Among patients with rheumatoid arthritis (RA) receiving treatment with glucocorticoids, discontinuation of denosumab leads to a gradual increase in bone turnover, and thus, a return to baseline levels of lumbar spine and total hip bone mineral density (BMD), according to study results published in Arthritis & Rheumatology.
Researchers conducted a randomized, double-blind, placebo-controlled phase 2 study (ClinicalTrials.gov Identifier: NCT00095498) among patients with RA. Patients had received placebo or 60 or 180 mg of denosumab every 6 months for 12 months and were then followed up with for another 12 months after discontinuation. No bone loss prevention therapy was performed during follow-up. Researchers assessed changes in serum C-terminal telopeptide of type I collagen (CTX), procollagen type I N-terminal propeptide (P1NP), and lumbar spine and total hip BMD.
The analysis included 82 patients receiving glucocorticoids at baseline, of whom 26 received placebo, and 27 and 29 received 60 and 180 mg of denosumab, respectively.
Serum CTX and P1NP levels in both denosumab groups were reduced during treatment compared with baseline levels and those of the placebo group. At 6 months after discontinuation, CTX levels returned to pretreatment levels and was maintained until the end of the study. Levels of P1NP also returned to pretreatment levels at 6 months follow-up in the 60-mg-group and were significantly higher than those of the placebo group at 12 months during the off-treatment period (median percent change, 15.3%; P =.017). In the 180-mg-denosumab group, P1NP returned to pretreatment levels by 6 months off-treatment and was significantly higher than that of the placebo group at 6 months (9.0%; P =.018) and 12 months (75.8%; P =.002) in the off-treatment period.
During the treatment period, gains in lumbar spine and total hip BMD relative to baseline and placebo were reported in both denosumab groups. At 12 months after treatment, lumbar spine BMD had decreased to placebo levels and was slightly greater than pretreatment levels. Total hip BMD values decreased during the off-treatment period and reverted to levels similar to or slightly greater than those of the placebo group. There were no reports of osteoporotic fractures during or after treatment.
Study limitations included the short follow-up period, relatively small sample sizes, and the post-hoc design of the study. In addition, fluctuations in glucocorticoid use were not recorded and the study was not designed to identify effective BMD loss mitigation therapies.
Researchers concluded, “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.”
Disclosure: This research was supported by Amgen Inc. Please see the original reference for a full list of authors’ disclosures.
Saag KG, McDermott MT, Adachi J, et al. The effect of discontinuing denosumab in patients with rheumatoid arthritis treated with glucocorticoids. Arthritis Rheumatol. Published online September 17, 2021. doi:10.1002/art.41981