestinal (GI) safety than ibuprofen or naproxen in patients with arthritis concurrently receiving esomeprazole and low-dose aspirin or corticosteroids, according to a multicenter, randomized, double-blind controlled trial (PRECISION; ClinicalTrials.gov identifier: NCT003462) published in Alimentary Pharmacology & Therapeutics.¹

Concern about the cardiovascular safety of coxibs led to a mandated safety trial by the US Food and Drug Administration to determine the rate of serious cardiovascular events with celecoxib compared with 2 nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). ²

Researchers also performed a prespecified secondary analysis on clinically significant GI events (CSGIEs), including bleeding, obstruction, perforation events from the stomach downward or symptomatic ulcers, and iron deficiency anemia in patients with rheumatoid arthritis or osteoarthritis receiving 100 to 200 mg celecoxib twice daily (n=8072), 600 to 800 mg ibuprofen 3 times daily (n=8040), or 375 to 500 mg naproxen twice daily (n=7969) for almost 2 years.¹

All patients received 20 to 40 mg esomeprazole daily for gastroprotection, and some patients received low-dose aspirin or corticosteroids concurrently if they were already prescribed.

The researchers found that CSGIEs occurred in 0.34%, 0.74%, and 0.66% of patients receiving celecoxib, ibuprofen, and naproxen, respectively. Less iron deficiency anemia occurred in patients receiving celecoxib than in those receiving ibuprofen or naproxen.

In patients receiving low-dose aspirin concurrently, fewer CSGIEs occurred in patients receiving celecoxib than those receiving ibuprofen (P =.03), and less iron deficiency anemia occurred in patients receiving celecoxib than in those receiving naproxen (P =.005).

However, corticosteroid use increased total GI events and CSGIEs, whereas Helicobacter pylori status had no influence on these outcomes.

The authors concluded that, “Arthritis patients taking NSAIDs plus esomeprazole have infrequent clinically significant [GI] 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.”¹

References

1. Yeomans ND, Graham DY, Husni ME, et al; on behalf of the PRECISION investigators. Randomised clinical trial: gastrointestinal events in arthritis patients treated with celecoxib, ibuprofen or naproxen in the PRECISION trial [published online April 17, 2018]. Aliment Pharmacol Ther. doi: 10.1111/apt.14610
2. Nissen SE, Yeomans ND, Solomon DH, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs in patients with chronic arthritis.  N Engl J Med. 2016;375:2519-2529.