A randomized, controlled comparison of ibuprofen at the maximal over-the-counter dose compared with prescription-dose celecoxib on upper gastrointestinal mucosal injury.
OBJECTIVE
Ibuprofen is a well-tolerated nonsteroidal anti-inflammatory drug (NSAID), particularly at over-the-counter (OTC) doses. Cyclooxygenase 2 (COX-2)-selective inhibitors cause less ulceration than prescription-dose nonselective NSAIDs. We compared endoscopic injury related to nonprescription ibuprofen doses with celecoxib, also comparing prescription doses of naproxen with placebo as a positive control.


METHODS
The study was a randomized, placebo-controlled, double blind, double-dummy endoscopic evaluation with concealed allocation. A 2-way crossover with a 4-5-week washout period was used. Participants were healthy adults with normal baseline findings from endoscopy. Ninety-five subjects were randomly assigned, and 79 subjects completed both study phases. Age distribution was reflective of the target population of the OTC agent. Twenty percent were infected with Helicobacter pylori, and 79% and 67% had a current or past medical problem, respectively. Qualifying subjects, stratified by the presence or absence of H. pylori infection (n = 20), were randomly assigned to 1 of the 4 sequences (phase I/II) as follows: ibuprofen/celecoxib; celecoxib/ibuprofen, naproxen/placebo, or placebo/naproxen. Primary end points were the frequency of endoscopic ulcers and erosions in the groups administered: (1) celecoxib vs. ibuprofen and (2) naproxen vs. placebo.


RESULTS
In celecoxib-treated subjects, 2.6% developed ulcers compared with 17.9% of those treated with ibuprofen (P = 0.056). Naproxen treatment was associated with a significantly greater ulceration rate compared with placebo.


CONCLUSIONS
Short-term use of the nonselective COX inhibitors ibuprofen and naproxen is associated with a greater risk for endoscopic mucosal injury compared with the COX-2-selective inhibitor celecoxib or placebo. A prospective analysis appropriately powered to address the incidence of clinically significant gastroduodenal ulceration associated with the short-term use of these agents would be required to further define the clinical relevance of these findings.
Scheiman
James M
JM
Department of Internal Medicine, University of Michigan, Ann Arbor, 48109-0362, USA. jscheima@umich.edu
Cryer
Byron
B
Kimmey
Michael B
MB
Rothstein
Richard I
RI
Riff
Dennis S
DS
Wolfe
Michael M
MM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000068579:Celecoxib; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage* / Q000009:adverse effects; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009288:Naproxen / Q000008:administration & dosage* / Q000009:adverse effects; D004366:Nonprescription Drugs; D011336:Probability; D011720:Pyrazoles; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects
D004366:Nonprescription Drugs; D011720:Pyrazoles; D013449:Sulfonamides; D009288:Naproxen; D000068579:Celecoxib; D007052:Ibuprofen