Rofecoxib gastrointestinal complications

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... 

Overall, confirmed upper gastrointestinal events occurred in 177 patients, 56 with rofecoxib n — 4047), and 121 in those taking naproxen n — 4029). In 53 of these patients (16 taking rofecoxib and 37 taking naproxen) the event was complicated. That means that during a median follow-up of 9.0 months, there were 2.1 confirmed gastrointestinal events per 100 patient-years with rofecoxib compared with 4.5 per 100 patient-years with naproxen (RR = 0.5 95% Cl = 0.2, 0.8). The respective rates of complicated ulcers (perforation, obstruction, and bleeding) were 0.6 per 100 patient-years and 1.4 per 100 patient-years (RR = 0.4 95% Cl = 0.2, 0.8). 

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. 

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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