Upper gastrointestinal adverse drug reactions and cyclo-oxygenase-2 inhibitors (celecoxib and rofecoxib): a case/non-case study from the French Pharmacovigilance Database.
OBJECTIVE
To evaluate the gastrointestinal safety of cyclo-oxygenase-2 inhibitors under their real conditions of use. DESIGN. Case/non-case study.


METHODS
Adverse drug reactions (ADRs) in adults recorded in the French Pharmacovigilance Database between 25 May 2000 and 31 December 2002.


METHODS
Cases were all reports of "serious" oeso-gastro-duodenal ADRs (oeso-gastro-duodenal ulcers, oesophagitis, gastritis, duodenitis). Five non-cases were randomly selected for one case from all other non oeso-gastro-duodenal reports in the database after matching them for age, gender and period of occurrence.


METHODS
Coxib exposure was compared among cases and non-cases, with adjustment for matching factors: French Regional Pharmacovigilance Centres that collected ADRs, reporter health professional's characteristics and exposures to non-selective non-steroidal anti-inflammatory, aspirin, anticoagulant, antiplatelet and gastroprotective drugs.


RESULTS
Included in the study were 505 cases and 2,525 non-cases. A positive association was found between occurrence of oeso-gastro-duodenal ADRs and coxib (adjusted odds ratio 14.9 [95% CI 9.3-23.7]), diclofenac (9.2 [3.8-22.2]), ibuprofen (7.3 [3.2-16.6]) or oxicam (25.3 [11.9-53.6]) use.


CONCLUSIONS
Despite the compulsory limits of the case/non-case methodology, the present study shows that coxibs did induce "serious" gastrointestinal ADRs in real clinical practice. These results underline the need for pharmacoepidemiological studies under real conditions of use in order to verify (or not) the conclusions of clinical trials.
Lugardon
S
S
Service de Pharmacologie Clinique, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d'Information sur le Médicament, Unité de Pharmacoépidémiologie, EA 3696, IFR 126, Faculté de Médecine, Toulouse, France.
Lapeyre-Mestre
M
M
Montastruc
J L
JL
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D016208:Databases, Factual; D004382:Duodenitis / Q000139:chemically induced / Q000453:epidemiology; D004941:Esophagitis / Q000139:chemically induced / Q000453:epidemiology; D005260:Female; D005602:France / Q000453:epidemiology; D005756:Gastritis / Q000139:chemically induced / Q000453:epidemiology; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D007783:Lactones / Q000009:adverse effects*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011720:Pyrazoles / Q000009:adverse effects*; D012189:Retrospective Studies; D013449:Sulfonamides / Q000009:adverse effects*; D013450:Sulfones / Q000009:adverse effects*; D014456:Ulcer / Q000139:chemically induced / Q000453:epidemiology; D041742:Upper Gastrointestinal Tract / Q000187:drug effects*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib