AIMS: This study aimed to provide a credible and comprehensive safety assessment on panoramic adverse events (AEs) associated with onasemnogene abeparvovec (OA) therapy. METHODS: Disproportionality analysis was conducted, using reporting odds ratio (ROR) method in tandem with Bayesian confidence propagation neural network (BCPNN). Two-sample Kolmogorov–Smirnov test was applied to analyze the distribution time-to-onset (TTO) of adverse events as TTO algorithm to determine pharmacovigilance signals which were inconclusive by BCPNN. Omega shrinkage was conducted to investigate drug-drug interaction between OA and its concomitant drugs. Multi-factor regression was conducted to evaluate association between OA-induced adverse events and outcomes of the reports. RESULTS: In total, 1,033 cases of OA treated patients were included for the study, and 124 pharmacovigilance signals were confirmed by ROR in tandem with BPCNN, most of which were previously unrecorded by the package-insert. Meanwhile, there were 13 signals including cardiac arrest, multiple organ dysfunction syndrome and signals referring to respiratory disorders, were determined by ROR in tandem with the TTO algorithm. Four symptoms including cyanosis, cardiac arrest, hypoxia and respiratory failure, needed to be closely monitored, due to the association with mortal outcomes. CONCLUSIONS: This study might enhance the understanding of safety profile of OA Healthcare providers should be vigilant about severe adverse reactions when administrating OA.

Abstract Aim: we sought to estimate the association between hypoglycemic medications especially sodium-glucose co-transporter-2 inhibitors (SGLT2i) and osteomyelitis based on the FDA adverse event reporting system (FAERS). Methods: Publicly available FAERS data were analyzed using reporting odd ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. The developing trend of ROR were revealed by series of calculation based on accumulating dataset quarter by quarter. Results: Ketoacidosis, infections, peripheral ischemia, renal impairment, inflammation including osteomyelitis might more likely to occur among SGLT2i users, especially canagliflozin. Osteomyelitis and cellulitis are AEs unique to canagliflozin. Among 2,888 osteomyelitis-related reports referring to glucose lowering medications, 2,333 cases were associated with SGLT2i, mostly with canagliflozin counting 2,283 which generated an ROR value of 360.89 and a lower limit of information component (IC025) of 7.79. No BCPNN-positive signal could be generated for drugs other than insulin, canagliflozin or drug groups excluding canagliflozin. Reports referring to insulin could generate BCPNN-positive signals during the entire timespan from 2004 to 2021, while BCPNN-positive signal emerged since second quarter (Q2) of 2017, four years since the approval of SGLT2i in Q2 of 2013, for canagliflozin and drug groups containing canagliflozin. Conclusion: This data mining revealed that strong association between canagliflozin treatment and developing osteomyelitis which might be a precursor to lower extremity amputation. Further study with updated data is needed to better characterize the risk of osteomyelitis associated with SGLT2i.