ORLANDO – Use of romosozumab (Evenity) by patients with osteoporosis in various stages of renal insufficiency did not appear to affect increases in bone mineral density, the rate of new vertebral fractures, or the number of adverse events when compared with placebo, Paul D. Miller, MD, said at the annual meeting of the American Society for Bone and Mineral Research.
“Romosozumab could be considered a treatment option for osteoporotic patients with mild to moderate reductions in renal function,” said Dr. Miller, distinguished clinical professor of medicine at the University of Colorado at Denver, Aurora.
Since bisphosphonates are not recommended for use in patients with an estimated glomerular filtration rate (eGFR) of less than 30 or 35 mL/min/1.73 m2, other osteoporosis treatments such as romosozumab should also be examined. “It is important to evaluate other osteoporosis treatments in this setting, particularly in the context of monoclonal antibodies, which are not cleared in the kidneys and are metabolized in the reticular endothelial system, and have no FDA ... cut-off for their use,” Dr. Miller said.
Dr. Miller and colleagues performed a post hoc analysis of patients in the FRAME study, which enrolled 3,589 patients who received a monthly dose of subcutaneous romosozumab (215 mg) and 3,591 patients who received placebo in a double-blinded study for 12 months before moving to a 12-month, open-label portion of the study where all patients received 60 mg of subcutaneous denosumab every 6 months. After 12 months, the researchers analyzed the least squares mean (LSM) percentage change in bone mineral density (BMD) at the total hip, lumbar spine, and femoral neck as well as whether patients had any new vertebral fractures or experienced adverse events from treatment.
Patients were postmenopausal women between ages 55 and 90 years with a BMD T-score between –2.5 and –3.5 at the total hip or femoral neck. Researchers divided patients into four eGFR groups based chronic kidney disease (CKD) stage: normal (90 mL/min/1.73 m2 or higher; 848 patients), mild CKD (60-89 mL/min/1.73 m2; 4,939 patients), moderate CKD (30-59 mL/min/1.73 m2; 1,360 patients), and severe (15-29 mL/min/1.73 m2; 18 patients).
The LSM percentage change was 13.1% in the lumbar spine (95% confidence interval, 12.8%-13.3%) for the romosozumab group, compared with 0.4% in the placebo group (95% CI, 0.2%-0.5%). The LSM percentage change for total hip was 6.0% in the romosozumab group (95% CI, 5.9%-6.2%), compared with 0.3% in the placebo group (95% CI, 0.1%-0.4%), while the LSM percentage change for the femoral neck was 5.5% in the romosozumab group (95% CI, 5.2%-5.7%) and 0.3% in the placebo group (0.1%-0.5%).
“[The] risk of new vertebral fractures was decreased in all eGFR subgroups and did not appear to be affected by eGFR level,” he said.
Specifically, vertebral fracture incidence was 0.5% in the romosozumab group, compared with 3.0% in the placebo group, for patients with normal renal function, 0.4% in the romosozumab group, compared with 1.5% in the placebo group, for patients with mild chronic kidney disease, and 0.6% in the romosozumab group vs. 2.1% in the placebo group for patients with moderate chronic kidney disease. The incidence of adverse events, serious adverse events, and positively adjudicated cardiovascular events were similar between patients in the romosozumab group regardless of renal function status. The researchers reported 1 patient in the romosozumab group who experienced grade 2 hypocalcemia, and 14 patients in the romosozumab group who experienced mild to moderate decreases in calcium, compared with 4 patients in the placebo group.
Dr. Miller noted the study was limited by having few patients with an eGFR of less than 30 mL/min/1.73 m2 and no patients with an eGFR of less than 15 mL/min/1.73 m2, but said the study strengths were its large randomized nature and well-balanced baseline characteristics between each group.
This study was sponsored in part by Amgen, Astellas, and UCB Pharma. Dr. Miller reported receiving grants from Alexion, Amgen, Radius, Regeneron, UCB, and Ultragenyx. Amgen and UCB assisted in and provided financial assistance for the preparation of Dr. Miller’s presentation.
SOURCE: Miller P et al. ASBMR 2019.