Celecoxib gastrointestinal complications

In the second analysis, data from 14 studies of the efficacy of celecoxib in osteoarthritis or rheumatoid arthritis in 11 007 patients were pooled (80,81). Gastrointestinal complications (bleeding, obstruction, or perforation) occurred in 0.2% of the patients per year of exposure to celecoxib and in 1.7% per year of exposure to traditional NSAIDs. The absolute risk reduction was 1.5% (Cl = 0.4, 2.6). This study, too, had some limitations. In fact, ulcer complication was not the specified end-point of the studies that were pooled, and about 15% of celecoxib-treated patients took a dose below that indicated for arthritis. 

Two large trials, the Vioxx Gastrointestinal Outcomes Research (VIGOR) study and the Celecoxib Long-term Arthritis Safety Study (CLASS), compared selective COX-2 inhibitors and traditional, non-selective NSAID therapy in terms of their ability to prevent clinical PUD (i.e., symptomatic ulcers and ulcer complications). VIGOR (9-month median follow-up) demonstrated that rofecoxib (50 mg daily) therapy was significantly more efficacious than naproxen.28 The CLASS study (6-month median follow-up) found that high-dose celecoxib (400 mg twice daily) was superior to non-selective NSAID therapy (either ibuprofen 800 mg three times daily or diclofenac 75 mg twice daily).29... 

Meloxicam is an enolcarboxamide related to piroxicam that preferentially inhibits COX-2 over COX-1, particularly at its lowest therapeutic dose of 7.5 mg/d. It is not as selective as celecoxib and may be considered "preferentially" selective rather than "highly" selective. The drug is popular in Europe and many other countries for the treatment of most rheumatic diseases and approved for treatment of osteoarthritis in the USA. It is associated with fewer clinical gastrointestinal symptoms and complications than piroxicam, diclofenac, and naproxen. Similarly, while meloxicam is known to inhibit synthesis of thromboxane A2, even at supratherapeutic doses its blockade of thromboxane A2 does not reach levels that result in decreased in vivo platelet function (see common adverse effects above). 

In conclusion, clinical trials have shown that COX-2-selective NSAIDs seem to be less toxic to the gastrointestinal mucosa than traditional ones. However, life-threatening ulcer complications have been reported in patients taking both celecoxib (81,96,97) and rofe-coxib (79). The FDA and other regulatory authorities require that drug information sheets for celecoxib and rofecoxib carry gastrointestinal ulcer warnings similar to those for older NSAIDs. 

Goldstein JL, Silverstein FE, Agrawal NM, Hnbbard RC, Kaiser J, Maurath CJ, Verbnrg KM, Geis GS. Reduced risk of upper gastrointestinal ulcer complications with celecoxib, a novel COX-2 inhibitor. Am J Gastroenterol 2000 95(7) 1681-90. 

Gastrointestinal Nimesulide is a frequently used NSAID in Italy, whereas it is less frequently used in other European countries. In a cohort and nested case-control study among NSAID users, the risk of upper GI complications was compared for users of nimesulide and other commonly used NSAIDs in Italy, using data from 2001 to 2008 from regional health databases. The relative risk of upper GI complications was 3.28 for current use of NSAIDs (95%CI 2.86-3.76), was <2 for rofecoxib, celecoxib and nimesulide, 2 to <5 for naproxen, ibuprofen, diclofenac, etoricoxib and meloxicam, and >5 for ketoprofen, piroxicam and ketorolac [52 ]. 

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