Cyclo-oxygenase selectivity and chemical groups of nonsteroidal anti-inflammatory drugs and the frequency of reporting hypersensitivity reactions: a case/noncase study in VigiBase

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, poor-selectivity 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.