Do proton-pump inhibitors confer additional gastrointestinal protection in patients given celecoxib?

Celecoxib has a superior upper-gastrointestinal (GI) safety profile compared with nonselective nonsteroidal antiinflammatory drugs (NS-NSAIDs). It is unclear whether the utilization of a proton-pump inhibitor (PPI) with celecoxib confers additional protection in elderly patients. We assessed the association between GI hospitalizations and use of celecoxib with a PPI versus celecoxib alone, and NS-NSAIDs with a PPI or NS-NSAIDs alone in elderly patients.

We conducted a population-based retrospective cohort study using the government of Quebec health services administrative databases. Elderly patients were included at their first dispensing date for celecoxib or an NS-NSAID between April 1999 and December 2002. Prescriptions were separated into 4 groups: celecoxib, celecoxib plus PPI, NS-NSAIDs, and NS-NSAIDs plus PPI. Cox regression models with time-dependent exposure were used to compare the hazard rates of GI hospitalization between the 4 groups adjusting for patient characteristics at baseline.

There were 1,161,508 prescriptions for celecoxib, 360,799 for celecoxib plus PPI, 715,176 for NS-NSAIDs, and 148,470 for NS-NSAIDs plus PPI. The adjusted hazard ratios (HRs; 95% confidence intervals [95% CIs]) were 0.69 (0.52-0.93) for celecoxib plus PPI versus celecoxib, 0.98 (0.67-1.45) for NS-NSAIDs plus PPI versus celecoxib, and 2.18 (1.82-2.61) for NS-NSAIDs versus celecoxib. Subgroup analyses showed that use of a PPI with celecoxib may be beneficial in patients ages >/=75 years but was not better than celecoxib alone among those ages 66-74 years (HR 0.98, 95% CI 0.63-1.52).

Addition of a PPI to celecoxib conferred extra protection for patients ages >/=75 years. PPI did not seem necessary with celecoxib for patients ages 66-74 years.