Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Long-Term Denosumab Treatment of Postmenopausal Women with Osteoporosis: Results from the First Year Extension Study of the FREEDOM Trial.
Chapurlat6, Roland, Papapoulos11, Socrates, Bone12, Henry G., Brandi16, Maria L., Brown10, Jacques, Czerwinski9, Edward, Daizadeh1, Nadia S.
Amgen Inc, Thousand Oaks, CA
Laval University Department of Medicine, Quebec, QC, Canada
Leiden University Medical Center, Leiden, The Netherlands
Michigan Bone and Mineral Clinic, PC, Detroit, MI
Osteoporosis Clinic, Center for Bone Research at the Sahlgrenska, Goteborg, Sweden
SF Coordinating Center, San Francisco, CA
St. Vincent Hospital Medical University, Vienna, Austria
University of Florence, Florence, Italy
University of Leige, Leige, Belgium
Amgen Inc., San Francisco, CA
Amgen Inc., Thousand Oaks, CA
Centre Hospitalier Universitaire Vaudois, Lusanne, Switzerland
Centro TIEMPO, Buenos Aires, Argentina
Hopital E. Herriot, Lyon, France
Hospital de Clinicas da Universidade Federal do Parana, Curitiba, Brazil
Jefe Servicio Reumatologia, Valencia, Spain
Krakowskie Centrum Medyczne, Krakow, Poland
FREEDOM was the pivotal 3-year Phase 3 study to establish the efficacy and safety of denosumab for the treatment of osteoporosis in postmenopausal women. The open-label extension of FREEDOM will evaluate the long-term (up to 10 years) efficacy and safety of denosumab. We report here first year results of this extension study, representing up to 48 continuous months of denosumab exposure.
Subjects enrolled in the extension study previously completed the FREEDOM trial. All subjects received subcutaneous denosumab (60 mg) injection every 6 months during the extension study and continued to take daily calcium (1 g) and vitamin D (>=400 IU) supplements. For those randomized to the denosumab arm in FREEDOM (long-term group), the data reported here reflect a total of up to 8 injections of denosumab. For those previously assigned to placebo (de novo group), the data are from exposure of up to 2 doses of denosumab for 12 months. Changes in bone mineral density (BMD) and bone turnover markers (BTM) over 12 and 48 months are reported for subjects enrolled in the extension. No formal statistical testing was planned for this interim report. P-values are descriptive.
A total of 4550 (70.2%) subjects from FREEDOM were enrolled in the extension study: 2343 in the long-term and 2207 in the de novo group. The long-term group had a further 2.0% and 0.8% increase in lumbar spine and total hip BMD, respectively, during the 4th year of denosumab administration (P<0.0001 compared to baseline BMD of the extension study; see Figure). The total increase over the 48 months treatment with denosumab in lumbar spine and total hip BMD was 12.1% and a 6.5%, respectively. The de novo group had a 6.0% and 1.7% increase in lumbar spine and total hip BMD, respectively, during their 1st year of treatment with denosumab in the extension study (P<0.0001 compared to baseline BMD). The serum C-telopeptide (CTX) reduction profiles after denosumab initiation, and the increase in CTX levels at the end of the dosing period, were similar for the long-term and de novo groups. Adverse events (AEs) were reported by 70.4% and 67.9% of subjects in the long-term and de novo groups, respectively. Serious AEs were reported by 9.8% and 11.2% of subjects in the long-term and de novo group, respectively.
Figure copyright 2010, American Society for Bone and Mineral Research. Used by permission. All rights reserved.
Percentage Change in BMD With Denosumab Treatment for 4 Years (Long-term) or 1 Year (De Novo)
These results suggest that treating postmenopausal women with osteoporosis with denosumab for 48 months continues to significantly reduce bone resorption and further increase BMD. Long-term treatment decreases BTM with a similar pattern and to a similar degree as observed in the first year of treatment.
To cite this abstract, please use the following information:
Chapurlat, Roland, Papapoulos, Socrates, Bone, Henry G., Brandi, Maria L., Brown, Jacques, Czerwinski, Edward, et al; Long-Term Denosumab Treatment of Postmenopausal Women with Osteoporosis: Results from the First Year Extension Study of the FREEDOM Trial. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2157