A second course of romosozumab led to either gains in or maintenance of bone mineral density (BMD) in postmenopausal women who were 12 months off treatment or transitioning from denosumab, according to study results published in Osteoporosis International.
The researchers reported findings from an extension of the phase 2 dose-finding study of romosozumab, which compromised postmenopausal women between 55 and 85 years of age with low bone mass (T-score ≤-2.0 and ≥-3.5 at the femoral neck, lumbar spine, or total hip). Patients received romosozumab or placebo during months 0 to 24, followed by placebo or denosumab during the extension period (months 24-36). To investigate the efficacy and safety of a second course of romosozumab, all patients were then switched from placebo or denosumab to monthly romosozumab 210 mg (month 36-48).
Of 167 participants who entered the second-dose period, 35 were randomly assigned to initially receive romosozumab. Of this group, patients who received placebo in months 24 to 36 (n=19) saw increased BMD by amounts comparable to those seen from months 0 to 12 at the total hip (6.0% vs 5.5%, respectively), lumbar spine (12.4% vs 12.0%, respectively), and femoral neck (6.3% vs 5.4%) after the second romosozumab course. Among patients prescribed denosumab in months 24 to 36 (n=16), a second course of romosozumab increased BMD at the lumbar spine (2.3%), which counteracted the expected BMD loss after denosumab discontinuation. For these patients, BMD was maintained at the total hip and femoral neck.
The second course of romosozumab was generally well tolerated, with similar rates of adverse events as the first course of romosozumab (80.0% vs 84.3%, respectively). Notable adverse events included hypersensitivity, injection-site reactions, malignancy, and osteoarthritis.
The study was limited by the small sample size, which was too small to examine change in fracture risk.
“Since all currently available osteoporosis therapies are reversible over variable time frames, off-treatment patient response must be understood to properly sequence treatments to manage osteoporosis as a chronic disease,” investigators wrote. “The effect of a second course of romosozumab provides needed data to inform possible long-term therapeutic decisions in those patients who remain at high risk for fracture.”
Disclosure: Funding for this study was provided by Amgen Inc., Astellas, and UCB Pharma. Multiple authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Kendler DL, Bone HG, Massari F, et al. Bone mineral density gains with a second 12-month course of romosozumab therapy following placebo or denosumab [published online October 18, 2019]. Osteoporos Int. doi:10.1007/s00198-019-05146-9