January 07, 2020
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Delays between denosumab injections may worsen BMD response

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Houchen Lyu

A longer interval between denosumab injections is associated with suboptimal bone mineral density response at the spine and total hip, and strategies to improve the timely administration of denosumab in real-world settings are needed, according to findings published in The Journal of Clinical Endocrinology & Metabolism.

“In a study led by Daniel H. Solomon, MD, MPH, from Brigham and Women’s Hospital, the researchers found long-term adherence of denosumab was suboptimal,” Houchen Lyu, MD, PhD, a research fellow in the section of clinical sciences, division of rheumatology at Brigham and Women’s Hospital, told Healio. “Patients with good adherence had an average BMD increase of 3.9% at the lumbar spine, higher than patients with moderate (3%) or poor adherence (1.4%). Similar association was found for BMD at the total hip.”

Daniel H. Solomon

Lyu and colleagues analyzed electronic medical records data from 151 adults aged at least 45 years identified as new users of denosumab (Prolia, Amgen) who received at least two 60 mg doses between October 2010 and December 2017 (938 injections; mean age, 69 years; 95% women). Denosumab adherence was evaluated by the medication coverage ratio (MCR), which measures the percentage of days a person was covered therapeutically during a given time interval after receiving denosumab.

“The MCR was calculated based on the assumption that each injection of denosumab provides 180 days of therapeutic coverage and the effect of denosumab wanes after this period,” the researchers wrote.

Researchers defined good adherence as a dosing interval of 7 months or shorter (defined by MCR 93%); moderate adherence as a dosing interval of 7 to 10 months (MCR 75%-93%); and poor adherence was defined as a dosing interval at least 10 months (MCR 74%). Primary outcomes were annualized percent BMD changes from baseline at the lumbar spine, total hip and femoral neck.

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A longer interval between denosumab injections is associated with suboptimal bone mineral density response at the spine and total hip, and strategies to improve the timely administration of denosumab in real-world settings are needed.

Within the cohort, adults received an average of six doses of denosumab, with 15% receiving two to three doses, 62% receiving four to eight doses, and 23% receiving more than eight doses. Mean follow-up time was 37 months.

Overall, 21% of administered denosumab injections were delayed by more than 1 month. Nearly all adults received their second injection within 10 months of the first dose; however, only 40% of patients received a dose within the same time frame after their 10th injection, suggesting that 60% of adults would have at least one injection delayed for more than 4 months at year 5, according to the researchers.

Researchers found that adults with good adherence experienced an annualized BMD increase of 3.9% at the lumbar spine compared with those with moderate (3%) or poor adherence (1.4%; P = .002), with results persisting after adjustment for age, sex, BMI, fracture history, bisphosphonate history and duration and number of previous denosumab injections. Similarly, adults with good adherence experienced an annualized BMD increase of 2.1% at the total hip compared with those with moderate (1.3%) or poor adherence (0.6%; P = .002).

“These results highlight the importance of timely denosumab administration when using this drug for long-term osteoporosis management,” Lyu said. “Strategies to improve timely administration of denosumab in the real-world setting are needed.”

Lyu said the findings suggest that a delay in denosumab administration of more than 4 months may be “unacceptable”; however, future studies are needed to determine the exact threshold.

“Also, future studies with fracture as an endpoint are needed to provide a conclusive answer as to whether this difference in BMD response among different groups predicts an increase in fracture risk,” Lyu said. – by Regina Schaffer

For more information:

Houchen Lyu, MD, PhD, can be reached at the Division of Rheumatology, Brigham and Women’s Hospital, 60 Fernwood Road, Boston, MA 02115; email: hlyu1@bwh.harvard.edu.

Disclosure: One of the study authors reports he receives salary support from research grants unrelated to osteoporosis from Amgen.