Methods study design and participants designs of the freedom trial and open. Denosumab reduces bone resorption and improves bone mineral density bmd. Pdf vertebral fractures following discontinuation of. Denosumab for 10 years is safe, effective in older women. In the multicentre, randomised, doubleblind, placebocontrolled, phase 3 freedom trial, postmenopausal women aged 6090 years with osteoporosis were enrolled in 214 centres in north america, europe, latin america, and australasia and were randomly assigned 1. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. Overview of the study and outcomes the freedom study was an international randomized, placebocontrolled trial designed to test the effect of denosumab on fracture risk in postmenopausal women during a 3year followup period. Romosozumab treatment in postmenopausal women with. Freedom trial, denosumab treatment significantly reduces the incidence of new vertebral, nonvertebral, and hip fractures compared with placebo treatment. Longterm efficacy and safety data are therefore of great importance. Denosumab, however, is wellsuited for use in primary care. Vertebral fractures after discontinuation of denosumab. Pdf discontinuation of denosumab and associated fracture.
Methods study design our study, called fracture reduction evaluation of denosumab in osteoporosis every 6 months freedom, was an international, randomized, placebocontrolled trial. Invasive oral procedures and events in postmenopausal women. The freedom trial the college of family physicians of canada. The freedom study was a 3year international multicentre trial with a. The amgen denosumab freedom trial the healthcare channel.
Denosumab discontinuation increases bone turnover markers 3 months. Appendix investigators for the freedom trial are as follows. A recent post hoc analysis of the denosumab phase 3 randomised trial freedom and its extension study demonstrated a small but significant increase in the risk of multiple vertebral fractures. Denosumab showed benefit in several phase 3 or 4 studies in pm women with osteoporosis or low bone mineral density bmd, including the pivotal 3year doubleblind freedom trial and its 7year openlabel extension. Denosumab for prevention of fractures in postmenopausal women.
The freedom trial demonstrated that in patients with dm and angiographicallyconfirmed multivessel cad. The freedom trial is the largest randomized controlled trial to compare denosumab with placebo in the prevention of fractures in postmenopausal. Denosumab circulates in blood and extracellular fluid including bone tissue1,4 control denosumab blood vessel tibial cortex the freedom trial fracture reduction evaluation of denosumab in osteoporosis every 6 months the effects of denosumab on vertebral, nonvertebral, and hip fracture in women with osteoporosis. The freedom trial placebo, n 3,906 3,799 3,672 3,538 3,430 3,311 3,221. Subjects who were randomized to denosumab in the freedom trial, continued into the extension study, completed the 10. Op0306 ten years of denosumab treatment in postmenopausal. Johnson, pharmd, bcps, shenandoah university bernard j. Denosumab is an option for treatment of osteoporosis. The objective of the trial is to evaluate the risk versus benefit of denosumab in maintenance setting in patients requiring longterm use 1 year of denosumab. Recent results from the fracture reduction evaluation of denosumab in osteoporosis every 6 months freedom trial and its extension regarding bone histology, histomorphometry, and matrix mineralization, as well as areal bone mineral density bmd, fracture incidence, and adverse events, showed efficacy and safety of longterm denosumab treatment of osteoporosis in postmenopausal women. Several phase 2 and phase 3 randomized controlled trials have evaluated the efficacy of denosumab, but only one, the fracture reduction evaluation of denosumab in osteoporosis every 6 months freedom trial, included fracture reduction as the primary outcome measure.
Denosumab dmab is a fully human monoclonal antibody that binds rankl and was associated with fracture risk reduction in the freedom trial. Denosumab prolia for treatment of postmenopausal osteoporosis author gretchen l. Discontinuation of denosumab and associated fracture incidence. The clinical trials on this list are studying denosumab. Pdf 10 years of denosumab treatment in postmenopausal. The freedom trial, including the extension, will run for a total of 10 years, but the analysis presented here indicates that treatment with denosumab provides yearly improvements in bmd of the. Clinical trials using denosumab national cancer institute. Denosumab for reducing risk of fractures in postmenopausal. Denosumab for treatment of osteoporosis in postmenopausal women. Decade of data on denosumab for osteoporosis reassuring. The pivotal phase 3 fracture endpoint trial, called the fracture reduction evaluation of denosumab in osteoporosis freedom study, enrolled 7808 healthy postmenopausal women with osteoporosis who were randomly assigned to receive placebo or denosumab 60 mg subcutaneously q6m. May 01, 2019 the freedom trial is the largest randomized controlled trial to compare denosumab with placebo in the prevention of fractures in postmenopausal women with osteoporosis. Background osteoporosis is an important chronic disease, requiring prolonged treatment.
Denosumab for the treatment of osteoporosis sciencedirect. Update on denosumab treatment in postmenopausal women with. The freedom trial was a prospective, randomized, multicenter superiority trial that compared multivessel pci to cabg in diabetic patients on optimal medical therapy. No direct comparisons are available, but denosumab appears to provide greater reduction in fragility fractures than oral bisphosphonates do. Aug 08, 2018 this study is a multicenter, multinational, open label, single arm phase 2 study of singleagent denosumab. Thus, results from the freedom placebocontrolled trial conducted in postmenopausal women were accepted to inform the use of denosumab for osteoporosis. This phase ii trial studies how well denosumab works in treating patients with multiple myeloma with kidney insufficiency. Known sensitivity to mammalian cellderived drug products. Our study, called fracture reduction evaluation of denosumab in osteoporosis every 6 months freedom, was an international, randomized, placebocontrolled trial. Treatment guidelines vary across geographies, and clearly treatment decisions in clinical practice will take into consideration individual characteristics and local guidelines.
Safety observations with 3 years of denosumab exposure. We also report effects on fracture rates and bmd, as well as bone histology and remodelling. Six years of denosumab treatment in postmenopausal women with osteoporosis. Original article from the new england journal of medicine denosumab for prevention of fractures in postmenopausal women with osteoporosis.
The freedom trial nct00089791 and its extension nct00523341 are both registered with clinicaltrials. New and emerging concepts in the use of denosumab for the. Clinical trials are research studies that involve people. Clinical trials look at new ways to prevent, detect, or treat disease. Analysis from the fracture reduction evaluation of denosumab in osteoporosis every 6 months freedom trial jacques p brown,1 christian roux,2 ove to. Investigators for the fracture reduction evaluation of denosumab in osteoporosis every 6 months freedom trial are listed in the appendix. Denosumab for prevention of fractures in postmenopausal.
Reduced dosedensity of denosumab for unresectable gctb. The first randomised, placebocontrolled trial of denosumab with fracture as a primary outcome was the fracture reduction evaluation of denosumab in osteoporosis every six months freedom trial, published in 2009. Immunotherapy with monoclonal antibodies, such as denosumab, may help the bodys immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The freedom trial demonstrated that denosumab, a monoclonal antibody, is efficacious in vertebral, hip, and nonvertebral fracture reduction in postmenopausal osteoporosis. Aug 11, 2009 principle investigator steven cummings discusses the trial of denosumab to prevent osteoporotic fractures. We hypothesized that dmab treatment decreased fasting serum glucose fsg relative to placebo in women with diabetes or prediabetes enrolled in freedom trial. Its efficacy in reducing the risk of fracture has been shown in a large prospective, randomized multicenter study of 7868 postmenopausal women with osteoporosis the freedom trial. The effects of dmab treatment for up to 10 years have been evaluated in the 3year freedom. Currently enrolled in an investigational device or drug trial s or it has not been at least 30 days since the last study visit in an investigational device or drug trial s, or subject is receiving other investigational agents. Denosumab is a fully human monoclonal antibody to the receptor. Denosumab has recently been approved for treatment of postmenopausal osteoporosis. Denosumab treatment in postmenopausal women with osteoporosis. In the freedom trial n 7,868, compared with the placebo. Abstractdenosumab is a novel antiresorptive drug that has been approved for use as a firstline drug for primary and secondary prevention of osteoporotic fractures.
Denosumab dmab is used in over 80 countries or administrative districts worldwide for the treatment of postmenopausal women with osteoporosis. All trials on the list are supported by nci ncis basic information about clinical trials explains the types and phases of trials and how they are carried out. Notably, additional analyses from the freedom trial have shown that fracture risk reduction with denosumab is more pronounced in participants at moderatetohigh risk. The freedom trial showed that denosumab was effective in reducing the risk. All participants who completed the freedom trial without discontinuing treatment or missing more than one dose of investigational product were eligible to enrol in the openlabel, 7year extension, in which all participants received denosumab. Our study, called fracture reduction evaluation of denosumab in osteoporosis every 6 months. Analysis from the fracture reduction evaluation of denosumab in osteoporosis every 6 months freedom trial. Comparison between subjects who received denosumab during the randomized freedom trial and subjects who crossed over to denosumab during the freedom extension. The freedom study was an international randomized, placebocontrolled trial designed to test the effect of denosumab on fracture risk in postmeno. The fracture reduction evaluation of denosumab in osteoporosis every 6 months freedom study was an international, randomized, placebocontrolled 3year trial in which subcutaneous denosumab injection, 60 mg every 6 months, reduced the risk for new vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis compared. Although all patients made the transition to denosumab in the second year of the trial, the risk of fracture was lower in the group that had received romosozumab in the first year than in the. In the phase 3 freedom trial, 7808 postmenopausal women aged 60 to 91 who had osteoporosis were randomized to receive a subcutaneous injection of 60 mg of denosumab or placebo every 6 months for 3. Pdf 10 years of denosumab treatment in postmenopausal women. Effect of denosumab on fasting glucose in women with diabetes.