Denosumab Discontinuation Reverses Its Effects on BMD in Patients with RA Treated with Glucocorticoids

Among patients with rheumatoid arthritis (RA) treated with glucocorticoids, discontinuation of denosumab (Prolia) after 12 months of therapy led to a reversal of its inhibitory effects on bone turnover markers and bone mineral density (BMD), according to results of a post-hoc analysis of a recent trial (Saag KG, et al. Arthritis Rheumatol. 2021 Sept 17. Epub ahead of print).

Kenneth G. Saag, MD, MSc, Jane Knight Lowe Endowed Chair, Division and Department of Medicine, University of Alabama at Birmingham, and American College of Rheumatology President, and colleagues conducted a post-hoc analysis of a subgroup of patients (N = 82) who were enrolled in a larger phase 2 trial of 218 individuals with RA. Participants in this trial had been randomized to receive placebo (N = 26), 60 mg denosumab (the approved dose, N = 27), or 180 mg denosumab (N = 29), given as 2 subcutaneous 6-month injections at baseline and 6 months, followed by 12 months without any bone-loss prevention therapy. The patients had a mean age of 55 years, and 62% were female.

The purpose of this analysis was to assess changes in the bone resorption marker, C-terminal telopeptide of type I collagen (CTX), and the bone formation marker, procollagen type I N-terminal propeptide (P1NP), as well as lumbar spine and total hip BMD following discontinuation of denosumab treatment.

Study Results

While receiving denosumab, patients’ serum levels of CTX and P1NP decreased significantly from baseline.

In patients who had received the 60-mg dose of denosumab, CTX levels had returned to baseline 6 months and 12 months after denosumab was discontinued. Median levels of P1NP in these patients were 0.16% lower than baseline and 15.3% higher than baseline at 6 months and 12 months, respectively, after denosumab was stopped.

In patients who had received the 180-mg dose of denosumab, CTX levels had also returned to baseline 6 months and 12 months after treatment discontinuation. Median levels of P1NP in these patients were 9% and 75.8% higher than baseline levels, at 6 months and 12 months, respectively, after denosumab was stopped.

In addition, the investigators observed that BMD at the lumbar spine and total hip increased during the 12 months of denosumab treatment and then returned to baseline after 12 months of discontinuation of both doses of denosumab.

No osteoporotic fractures were reported during the 12-month denosumab treatment or the 12-month follow-up.

“Postdiscontinuation bone loss in the present study was associated with a return of serum CTX to pretreatment baseline levels in both denosumab groups and an increase in serum P1NP to above baseline levels, particularly in the 180-mg group. These results provide further support for recommendations that patients discontinuing denosumab should transition to follow-on osteoporosis therapy to prevent or minimize remodeling-induced bone loss,” Dr Saag and colleagues concluded.

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