Cyclooxygenase selectivity and chemical subgroup of non-steroidal anti-inflammatory drugs and frequency of spontaneous reporting of hypersensitivity reactions: A case/non-case study in Vigibase

Abstract

Background: Useofnon-steroidal anti-inflammatory drugs(NSAIDs) has been associated with many adverse events, including hypersensitivity reactions (HSRs), such as angioedemaand urticaria. However, no studies have investigated whether cyclooxygenase (COX) enzyme selectivity and/or chemical subgroups are associated with a difference in HSRs. Objectives: To describe and compare the frequency of HSRs among NSAIDs based on cyclooxygenase selectivity and chemical subgroups. Methods: A case/non-case study was performed using data from the World Health Organization global database of Individual Case Safety Report (ICSR), VigiBase, containing over 13 million ICSRs submitted by the participating member states enrolled 'under WHO's international drug monitoring program by June 2016. This study was nested among ICSRs where NSAIDs were a suspected drug. Cases were ICSRs mentioning HSRs (urticaria, angioedema, anaphylactic shock, anaphylactic reaction, anaphylactoid shock, and anaphylactoid reaction), whereas noncases were all ICSRs without HSRs. Based on the ratio of inhibitory concentration 80% of COX-1/COX-2, NSAIDs were categorized into coxibs, non-coxibNSAIDs with COX-2 preference, NSAIDs with poor selectivity, and NSAIDs with unknown selectivity. Only ICSRs with complete information on age and sex, and NSAIDs with first market authorization from 1978 onward were included. RORs and 95% confidence intervals (95% CIs) to assess the association between NSAIDs and the reporting of HSRs were calculated using logistic regression analysis. Results: We identified 16 289 HSR cases and 160 319 non-cases among ICSRs involving NSAIDs. Non-coxib NSAIDs with COX-2 preference, NSAIDs with poor selectivity, and NSAIDs with unknown selectivity were all associated with an increased reporting of HSRs (age-and sex-adjusted ROR 1.70, 95% CI: 1.61-1.79; age-and sexed justed 2.19, 95% CI: 2.11-2.77; and age-and sex-adjusted 1.26, 95% CI: 1.03-1.54, respectively) compared with coxibs. Conclusions: HSRs were more often reported for NSAIDs with poor selectivity, non-coxib NSAID with COX-2 preference, and NSAIDs with unknown selectivity compared with coxibs.