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Since its approval for patients with multiple myeloma in early 2018, uptake of denosumab (Xgeva) has been rapid, with a new study reporting the drug now reaching almost 40% of the bone-modifying market for this disease.

Of 15,782 patients with multiple myeloma who had at least one dose of a bone-modifying agent taken from Medicare fee-for-service claims, the rate of denosumab use was 3.8 doses per 1,000 person-months in the year prior to the FDA approval compared with 84.1 doses per 1,000 person-months in the 15-month period after its approval, reported Arjun Gupta, MD, of Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, and colleagues .

Prior to approval, denosumab accounted for only 0.1% of the total number of bone-modifying agent doses. After its approval, that increased to 38.1%.

In the (also known as the ) underpinning denosumab's approval for the multiple myeloma indication, the drug was non-inferior to zoledronic acid (Zometa) for time to first skeletal-related event (SRE) and resulted in greater preservation of renal function compared with standard-of-care zoledronic acid.

"Patients with kidney dysfunction could benefit from denosumab over bisphosphonates given this lower risk," Gupta told MedPageToday.

However, the data reported by Gupta and colleagues showed that the incidence rate ratio of postapproval use of denosumab was more than double in patients without renal dysfunction compared with patients with renal dysfunction.

Gupta acknowledged that the study did not examine reasons for this rapid uptake on denosumab, but he offered a few possible explanations.

First, physicians may not be aware that the approval of denosumab in myeloma was based on a non-inferiority trial instead of a superiority trial.

"When there is a new drug approved, people may be more likely to use it because often 'new' is confused with 'better,'" Gupta said.

A second possible explanation for denosumab's increased use is its subcutaneous administration compared with the intravenous administration of zoledronic acid.

"This efficiency could be contributing to [uptake]," Gupta said. "The trouble with this is that many patients with myeloma now get IV therapies anyway. The patients are often sitting there for two hours anyway."

Third, it is possible that reimbursement for denosumab is somehow incentivizing physicians to use the more costly drug, Gupta said. Denosumab is estimated to cost about $24,000 more per patient per year than zoledronic acid.

In an e-mail, Gupta explained that certain drugs and other products administered in the physician office setting are covered by Medicare Part B. Medicare pays for the drug cost, with an additional 6% of the "average sales price" as calculated by the government, to cover for overhead and variable acquisition costs. With the higher list price, the 6% add-on also goes higher and therefore may serve as an incentive to physicians to use it over cheaper drugs.

Finally, Gupta noted that physicians could also be taking into account a published (but unplanned and post hoc) analysis of progression-free survival in the '482 trial that showed an almost 11-month progression-free survival benefit for denosumab compared with zoledronic acid.

"Many thought leaders in the field don't think these data are completely accurate though," Gupta said. "I am not sure we should be basing drug decisions on this exploratory analysis."

Gupta emphasized that these data are not meant to imply that denosumab is a bad drug.

"There are many patients who have done well on denosumab and really need it," Gupta said. "But we wanted to point out that just because we have a new drug approval, we should not all switch to it."

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