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Objective

To evaluate changes in bone turnover and bone mineral density (BMD) in subjects with rheumatoid arthritis (RA) on glucocorticoid (GC) after discontinuing denosumab for 12 months.

Methods

Randomized, double-blind, placebo-controlled phase 2 study of subjects with RA. Subjects received placebo, or denosumab 60 or 180 mg every 6 months for 12 months and were followed for an additional 12 months after discontinuation, during which no bone loss prevention therapy was instituted. Changes from baseline in serum C-terminal telopeptide of type I collagen (CTX), procollagen type I N-terminal propeptide (P1NP), and lumbar spine (LS) and total hip (TH) BMD were evaluated.

Results

In this post-hoc analysis of subjects treated with GCs at study baseline (N = 82). CTX and P1NP decreased significantly from baseline in both denosumab groups. Following denosumab discontinuation, CTX returned to baseline and was not significantly different from placebo 6 and 12 months after discontinuation. Median percent changes from baseline P1NP with denosumab 60 mg were -0.16% and 15.3% at 6 and 12 months, respectively, after discontinuation (P=0.062 and 0.017 vs placebo); corresponding changes with denosumab 180 mg were 9.0% and 75.8% (P=0.018 and 0.002). Compared with placebo, LS and TH BMD increased in subjects receiving denosumab, and returned to baseline 12 months after discontinuation. No osteoporotic fractures were reported during the treatment or off-treatment periods.

Conclusion

In this analysis of short-term denosumab use in subjects with RA receiving GCs, denosumab discontinuation resulted in a gradual increase in bone turnover, which was associated with a return to baseline LS and TH BMD.

Read a Q&A of study highlights here.