Stopping Denosumab Reverses BMD Gains in Women With Osteoporosis, RA

ATLANTA — Bone mineral density (BMD) gains achieved with short-term denosumab therapy may be lost upon discontinuation in patients with rheumatoid arthritis (RA) who receive treatment with glucocorticoids, according to study results presented at the 2019 American College of Rheumatology (ACR)/Association of Rheumatology Professionals (ARP) Annual Meeting. The findings are consistent with observations in postmenopausal women who receive treatment with denosumab for osteoporosis who do not have RA.

“The optimal timing and type of subsequent bone therapy upon denosumab discontinuation remains an important topic in the field,” Kenneth Saag, MD, a professor of medicine in the Division of Clinical Immunology and Rheumatology at the University of Alabama at Birmingham, said during his presentation.

Denosumab is approved for the treatment of glucocorticoid-induced osteoporosis. In postmenopausal women with osteoporosis, denosumab discontinuation leads to a transient increase in bone turnover above baseline.

To better understand the effects of denosumab discontinuation in patients with RA who received treatment with glucocorticoids, Dr Saag and colleagues analyzed a subgroup of patients from a previous phase 2 study.

The phase 2 study included 218 patients who were randomly assigned to receive denosumab, 60 mg; denosumab, 180 mg; or placebo subcutaneously for 12 months, and were followed for progression of structural damage. Patients were followed for an additional 12 months after denosumab discontinuation for changes in bone turnover and BMD.

A total of 82 patients were included in the subgroup analysis; 26 patients received placebo, 27 patients received denosumab, 60 mg, and 29 patients received denosumab, 180 mg.

After 12 months of denosumab treatment, serum C-terminal telopeptide of type I collagen (CTX) decreased from baseline in both treatment groups. During the off-treatment period, CTX returned to baseline by 18 months and was similar to placebo at 24 months.

BMD increased at the lumbar spine and hip at 12 months with denosumab treatment and returned to baseline levels after 12 months of discontinuation.

“This study confirms the reversable effect of denosumab on bone turnover and bone mineral density,” Dr Saag said. “We need to have an exit strategy [for patients who discontinue denosumab].”

—Melinda Stevens

Reference:

Saag K, McDermott M, Adachi J, et al. Effect of discontinuation of denosumab in subjects with rheumatoid arthritis treated with glucocorticoids [abstract 1876]. Arthritis Rheumatol. 2019;71(suppl 10). Presented at: 2019 ACR/ARP Annual Meeting; November 8-13, 2019; Atlanta, GA https://acrabstracts.org/abstract/effect-of-discontinuation-of-denosumab-in-subjects-with-rheumatoid-arthritis-treated-with-glucocorticoids/. Accessed November 25, 2019.