Aaron Broadwell1, Arkadi Chines2, Peter R Ebeling3, Edward Franek4, Shuang Huang2, Shawna Smith2, David Kendler5, Osvaldo Messina6, Paul D Miller7. 1. Rheumatology and Osteoporosis Specialists, Shreveport, Louisiana, USA. 2. Amgen Inc, Thousand Oaks, California, USA. 3. Monash University, Clayton, Victoria, Australia. 4. Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. 5. University of British Columbia, Vancouver, British Columbia, Canada. 6. University of Buenos Aires, Buenos Aires, Argentina. 7. Colorado Center for Bone Research, Lakewood, Colorado, USA.
Abstract
CONTEXT: The effects of long-term exposure to denosumab in individuals with renal insufficiency are unknown. OBJECTIVE: This post hoc analysis evaluates the long-term safety and efficacy of denosumab in individuals with mild-to-moderate chronic kidney disease (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. PARTICIPANTS AND METHODS: Women age 60 to 90 years with a bone mineral density (BMD) T-score of less than -2.5 to greater than -4.0 at the total hip or lumbar spine were randomly assigned 1:1 to receive denosumab 60 mg subcutaneously every 6 months (long-term arm) or placebo (cross-over arm) in FREEDOM; eligible participants could enroll in the extension to receive denosumab 60 mg subcutaneously every 6 months. 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 participants (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; less than 3% progressed to CKD stage 4. Participants in all eGFR subgroups showed similar, persistent BMD gains over time and a low incidence of fractures. The percentage of participants reporting serious AEs was similar among renal subgroups (normal, CKD stage 2, CKD stage 3a, CKD stage 3b) both for 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 participants with mild to moderate CKD.
RCT Entities:
CONTEXT: The effects of long-term exposure to denosumab in individuals with renal insufficiency are unknown. OBJECTIVE: This post hoc analysis evaluates the long-term safety and efficacy of denosumab in individuals with mild-to-moderate chronic kidney disease (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. PARTICIPANTS AND METHODS: Women age 60 to 90 years with a bone mineral density (BMD) T-score of less than -2.5 to greater than -4.0 at the total hip or lumbar spine were randomly assigned 1:1 to receive denosumab 60 mg subcutaneously every 6 months (long-term arm) or placebo (cross-over arm) in FREEDOM; eligible participants could enroll in the extension to receive denosumab 60 mg subcutaneously every 6 months. 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 participants (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; less than 3% progressed to CKD stage 4. Participants in all eGFR subgroups showed similar, persistent BMD gains over time and a low incidence of fractures. The percentage of participants reporting serious AEs was similar among renal subgroups (normal, CKD stage 2, CKD stage 3a, CKD stage 3b) both for 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 participants with mild to moderate CKD.
Authors: M Abdalbary; M Sobh; S Elnagar; M A Elhadedy; N Elshabrawy; M Abdelsalam; K Asadipooya; A Sabry; A Halawa; A El-Husseini Journal: Osteoporos Int Date: 2022-06-24 Impact factor: 5.071
Authors: Giandomenico Roviello; Martina Catalano; Carlotta Ottanelli; Roberta Giorgione; Virginia Rossi; Elisabetta Gambale; Chiara Casadei; Ugo De Giorgi; Lorenzo Antonuzzo Journal: Med Oncol Date: 2022-07-14 Impact factor: 3.738
Authors: Ignacio A Portales-Castillo; Cagri Aksu; Sophia Zhao; Ian Strohbehn; Meghan Sise; Elaine W Yu; Sagar U Nigwekar Journal: Kidney Med Date: 2021-09-20