(A-251) Safety signal monitoring of an anti-COVID-19 drug in the MID-NET® in Japan

Background: Safety information for drugs and vaccines approved under the expedited pathway for responding to public emergency due to coronavirus disease 2019 (COVID-19) was limited at the time of approval. A rapid and continuous accumulation of safety information for those products at an early stage after approval was essential to facilitate its proper use in clinical practice.

Objectives: To rapidly and continuously monitor safety signals of an anti-COVID-19 drug based on real-world data from the Medical Information Database NETwork (MID-NET®) in Japan.

Methods: We employed a new user cohort design and selected patients prescribed a combination of tixagevimab and cilgavimab (tix/cil) as exposure and those prescribed two controls (peramivir and the combination of casirivimab and imdevimab (cas/imd)). We monitored 46 outcomes related to liver and kidney functions, blood system, and some biomarkers defined based on laboratory test results. Statistical analyses were performed to calculate for the age and sex-adjusted hazard ratio (aHR), with a 95% confidence interval (CI) of exposure to control estimated by Cox proportional hazards model. The analysis was conducted by using a new function with an automated process incorporated in the MID-NET® and was repeated periodically to examine trend changes of the HRs with multiple time points during the study period from January 1, 2016 to December 31, 2023.

Results: The number of patients varied according to the outcome, but there were approximately 600–1000, 50–100, and 1000–2000 patients for tix/cil, cas/imd, and peramivir, respectively. Some typical patterns were found when the analysis was repeated, although various patterns of changes over time were observed. For example, the aHR for hyperkalemia (CTCAE grade 2) as compared with cas/imd was higher than 1.0 initially but gradually approached 1.0 with a stable point estimate in the later period (0.92 (0.12-7.34)). On the other hand, the aHR for thrombocytopenia (CTCAE grade 3) as compared with that of peramivir showed significantly higher aHR at the beginning and continued to maintain a higher aHR even at the end of the study period (2.34 (1.18-4.64)).

Conclusions: Safety signal of an anti-COVID-19 drug (tix/cil) could be monitored by using the function of the MID-NET® in more timely manner. The practical use of this function could enhance the understanding of drug safety profiles at the early stage after its approval and contribute to the improvement of post-marketing safety measures.