FRI0470 EFFECT OF DISCONTINUATION OF DENOSUMAB IN SUBJECTS WITH RHEUMATOID ARTHRITIS TREATED WITH GLUCOCORTICOIDS

Abstract

Background: Denosumab, a monoclonal antibody against RANKL, is approved for the treatment of glucocorticoid (GC) induced osteoporosis (GiOP). In postmenopausal women with osteoporosis, denosumab discon-tinuation leads to a transient increase in bone turnover above baseline, peaking at 12 months from the last dose, and a corresponding decline in bone mineral density (BMD). To better understand the effects of denosu-mab discontinuation in GC-treated patients, we analyzed a subgroup receiving GCs at baseline from a phase 2 study of denosumab in subjects with rheumatoid arthritis (RA), followed for 12 months after denosu-mab discontinuation. Objectives: To evaluate changes in bone turnover and BMD in subjects with RA on GCs treated with denosumab, after discontinuing denosumab for 12 months. Methods: This double-blind, placebo-controlled study enrolled subjects with RA who were randomized to receive denosumab 60 mg, denosumab 180 mg, or placebo subcutaneously for 12 months, and followed for progression of structural damage. Subjects were followed for an additional 12 months after denosumab discontinuation. Outcome measures in this subgroup analysis of subjects treated with GCs at study baseline included percent change from baseline in serum C-terminal telopeptide of type I collagen (CTX) and lumbar spine (LS) and total hip (TH) BMD on-and off-treatment. Baseline mean (SD) prednisone equivalent dose (mg/day) was 6.1 (2.4), 5.2 (2.1), and 6.1 (3.2) in the placebo, denosumab 60 mg, and denosumab 180 mg groups, respectively. Data on CTX are reported as median and interquartile range. Percent changes in LS and TH BMD at each time point were assessed based on a repeated-measures model adjusting for treatment, baseline use of steroids, previous use of biologics, and baseline BMD value. Results: Among 218 subjects in the phase 2 study, 82 (26 placebo, 27 denosumab 60 mg, and 29 denosumab 180 mg) were included in this analysis. After 12 months of denosumab treatment, CTX decreased from baseline in both groups (Figure); in the off-treatment period, CTX returned to baseline by 18 months and was overall similar to placebo at 24 months. BMD increased at the LS and TH at 12 months with denosu-mab treatment (Figure) and returned to baseline levels after 12 months of discontinuation. Conclusion: Like all non-bisphosphonate medications for osteoporosis, denosumab is reversible with discontinuation. In this small subgroup of GC-treated subjects with RA, BMD gains achieved with denosumab were lost upon discontinuation, consistent with observations in postmenopausal women receiving denosumab for osteoporosis. In this analysis of short-term denosumab use in subjects with RA receiving GCs, bone turnover was reduced with denosumab and gradually returned to baseline upon discontinuation, without a clear increase to above-baseline levels in the off-treatment period.