Denosumab Safety and Efficacy Among Subjects in the FREEDOM Extension Study With Mild-to-Moderate Chronic Kidney Disease.
J Clin Endocrinol Metab. 2020 Nov 19;: Authors: Broadwell A, Chines A, Ebeling PR, Franek E, Huang S, Smith S, Kendler D, Messina O, Miller PD
CONTEXT: Effects of long-term exposure to denosumab in subjects with renal insufficiency are unknown. OBJECTIVE: This post hoc analysis evaluates the long-term safety and efficacy of denosumab in subjects with mild-to-moderate CKD (stages 2 and 3) using data from the pivotal phase 3, double-blind, 3-year FREEDOM (NCT00089791) and open-label, 7-year extension (NCT00523341) studies. SUBJECTS AND METHODS: Women aged 60-90 years with bone mineral density (BMD) T-score <-2.5 to >-4.0 at the total hip or lumbar spine were randomized 1:1 to denosumab 60 mg SC Q6M (long-term arm) or placebo (cross-over arm) in FREEDOM; eligible subjects could enroll in the extension to receive denosumab 60 mg SC Q6M. Change in estimated glomerular filtration rate (eGFR) from study baseline and annualized rates of fracture and adverse events (AEs) were the main outcome measures. RESULTS: Most subjects (1259/1969 [64%] long-term arm; 1173/1781 [66%] crossover arm) with baseline CKD stage 2 or 3 remained within the same CKD subgroup at study completion; <3% progressed to CKD stage 4. Subjects in all eGFR subgroups showed similar, persistent BMD gains over time and a low incidence of fractures. The percentage of subjects reporting serious AEs was similar among renal subgroups (normal, CKD stage 2, CKD stage 3a, CKD stage 3b) for both the long-term (54% vs 52% vs 57% vs 58%) and crossover (43% vs 42% vs 43% vs 68%) arms, except CKD stage 3b subgroup, crossover arm. CONCLUSION: The safety and efficacy of denosumab did not differ among subjects with mild-to- moderate CKD. PMID: 33211870 [PubMed - as supplied by publisher]