麻豆传媒

ORLANDO -- Two studies reported here detailed strategies for switching patients from denosumab (Prolia) to alternative bisphosphonates while keeping markers of bone health in the desired range.

In one, researchers showed that most patients were able to transition smoothly to oral alendronate (Fosamax) without significant loss of bone mineral density (BMD); the other obtained similar results with patients switched to zoledronic acid (Reclast).

Both were presented at the American Society for Bone and Mineral Research's 2019 annual meeting.

Although no maximum duration of therapy has been set for denosumab, patients developing adverse effects, or needing to stop it for other reasons, are generally advised to switch to another antiresorptive medication. Previous studies have shown that BMD declines rapidly and fracture risk soars when denosumab is withdrawn. But there is limited data on patients transitioning from denosumab to other agents such as bisphosphonates.

In the first presentation, David Kendler, MD, of the University of British Columbia, reported on data from the Denosumab Adherence Preference Satisfaction (DAPS) Study in which patients received one year of denosumab therapy followed by one year of alendronate.

The DAPS study examined adherence, preference, and satisfaction to see whether patients adhered more to monthly doses or weekly doses of alendronate with additional parameters of preference and satisfaction. The study measured BMD at baseline, 12, and 24 months as well as an evaluation of patient characteristics.

Subjects in the DAPS study were all postmenopausal women over the age of 55 with bone densities from 2 to 4 standard deviations below normal for total hip, spine, or femoral neck.

About 90% completed the denosumab treatment and some 83% completed the second year of alendronate treatment.

Treatment resulted in a marked decline in bone turnover markers during the denosumab phase, which were more or less maintained during the alendronate year. Denosumab treatment resulted in a 5%-6% mean increase in spine BMD, 3.2% increase in total hip BMD, and 3.1% in femoral neck BMD, which did not change substantially after switching to alendronate.

Analysis of gainers, maintainers, and losers indicated that approximately 80% gained or maintained bone density after a year of alendronate therapy with about 16% losing spine bone density, 21% losing femoral neck density, and 7.6% losing total hip density.

Adherence was considered high during both and there were not significant differences in adherence rate in the second year.

Kendler and colleagues concluded that switching to alendronate after denosumab was generally effective at maintaining increases in BMD.

In the second presentation, Joy Tsai, of Massachusetts General Hospital in Boston, presented data from an extension phase in the DATA-HD clinical trial, .

In the main study, women age 45 and above were randomized to one of two groups: either 20 or 40 micrograms of teriparatide (Forteo) taken daily over 9 months. This was overlapped by treatment with 60 micrograms of denosumab given subcutaneously every 6 months from 3 to 15.

Similar to the first phase of Kendler's study, this regimen led to substantial increases in BMD. Then, at month 15, all participants were invited to switch to zoledronic acid, as long as they did not have contraindications such as renal impairment. Zoledronic acid was administered as a single 5-mg infusion.

A total of 53 patients participated in the extension, about equally divided between those who had been on the low and high doses of teriparatide.

At baseline, the average was age 66 with roughly half having had a previous fragility fracture and/or prior bisphosphonate use. The average duration of use was 4.7 years, which was stopped a mean of about 6 years prior to enrollment.

Again, as in the alendronate study, patients in the DATA-HD extension generally maintained the BMD gains they'd obtained with denosumab and teriparatide. Only two individuals exhibited decreased total BMD after the zoledronic acid infusion, and two minor vertebral fractures were reported.

One potentially instructive result was that patients who received zoledronic acid less than 26 weeks from the last denosumab dose experienced greater decreases in femoral neck and total hip bone density than those who received the infusion 26 to 36 weeks after the last denosumab injection.