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Risk of adverse gastrointestinal outcomes in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis

BMJ 2005; 331 doi: https://doi.org/10.1136/bmj.331.7528.1310 (Published 01 December 2005) Cite this as: BMJ 2005;331:1310

Adverse gastrointestinal outcomes and cyclo-oxygenase-2 inhibitors

EDITOR- We read with great interest the study by Hippisley-Cox et al.
1 about the gastro-intestinal risks of cyclo-oxygenase-2 (COX 2)
inhibitors and conventional non steroidal anti-inflammatory drugs. Our
goal is not to discuss the data but only to underline that the conclusion
of a lack of enhanced safety of COX 2 inhibitors was already widely
published in the literature. For example, the Laporte’s study 2, a
multicentre case-control study, found an odds ratio of 7.2 for rofecoxib.

In a case/non-case study performed in the French PharmacoVigilance
database between May 2000 and December 2002 3, we also found an increased
risk of exposure to coxibs available in France (rofecoxib; celecoxib) in
oeso-gastro-intestinal adverse drug reactions (ADRs). In fact,
epidemiological results coming from PharmacoVigilance databases are often
criticized due to their limitations: selection biases, underreporting,
“Weber” effect… This is only partly true. For example, for coxibs, it is
not possible to translate into the “real life”, the odds ratio values
found in a case/non case study, since a notoriety bias probably led to
over reporting of such oeso-gastro-intestinal ADRs.

However, comparison of
the case/non case study and the present one clearly shows that utilization
of automated ADR database (as, for example, a PharmacoVigilance database)
appears to be very useful in order to generate signals in
pharmacovigilance. Such a method (which is relatively rapid and
inexpensive) should be included in regular surveillance of drugs’ risk,
especially during the first years of drugs’ life, i.e. before than their
effects could be studied using more conventional pharmacoepidemiological
methods (like cohort or case-control studies). Thus, from a methodological
point of view, we believe that automatic analyses of PharmacoVigilance
databases should be added to the methods used for detection of ADRs. True
quantification of the risk will be performed later. This conclusion seems
important at the time where, following rofecoxib withdrawal, methods of
drugs’ surveillance are widely discussed and criticized.

The Hippisley-Cox’s study 1 and the two others cited above 2,3 also
demonstrate that the oeso-gastro-intestinal risk of coxibs is clearly
higher than that previously suggested by the sole clinical trials.

Finally, they also recall that, after randomised controlled double-blind
studies, pharmacoepidemiological studies are necessary to definitively
quantify drug’s benefit risk ratio in the real word and to verify (or not)
the conclusions of clinical trials.

Jean-Louis Montastruc, MD, PhD, pharmacoepidemiologist, Maryse
Lapeyre-Mestre, MD, PhD, pharmacoepidemiologist, Stephanie Lugardon, MD,
pharmacoépidémiologise, Agnes Sommet, MD, pharmacoépidémiologist.

Laboratoire de Pharmacologie Médicale et Clinique, Unité de
Pharmacoépidémiologie, EA 3696, IFR 126, Université Paul Sabatier, Faculté
de Médecine, 37 allées Jules-Guesde, 31000 Toulouse, France.

Address all correspondence to J.L. Montastruc montastruc@cict.fr

No conflicts of interest

References

1. Hippisley-Cox J, Coupland C, Logan R. Risk of adverse gastrointestinal
outcomes in patients taking cyclo-oxygenase-2 inhibitors or conventional
non-steroidal anti-inflammatory drugs: population based nested case-
control analysis. BMJ, 2005; 331: 1310-6

2. Laporte JR, Ibanez L, Vidal X, Vendrell L, Leone R. Upper
gastrointestinal bleeding associated with the use of NSAIDs: newer versus
older agents. Drug Saf 2004; 27: 411-20

3. Lugardon S, Lapeyre-Mestre M, Montastruc J.L. Upper gastrointestinal
adverse drug reactions and cyclo-oxygenase-2 inhibitors (celecoxib and
rofecoxib): a case/non-case study from the French Pharmacovigilance
database. Eur J Clin Pharmacol 2004; 60: 676-7

Competing interests:
None declared

Competing interests: No competing interests

09 December 2005
Jean-louis MONTASTRUC
Professor of clinical pharmacology
Maryse Lapeyre-Mestre, Stephanie Lugardon, Agnès Sommet
Université Paul Sabatier, Faculté de Médecine, 37 allées Jules-Guesde, 31000 Toulouse, France