Posted by Phillipa on May 3, 2011, at 0:02:25
Denosumab another osteoporosis med after the Freedom Trial Deemed Safe And Avoids Femur Fx's Osteonecrosis of Jaw, Fractures. Six Month Injections. Phillipa
From Medscape Medical News
FREEDOM Trial: Long-Term Denosumab Safe, Efficacious for BMD
Barbara BoughtonAuthors and Disclosures
Information from Industry
Changes in bone remodeling following menopause result in bone loss
An osteoporosis expert speaks about bone remodeling and its role in osteoporosis.
View presentation May 2, 2011 (San Diego, California) Results from the first 2 years of the international multicenter open-label Fracture Reduction Evaluation of Denosumb in Osteoporosis Every 6 Months (FREEDOM) trial extension, testing denosumab (Prolia, Amgen Pharmaceuticals) in 4550 postmenopausal women with osteoporosis, showed that the drug maintains its efficacy in improving bone mineral density (BMD) and reducing the incidence of fractures over 5 years without any increase in adverse events, according to researchers here at the American Association of Clinical Endocrinologists (AACE) 20th Annual Meeting and Clinical Congress.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 lumbar spine and hip up to 5 years and a low incidence rate of new fractures, according to presenting author Cesar Libanati, MD, clinical research medical director at Amgen.
In the FREEDOM trial extension, the yearly incidence rate of new vertebral fractures ranged from 0.9% to 1.4%, whereas the yearly incidence rate of nonvertebral fractures ranged from 1.1% to 2.4%, according to Dr. Libanati.
Reported adverse and serious adverse events, which have become an increasing concern with antiresorptive agents (particularly the bisphosphonates), did not increase over time in the FREEDOM trial extension, Dr. Libanati reported. There have been no cases of atypical femoral fractures to date, and only 2 cases of osteonecrosis of the jaw both of which healed completely without further complications. One of these patients is still receiving denosumab, Dr. Libanati said.
In the FREEDOM phase 3 clinical trial, the efficacy and safety of 3 years of denosumab treatment was compared with placebo. The data from that trial were the cornerstone of the drug's approval for osteoporosis in June 2010.
In the extension trial, 2342 women from the denosumab group in the original 3-year FREEDOM trial and 2207 women from the placebo group were treated with denosumab 60 mg every 6 months, along with daily doses of calcium and vitamin D. The women in the extension trial (those treated for 5 years and those who crossed over to denosumab) had characteristics similar to those in the original FREEDOM trial. However, there were significantly more women 75 years and older in the extension trial (53.7% from the long-term treatment group and 52.2% from the crossover treatment group) than in the in the original FREEDOM trial (28.3%).
In the fourth and fifth year of denosumab treatment, those in the original intervention group experienced further benefits in BMD of the lumbar spine and hip. In the fourth year, BMD of the lumbar spine increased by 1.9% in the long-term treatment group and BMD of the hip increased by 0.7%. In the fifth year of treatment, BMD of the lumbar spine increased by 1.7% in the long-term treatment group and BMD of the total hip increased by 0.6%.
The de novo group in the extension trial experienced improvements in BMD similar to those seen in the intervention group in the first 2 years of the original FREEDOM trial. In the first 2 years of their treatment, the crossover group experienced a 7.9% increase in lumbar spine BMD and a 4.1% increase in total hip BMD (P < .0001, compared with baseline). Markers of bone turnover were improved to a similar extent in this group and in those in the intervention group of the original FREEDOM trial.
The yearly incidence of new vertebral fractures was 1.4% in the long-term denosumab group and 0.9% in the crossover group. Rates of new nonvertebral fractures were also low, with a yearly incidence of 1.4% in the fourth year and 1.1% in the fifth year for the long-term treatment group, Dr. Libanati said. In contrast, the yearly incidence rate of new nonvertebral fractures in the crossover group was 2.4% in the first year of treatment and 1.7% in the second year of treatment.
The incidence of serious adverse events were low, with just 2 cases of osteonecrosis of the jaw and 1 case of cellulitis in the crossover group of the extension trial. Three subjects in the long-term treatment group experienced cellulitis, but there were no cases of osteonecrosis of the jaw in this group, according to Dr. Libanati.
"The striking data from the FREEDOM trial extension is the continued significant increases in bone mineral density and fracture protection for those on long-term treatment with denosumab. Their bone mineral density continued to increase in the fourth and fifth year on the drug," said Pauline Camacho, MD, associate professor of medicine at Loyola University Medical Center, director of the Loyola University Osteoporosis Metabolic Bone Disease Center in Maywood, Illinois, and a member of the board of directors of AACE.
"The 10-year data from the FREEDOM trial will be very important because we need long-term safety data about antiresorptive drugs, particularly given the report of atypical fractures from bisphosphonates," Dr. Camacho said. Although atypical fractures are an increasing concern with antiresorptive drugs, it's encouraging that the FREEDOM trial extension showed no increased incidence of this complication, she noted.
"In the original FREEDOM trial, the incidence of serious cellulitis (experienced by 12 patients who received denosumab) was a concern," Dr. Camacho said. Because denosumab is a relatively young drug, it is difficult to know whether this incidence of cellulitis indicates a negative effect on the immune system, she noted.
"We do need to warn patients about the chance of cellulitis with denosumab, but it was reassuring that there was not much cellulitis in the extension data," Dr. Camacho added.
The 2-year results of the FREEDOM trial extension reinforce the data on denosumab as a potent osteoporosis medication and provides another treatment option for those who cannot tolerate oral drugs because of gastrointestinal adverse effects, Dr. Camacho emphasized. In addition to its convenient twice-yearly administration, it is a drug that can be used in patients with renal insufficiency, she noted.
Dr. Libanati is an employee of and owns stock in Amgen Pharmaceuticals. Dr. Camacho reports receiving research support from Eli Lilly and Company and Proctor & Gamble.
American Association of Clinical Endocrinologists (AACE) 20th Annual Meeting and Clinical Congress: Abstract 503. Presented April 14, 2011
poster:Phillipa
thread:984422
URL: http://www.dr-bob.org/babble/20110502/msgs/984422.html