Abstract:
To date, no reports of hypersensitivity reactions (HSRs) among nonsteroidal
anti-inflammatory drugs (NSAIDs) according to cyclo-oxygenase (COX) selectivity
and chemical groups have been published in a single study. The present study
assessed the reporting frequency of HSRs for NSAIDs based on their relative inhibitory potency toward COX enzymes and chemical groups, including the presence/
absence of a functional sulfonamide group, in strata observed 5 years after market
authorization. A case/noncase study was performed among individual case safety
reports (ICSRs) with NSAIDs as suspected drugs in VigiBase, the WHO spontaneous
reporting database. Cases were ICSRs mentioning angioedema and anaphylactic/
anaphylactoid shock conditions, while noncases were ICSRs without HSRs. NSAIDs
were categorized into (i) NSAIDs with high COX-2 selectivity (coxibs), (ii) noncoxib
NSAIDs with COX-2 preference, (iii) NSAIDs with poor selectivity, or (iv) NSAIDs
with unknown selectivity. Chemical groups were defined based on the Anatomical
Therapeutic Chemical classification system and the presence/absence of a functional sulfonamide group. Reporting odds ratios (RORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression analysis. We identified
13 229 cases and 106 444 noncases. In the first 5 years after marketing, poorselectivity NSAIDs and acetic acid derivatives were associated with the highest
ROR of HSRs (age- and sex-adjusted ROR 2.12, 95% CI 1.98–2.28; and ROR 2.21,
95% CI 1.83–2.66, respectively) compared with coxibs, and sulfonamide NSAIDs
were associated with the highest ROR of HSRs compared with nonsulfonamide
NSAIDs (age- and sex-adjusted ROR 1.38, 95% CI 1.29–1.47). After the first
5 years of marketing, most of the RORs returned to approximately 1.
Keywords
a sulfonamide functional
group,
chemical groups,
cyclo-oxygenase selectivity,
hypersensitivity reactions,
nonsteroidal anti-inflammatory drugs,
spontaneous reporting
