麻豆传媒

Discontinuing denosumab (Prolia, Xgeva) was associated with a return to baseline bone mineral densities (BMD) in both the hip and lumbar spine.

That's according to findings published in .

The randomized, double-blind, placebo-controlled phase 2 study ultimately included 82 subjects with RA who were receiving glucocorticoids (GC). Of these, 26 received placebo, 27 received 60 milligrams of denosumab, and 29 received 180 milligrams of denosumab every 6 months for 12 months, followed by a 12-month follow-up after discontinuation.

Compared with placebo, lumbar spine and total hip BMD increased in subjects receiving denosumab, but BMD returned to baseline levels 12 months after discontinuation. Levels of serum C-terminal telopeptide of type I collage (CTX) and procollagen type I N-terminal propeptide (P1NP) were reduced during treatment compared with baseline levels and placebo, but returned to pretreatment levels following discontinuation of denosumab.

The study was led by Kenneth Saag, MD, MSc, a rheumatologist-researcher with the University of Alabama at Birmingham; coauthors included investigators with Amgen, which developed the drug. The following highlights are culled from the study and have been edited for length and clarity.

What was the specific knowledge gap this study was designed to address, and why was this the right juncture to address it?

Bone loss in people with RA can be exacerbated by glucocorticoids, which in turn leads to a higher risk of fractures. Denosumab is approved for the treatment of GC-induced osteoporosis in the U.S and elsewhere.

Previous studies have shown that discontinuing denosumab led to a transient increase in bone turnover markers above baseline. This is associated with a reduction in BMD and an increased risk of vertebral fractures -- particularly multiple vertebral fractures. Therefore, a need existed to better understand the effects of denosumab discontinuation, including bone turnover and BMD responses, in patients with RA receiving GC therapy.

What were the key findings?

The results indicated that discontinuation of denosumab after 1 year of treatment with 60 or 180 milligrams every 6 months resulted in the reversal of its inhibitory effect on bone turnover markers and BMD gains.

Further, serum CTX returned to pretreatment levels and P1NP slightly above baseline 12 months after the last denosumab dose. On-treatment lumbar spine and total hip BMD gains decreased to pretreatment levels 18 months after the last dose.

What were the study's limitations?

The relatively small sample size was a limitation, according to the authors, as was the fact that the post-hoc analysis arose from a study not specifically designed to assess denosumab discontinuation.

Participation in the follow-up extension period was not mandated, and the lack of bone-sparing therapy may have led to many patients choosing not to continue beyond the 12-month study period. Fluctuations in the use of GC within subjects, which could have had an impact on fracture risk, also were not captured in the study.

What are the potential implications of these findings for rheumatology practices?

The present data highlight a need for follow-on osteoporosis therapy in people with RA to preserve BMD gains in patients who discontinue denosumab.

This study was not designed to identify effective follow-on therapies that are best positioned to address BMD reductions after denosumab discontinuation. However, previous evidence has shown that bisphosphonates could reduce bone loss to varying degrees in postmenopausal women with osteoporosis who discontinue denosumab.

Read the study here.