(P-381) Cardiovascular Safety Profile of Romosozumab: A Pharmacovigilance Analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS)

Background: Romosozumab is a new monoclonal antibody for the treatment of osteoporosis. Cardiovascular safety concerns for major cardiovascular events (MACE) were raised during the clinical trials resulting in safety warnings for contraindication in those with previous cardiovascular events or risk factors being issued by the US Food and Drug Administration (FDA) and the European Medicines Association (EMA). The Japanese authorities have not issued a safety warning regarding cardiovascular risk.

Objectives: To evaluate the cardiovascular safety profile of romosozumab in a large pharmacovigilance database.

Methods: All cases reported between 01-01-2019 and 31-12-2020 where romosozumab was reported were extracted from the FDA Adverse Event Reporting System (FAERS) public quarterly files. The primary outcome of interest was MACE (myocardial infarction [MI], stroke, or cardiovascular death). Case characteristics, including co-reported cardiovascular medications, were identified, and differences between cases with a reported MACE were assessed. A disproportionality analysis was conducted by estimating the reporting odds ratios (RORs) and 95% confidence intervals. Disproportionality analyses were stratified by sex and region of report. A secondary analysis examined other cardiovascular events.

Results: Of the 1,995 eligible cases with romosozumab, 75% were female and the mean age was 76.7 years. There were 206 (8.8%) cases with a reported MACE, including 86 (4.3%) with cardiovascular death, 84 (4.2%) with stroke, and 42 (2.1%) with MI. Cases with a reported MACE were older than those without any cardiovascular events reported (mean age 81.2 vs 76.4 years, respectively, p<0.05) and had higher reporting of cardiovascular drugs. The disproportionality analysis identified elevated reporting for MACE (ROR 4.07, 95% CI: 2.39–6.93), including all individual events: MI (ROR 3.1, 95% CI 1.43–6.72), stroke (ROR 3.47, 95% CI 1.81–6.69), and cardiovascular death (ROR 4.90, 95% CI 2.55–9.40). The highest estimates of disproportionality were observed among males and in reports originating from Japan. No evidence of elevated reporting was observed for other cardiovascular events.

Conclusions: The current pharmacovigilance study identified a potential signal for elevated reporting of MACE, particularly in Japan. The results support the current safety warnings from the FDA and EMA to avoid use in high-risk patients.