Romosozumab FDA Label May Have Reduced Cardiovascular Risks in Osteoporosis Patients


Interim data from a post-marketing analysis suggest a boxed label warning for the drug in 2019 may have limited high-risk patients taking the biologic therapy.

Romosozumab FDA Label May Have Reduced Cardiovascular Risks in Osteoporosis Patients

Post-menopausal osteoporosis medication romosozumab (Evenity) was not associated with a notably high prevalence of myocardial infarction (MI) or stroke in the first year of treatment for eligible patients, according to findings from a post-marketing US Food and Drug Administration (FDA)-required safety assessment.

The findings, presented at the American College of Rheumatology (ACR) 2021 Convergence this week, suggest the boxed warning label which accompanied the FDA’s 2019 approval for romosozumab may have helped limit the prevalence of cardiovascular outcomes in women taking romosozumab for post-menopausal osteoporosis.

The FDA originally approved romosozumab as a once-monthly injection therapy for osteoporosis in postmenopausal women with a high risk of bone fracture in April 2019. The packaging included a boxed warning on its label for the drug’s increase of heart attack, stroke, and cardiovascular deaths, and patients who have suffered such an event in the past year were advised to not take the therapy.

Investigators, led by Jay Lin, PhD, Pharmacoepidemiologist for Amgen, presented results from the ongoing assessment of the impact of the romosozumab boxed warning, as well as the feasibility of future comparative safety analysis in real-world data. As they noted, approximately 15,000 person-years of romosozumab exposure had been reported in the US as of March 2021. Their interim report covered Optum claims and supplemental electronic health record data from April 2019 to March 2020.

The retrospective, repeated analysis was conducted within 5 single-year blocks of calendar time following the FDA approval of romosozumab in April 2019. Lin and colleagues included women ≥55 years old on newly-initiated romosozumab, denosumab, zolendronate, PTH analogues, or oral bisphosphonates in the assessment.

The investigators sought to describe the proportion of women to experience MI or stroke in the year prior to initiating osteoporosis treatment, as well as their history of cardiovascular disease and other comorbidities and concomitant medications. Their historical data spanned up to 19 years of patient clinical information.

Lin and colleagues conducted 4 pairwise comparisons to describe differences in patient clinical histories compared with romosozumab, before and after propensity score matching.

They found that patients initiating romosozumab (n = 1946) were generally older (mean age, 74.8 years) than patients on zolendronate (n = 6292; 72.9), PTH analogues (n = 1517; 70.7) and oral bisphosphonates (n = 38,544; 72.1). Romosozumab patients reported increased prevalence of chronic diseases including hypertension, hyperlipidemia, and type 2 diabetes.

Patients initiating the regulated therapy were also more likely to frequently use health care and report more osteoporosis treatment use and prior fractures. Romosozumab patients more likely to have a history of MI (9%) or stroke (11.5%) than patients on denosumab (6.8%; 8.6%), PTH analogues (7.4%; 9.0%), zolendronate (5.9%; 7.0%) and oral bisphosphonates (5.4%; 6.0%).

However, the proportion of patients to have an MI or stroke in the 1 year prior to taking romosozumab was just 0.4% and 0.5%, respectively—a rate similar to other therapies for osteoporosis.

Lin and colleagues concluded that the FDA’s regulation of the recently-approved osteoporosis therapy—and the warnings included with it—may have mitigated the prevalence of cardiovascular risks in its early patient population.

“Patients who initiated romosozumab were a high osteoporosis-risk population and generally had more comorbidities including cardiovascular risk factors,” they wrote. “Nevertheless, the low proportion of patients who had a MI/stroke within 1 year prior to treatment initiation suggests the label boxed warning language may have had the intended effect on patient selection.”

The study, ”Clinical Characteristics, Including History of Myocardial Infarction and Stroke, Among US PMO Women Initiating Treatment with Romosozumab and Other Anti-osteoporosis Therapies,” was presented at ACR 2021.

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