Treatment sequence influences romosozumab effectiveness in osteoporosis
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Women with osteoporosis who received romosozumab experienced the greatest gains in bone formation when the drug was administered before antiresorptive therapy, according to a speaker.
“When you give romosozumab to previously untreated women, bone formation increases and bone resorption decreases, consistent with the dual effect of this agent,” Felicia Cosman, MD, professor of medicine at Columbia University College of Physicians and Surgeons and co-editor-in-chief of Osteoporosis International, told Healio. “Bone mineral density gains are greatest from romosozumab when given to previously untreated women. When you give romosozumab to people who have been prescribed alendronate or denosumab, the BMD gains are lower compared to the previously untreated woman. However, when romosozumab is given after alendronate, BMD increments in both total hip and spine are significant and substantial. When romosozumab is given after denosumab, BMD increases in the spine and is maintained in the total hip. In both cases, these BMD results are superior to the BMD effect of switching to teriparatide.”
Cosman presented the findings at the American Society for Bone and Mineral Research virtual meeting.
Cosman and colleagues analyzed data from four trials in which romosozumab-aqqg (Evenity, Amgen) was administered. In the phase 3 ARCH trial and phase 3 FRAME trial, participants received romosozumab before a switch to antiresorptive therapy. In the phase 3 STRUCTURE trial and a phase 2 trial, romosozumab was administered after participants received antiresorptive treatment with alendronate or denosumab, respectively. Researchers analyzed biochemical markers of bone turnover, as well as total hip and spine BMD change across all four studies after 1 year of romosozumab treatment and the 2-year, cumulative change after sequential treatment with romosozumab and an antiresorptive.
Data from the ARCH trial showed the largest BMD gains after 1 year of romosozumab, with a mean total hip BMD gain of 6.2% and mean spine BMD gain of 13.7%. Data from the FRAME trial showed similar mean BMD gains of 6% at the total hip and 13.1% at the spine. In the STRUCTURE trial, in which romosozumab was administered after alendronate, mean 1-year BMD gains were 2.9% at the total hip and 9.8% at the lumbar spine. The phase 2 trial in which denosumab (Prolia, Amgen) was administered before romosozumab showed the lowest mean 1-year BMD gains at 0.9% at the total hip and 5.3% at the lumbar spine.
Analysis of 2-year cumulative gains showed the FRAME study, which administered romosozumab followed by denosumab to participants, had the largest mean gains with an 8.5% increase in total hip BMD and a 16.6% spine BMD increase. The ARCH study, which administered romosozumab followed by alendronate, reported a mean total hip BMD increase of 7.1% and a mean spine BMD increase of 15.2% after 2 years. Mean 2-year gains in the phase 2 study, in which denosumab was followed by romosozumab, were lower at 3.8% in total hip BMD and 11.5% in spine BMD.
“With denosumab first, there is still a lot of bone gain when romosozumab is initiated,” Cosman said. “However, there is also a great deal of breakdown, largely due to denosumab withdrawal. We always need to consider the effects on both formation and resorption to determine the ultimate effect on BMD.”
Cosman said the findings supported the initial use of an anabolic treatment in individuals with osteoporosis at high risk for fracture, particularly those at high imminent risk, rather than starting with an antiresorptive. This data confirmed the findings from earlier studies that showed treatment with teriparatide (Forteo, Eli Lilly; Bonsity, Alvogen) followed by an antiresorptive led to greater bone formation than the reverse sequence.
“When we identify very high-risk patients, especially those with new fractures or a history of multiple fractures, or very low BMD with clinical risk factors, we should think about using anabolic treatment first, rather than starting with an antiresorptive and then using an anabolic down the line,” Cosman said. “We now show this to be true with romosozumab in addition to teriparatide. BMD gains are better and the anti-fracture efficacy is clear in the setting of ‘anabolic first.’ Slowly, guidelines and reimbursement patterns are heading in this direction.”
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Cosman F, et al. Treatment sequences with romosozumab before or after antiresorptive medication. Presented at: American Society for Bone and Mineral Research Annual Meeting; Sept. 11-15, 2020 (virtual meeting).
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