Safety and Efficacy of Romosozumab Demonstrated in Postmenopausal Women With Mild to Moderate CKD

The safety and efficacy of romosozumab for osteoporosis treatment in postmenopausal women are not significantly affected by reduced kidney function, according to study results presented at the European League Against Rheumatism (EULAR) 2020 E-Congress, held online from June 3 to 6, 2020.

Osteoporosis treatment options are needed for patients with renal insufficiency. In a post hoc analysis of the ARCH (ClinicalTrials.gov Identifier: NCT01631214) and FRAME (ClinicalTrials.gov Identifier: NCT01575834) clinical trials, investigators aimed to determine whether baseline kidney function affects the safety and efficacy of romosozumab in postmenopausal women.

Between the 2 trials, more than 11,000 women were randomly assigned 1:1 to receive either romosozumab (210 mg/mo) or a comparison treatment (alendronate 70 mg/wk or monthly placebo) for 12 months. Patients were grouped by baseline estimated glomerular filtration rate (eGFR), with normal kidney function defined as eGFR ≥90 mL/min/1.73 m², mild insufficiency as eGFR 60 to 89 mL/min/1.73 m², and moderate insufficiency as eGFR 30 to 59 mL/min/1.73 m².

Outcomes of interest included least squares mean percent change in bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck; the incidence of new vertebral fractures and adverse events; and changes in kidney function at 12 months.

The majority of patients in both trials (84%-88%) had mild or moderate renal insufficiency.

In both trials, the change from baseline in BMD was significantly higher in the romosozumab group across all baseline eGFR categories. There was a significant interaction between kidney function and BMD increase at the lumbar spine and total hip associated with romosozumab use, such that BMD gains in women with impaired kidney function were lower than in those with normal function. However, differences in BMD gains between the romosozumab and comparison groups were still significant among women with impaired kidney function.

In the ARCH trial, the incidence of new vertebral fractures at 12 months was similar across all kidney function groups (3.2%-3.4%). Similar results were seen in the FRAME trial (0.4%-0.6%). In both trials, the incidence of new vertebral fracture was lower in the treatment group than the comparison groups.

The incidences of adverse events and serious adverse events were similar in the romosozumab and comparison groups both within and across eGFR groups. Mild to moderate hypocalcemia occurred in 3 women between both trials. In total, 24 women had decreases in serum calcium levels that were considered mild or moderate in all romosozumab-treated patients.

A similar percentage of women in each trial had changes in kidney function over 12 months.

“The efficacy and safety of romosozumab vs alendronate or placebo was similar among postmenopausal women with osteoporosis and different levels of [kidney] function,” the researchers concluded.

Disclosures: This study was supported by Amgen, Astellas, and UCB Pharma. Several authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.

Reference

Miller P, Adachi J, Albergaria BH, et al. Efficacy and safety of romosozumab among postmenopausal women with osteoporosis and mild-to-moderate chronic kidney disease. Presented at: EULAR 2020 E-Congress; June 3-6, 2020. Abstract OP0297.