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

Christopher P. Recknor, Robert R. Recker, Charles T. Benson, Deborah A. Robins, Alan Y. Chiang, Jahangir Alam, Leijun Hu, Toshio Matsumoto, Hideaki Sowa, John H. Sloan, Robert J. Konrad, Bruce H. Mitlak, Adrien A. Sipos

Research output: Contribution to journalArticle

42 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1717-1725
Number of pages9
JournalJournal of Bone and Mineral Research
Volume30
Issue number9
DOIs
StatePublished - Sep 1 2015

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Bone Density
Randomized Controlled Trials
Placebos
Therapeutics
Pelvic Bones
Spine
blosozumab
Serum
Antibodies, Monoclonal, Humanized
Anabolic Agents
Collagen Type I
Osteogenesis
Osteoporosis
Anti-Idiotypic Antibodies
Body Mass Index
Bone and Bones

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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. / Recknor, Christopher P.; Recker, Robert R.; Benson, Charles T.; Robins, Deborah A.; Chiang, Alan Y.; Alam, Jahangir; Hu, Leijun; Matsumoto, Toshio; Sowa, Hideaki; Sloan, John H.; Konrad, Robert J.; Mitlak, Bruce H.; Sipos, Adrien A.

In: Journal of Bone and Mineral Research, Vol. 30, No. 9, 01.09.2015, p. 1717-1725.

Research output: Contribution to journalArticle

Recknor, CP, Recker, RR, Benson, CT, Robins, DA, Chiang, AY, Alam, J, Hu, L, Matsumoto, T, Sowa, H, Sloan, JH, Konrad, RJ, Mitlak, BH & Sipos, AA 2015, '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', Journal of Bone and Mineral Research, vol. 30, no. 9, pp. 1717-1725. https://doi.org/10.1002/jbmr.2489
Recknor, Christopher P. ; Recker, Robert R. ; Benson, Charles T. ; Robins, Deborah A. ; Chiang, Alan Y. ; Alam, Jahangir ; Hu, Leijun ; Matsumoto, Toshio ; Sowa, Hideaki ; Sloan, John H. ; Konrad, Robert J. ; Mitlak, Bruce H. ; Sipos, Adrien A. / 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. In: Journal of Bone and Mineral Research. 2015 ; Vol. 30, No. 9. pp. 1717-1725.
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