Cardiovascular Risk of Romosozumab vs. Teriparatide: A Cohort Study Using Japan's National Claims Database

Clin Pharmacol Ther. 2025 Nov 21. doi: 10.1002/cpt.70142. Online ahead of print.

ABSTRACT

Disproportionality analyses suggested a cardiovascular risk signal for romosozumab, while statistically significant associations were not found in the real-world database studies. Therefore, a larger comparative study was necessary to examine this signal. This study aimed to compare the cardiovascular risks of romosozumab with those of teriparatide in the overall population and in groups with a history of major adverse cardiovascular events (MACE). A new user cohort study was conducted using Japan's national claims database. Patients aged ≥ 40 years who initiated romosozumab or teriparatide between March 2019 and March 2023 were analyzed. A multivariable Cox proportional hazards model was used to estimate the adjusted hazard ratio (aHR) for MACE. Subgroup analyses were conducted based on MACE history. A total of 251,219 romosozumab and 500,445 teriparatide users were analyzed (most common age group was 80-89 years for both drugs; men: 9.33% for romosozumab and 14.14% for teriparatide). MACE occurred in 1853 romosozumab and 3427 teriparatide users, with incidence rates of 1.09 and 1.22 per 100 person-years, respectively. The aHR (95% confidence interval [CI]) for romosozumab compared with teriparatide was 1.00 (0.94-1.06). In subgroup analyses based on MACE history, the aHRs (95% CI) for no history, for the one-year period leading up to t₀, and for more than 1 year before t₀ were 1.01 (0.95-1.08), 0.93 (0.72-1.21), and 1.00 (0.85-1.18), respectively. In conclusion, no statistically significant difference in MACE risk was observed between romosozumab and teriparatide in Japan's national claims database, regardless of MACE history.

PMID:41272927 | DOI:10.1002/cpt.70142