title: The Effect of Discontinuing Treatment With Blosozumab: Follow-up Results of a Phase 2 Randomized Clinical Trial in Postmenopausal Women With Low Bone Mineral Density.
abstract: Administration of blosozumab, a humanized monoclonal antibody that binds sclerostin, increases bone formation and bone mineral density (BMD) in postmenopausal women with low BMD. To evaluate the effect of discontinuing blosozumab, we studied women enrolled in a 1-year randomized, placebo-controlled phase 2 trial for an additional year after they completed treatment. Of the 120 women initially enrolled in the study, 106 women completed treatment and continued into follow-up; 88 women completed 1 year of follow-up. At the beginning of follow-up, groups remained balanced for age, race, and body mass index, but lumbar spine and total hip BMD were increased in prior blosozumab groups, reflecting an anabolic treatment effect. At the end of follow-up, 1 year after discontinuing treatment, lumbar spine BMD remained significantly greater than placebo in women initially treated with blosozumab 270 mg every 2 weeks (Q2W) and blosozumab 180 mg Q2W (6.9% and 3.6% above baseline, respectively). Total hip BMD also declined after discontinuation of treatment but at 1 year after treatment remained significantly greater than placebo in women initially treated with blosozumab 270 mg Q2W and blosozumab 180 mg Q2W (3.9% and 2.6% above baseline, respectively). During follow-up, median serum P1NP was not consistently different between the prior blosozumab groups and placebo. A similar pattern was apparent for median serum C-terminal telopeptide of type 1 collagen (CTx) levels, with more variability. Mean serum total sclerostin concentration increased with blosozumab, indicating target engagement, and declined to baseline after discontinuation. There were no adverse events considered related to prior treatment with blosozumab. Anti-drug antibodies generally declined in patients who had detectable levels during prior treatment. These findings support the continued study of blosozumab as an anabolic therapy for treatment of osteoporosis.
authors.affiliation: United Osteoporosis Centers, Gainesville, GA, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Recknor
authors.affiliation: Osteoporosis Research Center, Creighton University, Omaha, NE, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Recker
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Charles T
authors.initials: CT
authors.lastname: Benson
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Robins
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Alan Y
authors.initials: AY
authors.lastname: Chiang
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Jahangir
authors.initials: J
authors.lastname: Alam
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Leijun
authors.initials: L
authors.lastname: Hu
authors.affiliation: Fuji Memorial Institute of Medical Sciences, University of Tokushima, Tokushima, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Lilly Research Laboratories Japan, Kobe, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sowa
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Sloan
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Konrad
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Mitlak
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Adrien A
authors.initials: AA
authors.lastname: Sipos
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000911:Antibodies, Monoclonal / Q000737:chemistry; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000097:blood; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000097:blood* / Q000276:immunology; D001862:Bone Resorption; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D010012:Osteogenesis; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D017698:Postmenopause; D013256:Steroids / Q000737:chemistry; D013997:Time Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human; D013256:Steroids; C000593189:blosozumab
keywords: ANABOLICS; BLOSOZUMAB; DXA; OSTEOPOROSIS; SCLEROSTIN ANTIBODY