Background The US Food and Drug Administration AE reporting system (FAERS) contains information for all marketed and investigational drugs in the US and provides sufficient safety data for disproportionality analysis for specific events associated with the use of drugs.
Objectives To perform the disproportionality analysis of anaphylactic reactions among users of abatacept (ABA) and other biologics for the treatment of RA, utilizing data from FAERS.
Methods The disproportionality of anaphylactic-type reactions associated with ABA and other biologics was analysed using cumulative safety data retrieved from the FAERS database up to 22 June 2015. The preferred terms in the Standardized Medical Dictionary for Regulatory Activities Queries (SMQ) for anaphylactic reactions (narrow terms) were used for the database search and included anaphylactic reaction, anaphylactic shock, anaphylactic transfusion reaction, anaphylactoid reaction, anaphylactoid shock, circulatory collapse, Kounis syndrome, shock and type I hypersensitivity. Biologics searched for included ABA, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab and tocilizumab. Penicillin was included as positive control due to its known association with anaphylactic-type reactions.1 The disproportionality report is defined as a ratio of observed to expected frequencies of reports mentioning both the targeted drug (Y) and targeted AE (X). The observed frequency is calculated as the number of reports for event X with drug Y, and the expected frequency is the number of drug–event combinations of interest that would be expected if the event of interest (X) is reported independently of the drug of interest (Y). The disproportionality measure (i.e. observed/expected) referred to by empirical Bayesian geometric mean and the corresponding 90% CI (EB05, EB95) were calculated. The threshold of EB05 ≥2 for any drug–event pair identifies drug–event combinations that are reported at least twice as often as all other drug–event combinations.
Results Among the evaluated drugs, the EB05 scores for anaphylactic reaction, anaphylactic shock and anaphylactoid reaction were the highest with penicillin use, as expected (Table). The EB05 scores for all drug–event pairs for ABA were <2. The EB05 scores for drug–event pairs for other biologics were <2 except anaphylactic reaction and anaphylactoid reaction for infliximab, and anaphylactic reaction for tocilizumab.
Conclusions Overall, there were few signals of disproportionality for anaphylactic-type reactions with the use of abatacept and other biologics for RA, with the exceptions of anaphylactic reaction and anaphylactoid reaction for infliximab and anaphylactic reaction for tocilizumab. This observation is consistent with the results reported from clinical studies that were documented in the prescribing information for abatacept and other respective drugs for RA.2–4
Penicillin prescribing information. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050638s016lbl.pdf. Accessed 14 January 2016.
Orencia prescribing information. http://packageinserts.bms.com/pi/pi_orencia.pdf. Accessed 13 January 2016.
Remicade prescribing information. http://www.remicade.com/shared/product/remicade/prescribing-information.pdf. Accessed 13 January 2016.
Actemra prescribing information. http://www.gene.com/download/pdf/actemra_prescribing.pdf. Accessed 13 January 2016.
Disclosure of Interest H. Yu Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, A. Dominique Employee of: Bristol-Myers Squibb, T. A. Simon Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, A. Gomez Shareholder of: Bristol-Myers Squibb, GlaxoSmithKline, Employee of: Bristol-Myers Squibb