OBJECTIVES: Infections have been reported as serious adverse events with biologics. Biosimilar pharmacosurveillance has, to date, been limited, but there may be differences in the safety profiles. The objective of this study is to compare the safety profile of biologics (adalimumab, etanercept and infliximab) and their biosimilars (adalimumab-adaz, etanercept-szzs and infliximab-dyyb) using spontaneously reported infections from FDA Adverse Event Reporting System (FAERS).

METHODS: FAERS files from 1998 to 2022 were used to obtain case reports for all drugs. After standardizing and mapping of all infections and filtering duplicate reports, disproportionality analysis was used to detect signals by calculating proportional reporting ratio (PRR) and reporting odds ratio (ROR) comparing each biosimilar to the three biologics. The ROR is the odds of a certain event occurring with a drug, compared to the odds of the same event occurring with all other drugs in the database. The PRR is the proportion of spontaneous reports for a given drug that are linked to a specific adverse outcome, divided by the corresponding proportion for all or several other drugs. A statistically significant signal was defined an ROR >1 or a PRR > 2.

RESULTS: We identified 4702 reports of infections for biosimilars and 280,444 for the biologics. There were two significant (numerically and statistically), ROR infection signals indicating biosimilar greater infections, for Infliximab-dyyb [ROR (95%): 1.49 (1.43-1.55)] and Etanercept-szzs [ROR (95%): 2.10 (1.96-2.26)]. The Adalimumab-adaz signal was not significant [ROR (95%): 1.04 (0.90-1.20)] No significant signals were detected using the PRR. PRR for Adalimumab-adaz is 1.03 [(0.99-1.07)], Infliximab-dyyb is 1.34 [(1.29-1.40)], and Etanercept-szzs is 1.68 [(1.62-1.75)].

CONCLUSIONS: Biosimilars had some associations with infections (increased signals). However, a signal is not a causal association between a drug and adverse event. Therefore, a formal epidemiological study is necessary.