Cardiovascular Safety Profile of Romosozumab: A Pharmacovigilance Analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS).
Annika Vestergaard KvistJunaid FaruqueEnriqueta Vallejo-YagüeStefan WeilerElizabeth M WinterAndrea Michelle BurdenPublished in: Journal of clinical medicine (2021)
Background: Cardiovascular safety concerns for major cardiovascular events (MACE) were raised during the clinical trials of romosozumab. We aimed to evaluate the cardiovascular safety profile of romosozumab in a large pharmacovigilance database. Methods: All cases reported between January 2019 and December 2020 where romosozumab was reported were extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS). The outcome of interest was MACE (myocardial infarction (MI), stroke, or cardiovascular death). A disproportionality analysis was conducted by estimating the reporting odds ratios (RORs) and 95% confidence intervals. Disproportionality analyses were stratified by sex and reporting region (US, Japan, other). Results: Of the 1995 eligible cases with romosozumab, the majority (N = 1188; 59.5%) originated from Japan. Overall, 206 suspected MACE reports were identified, of which the majority (n = 164; 13.8%) were from Japan, and 41 (5.2%) were from the United States (US). Among Japanese reports, patients were older and more frequently male than reports from the US. Similarly, cases with a reported MACE were older and had higher reports of cardioprotective drugs than those without cardiovascular events. Elevated reports for MACE (ROR 4.07, 95% CI: 2.39-6.93) was identified overall, which was primarily driven by the significant disproportionality measures in the Japanese reports. Conclusions: The current pharmacovigilance study identified a potential signal for elevated MACE, particularly in Japan. The results support the current safety warnings from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to avoid use in high-risk patients.
Keyphrases
- adverse drug
- drug administration
- cardiovascular events
- electronic health record
- end stage renal disease
- emergency department
- coronary artery disease
- clinical trial
- cardiovascular disease
- drug induced
- ejection fraction
- prognostic factors
- newly diagnosed
- chronic kidney disease
- randomized controlled trial
- peritoneal dialysis
- pulmonary embolism
- left ventricular
- physical activity
- type diabetes
- patient reported outcomes
- climate change
- risk assessment
- phase ii