Verification of efficacy and safety of ibandronate or denosumab for postmenopausal osteoporosis after 12-month treatment with romosozumab as sequential therapy: The prospective VICTOR study.

Abstract

Romosozumab is a potent drug for treating postmenopausal osteoporosis but has a limited dosing period of 12months. Bone mineral density (BMD) decreases soon after romosozumab discontinuation, thus emphasizing the importance of appropriate sequential treatment. The present VICTOR randomized controlled study compared the efficacy of ibandronate and denosumab as sequential therapy options following 12-month romosozumab treatment. Subjects completing 12months of romosozumab administration for severe postmenopausal osteoporosis were randomly assigned to receive either ibandronate or denosumab for an additional 12months. The primary outcome of interest was the percentage changes in BMD at the lumbar spine, total hip, and femoral neck from 12months (completion of romosozumab) to 18 and 24months of total treatment (6 and 12months, respectively, after the conversion to sequential therapy). Secondary outcomes included alterations in serum bone turnover markers and the incidence of adverse events. Sixty-two subjects each in the ibandronate and denosumab groups completed the sequential therapy. The respective percentage changes in BMD at the lumbar spine from 12months to 24months were 2.5% in the ibandronate group and 5.4% in the denosumab group. At 24months, we observed significant differences versus 12months for both groups as well as between the groups (all P<0.01), showing a superior ability to increase BMD at the lumbar spine for denosumab over ibandronate. BMD gains at the total hip and femoral neck exhibited comparably favorable trends. P1NP and TRACP-5b were significantly decreased from 12 to 24months (-64.9% and-26.8% in the ibandronate group and-67.4% and-36.3% in the denosumab group, respectively; all P<0.001 versus 12months). Several minor adverse events were recorded in both groups, none of which led to the discontinuation of the trial. The VICTOR study revealed that denosumab could be considered more effective than ibandronate, with few severe adverse events, for the enhancement of BMD as a sequential agent after romosozumab in postmenopausal osteoporosis patients.