Hospitalization for peptic ulcer and bleeding in users of selective COX-2 inhibitors and nonselective NSAIDs with special reference to celecoxib.
OBJECTIVE
To assess the relative incidence of peptic ulcer bleeding and perforation (PUBP) in users of selective cyclooxygenase-2 (COX-2) inhibitors and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs).


METHODS
This was a retrospective case-control study based on insurance claims, with chart review to confirm cases. The base population consisted of 2.2 million adult users of celecoxib, diclofenac, ibuprofen, naproxen, rofecoxib, or valdecoxib who were covered by commercial health insurance in the United States from 1999-2003. For 790 persons hospitalized for PUBP and 7887 controls, most recent NSAID/COX-2 use and a variety of medical and pharmacy risk factors were ascertained from the insurance files and analyzed by conditional logistic regression. The main outcome measure was the odds ratio (OR) associated with use of each drug by comparison to naproxen, and in successive intervals after last dispensing.


RESULTS
Hospitalization for PUBP was highest from the date of NSAID/COX-2 dispensing through the end of an exposure period that corresponded to the days supply; the rate dropped steadily thereafter. The covariate-adjusted ORs by comparison to naproxen were: ibuprofen 0.86 (95% confidence interval (CI) 0.68, 1.09), rofecoxib 0.79 (0.62, 1.02), diclofenac 0.66 (0.47, 0.94), valdecoxib 0.50 (0.26, 0.97), and celecoxib 0.45 (0.35, 0.58). The nonselective NSAIDs had an OR for PUBP of 1.51 (1.26, 1.98) compared to the selective COX-2 inhibitors.


CONCLUSIONS
Nonselective NSAIDs convey half again as much risk of hospitalization for PUBP as do COX-2 inhibitors. Celecoxib users had about half the hospitalization rate of users of naproxen.
Patterson
M Kay
MK
i3 Drug Safety, Waltham, MA, USA.
Castellsague
Jordi
J
Walker
Alexander M
AM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016022:Case-Control Studies; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects*; D005260:Female; D006760:Hospitalization / Q000639:trends*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010437:Peptic Ulcer / Q000139:chemically induced* / Q000453:epidemiology; D010438:Peptic Ulcer Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D011720:Pyrazoles / Q000009:adverse effects*; D012189:Retrospective Studies; D013449:Sulfonamides / Q000009:adverse effects*; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib