Article
Reference
T-score as an indicator of fracture risk during treatment with romosozumab or alendronate in the ARCH trial
COSMAN, Felicia, et al.
Abstract
In the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) clinical trial (NCT01631214), 1 year of romosozumab followed by alendronate reduced the risk of vertebral and nonvertebral fractures compared to alendronate alone in women with prevalent fracture. We performed post hoc analyses of data from patients in ARCH (romosozumab, n = 1739; alendronate, n = 1726) who had a baseline BMD measurement and received at least one open-label alendronate dose. We evaluated 1-year mean BMD and corresponding T-score changes; proportions of patients achieving T-scores >
-2.5 at the total hip (TH), femoral neck (FN), and lumbar spine (LS); and group differences in fracture rates after 12 months, while all participants were on alendronate.[...]
COSMAN, Felicia, et al. T-score as an indicator of fracture risk during treatment with
romosozumab or alendronate in the ARCH trial. Journal of Bone and Mineral Research, 2020, vol. 35, no. 7, p. 1333-1342
PMID : 32445228
DOI : 10.1002/jbmr.3996
Available at:
http://archive-ouverte.unige.ch/unige:143606
Disclaimer: layout of this document may differ from the published version.
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Supplemental Material
T-Score as an Indicator of Fracture Risk During Treatment With Romosozumab or Alendronate in the ARCH Trial
Felicia Cosman,1 E. Michael Lewiecki,2 Peter R. Ebeling,3 Eric Hesse,4 Nicola Napoli,5 Toshio Matsumoto,6 Daria B. Crittenden,7 Maria Rojeski,7 Wenjing Yang,7 Cesar Libanati,8 Serge Ferrari9
1Columbia University, New York, NY, USA; 2New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM, USA; 3Monash University, Melbourne, Australia; 4Institute of Molecular Musculoskeletal Research, Faculty of Medicine, LMU Munich, Munich, Germany;
5Campus Bio-Medico University of Rome, Rome, Italy; 6University of Tokushima, Fujii Memorial Institute of Medical Sciences, Tokushima, Japan; 7Amgen Inc., Thousand Oaks, CA, USA; 8UCB Pharma, Brussels, Belgium; 9Geneva University Hospital, Geneva, Switzerland
Corresponding author
Felicia Cosman, MD. Columbia University College of Physicians and Surgeons; 630 W 168th St, New York, NY 10032, USA; e-mail: fc14@cumc.columbia.edu; phone: +1 845-480-4479
Funding: Amgen Inc., Astellas, and UCB Pharma sponsored this study.
Target journal: JBMR
Supplemental material: 3 (2 figures / 1 table)
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Supplemental Figure 1. ARCH study design
Women were randomly assigned, in a 1:1 ratio, to receive romosozumab 210 mg by subcutaneous injection once monthly or alendronate 70 mg orally every week for 12 months for the double-blind period of the trial, followed by open-label alendronate until the time of the primary analysis; the initial treatment assignment remained blinded. The primary analysis was performed when events of clinical fracture (nonvertebral and symptomatic vertebral fractures) had been confirmed in at least 330 patients and all the patients had completed the Month 24 visit. The median (quartile 1, quartile 3) follow-up time through primary analysis (double-blind plus open-label) was 2.7 (2.2, 3.3) years. BMD was assessed at the lumbar spine and proximal femur in all the patients at baseline and every 12 months thereafter (filled ovals). BMD was also assessed at Month 6 in a subset of patients (open oval), with 143 patients with a Month 6 BMD T-score measurement.
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Supplemental Table 1. Mean BMD Percentage Changes From Baseline, Mean BMD T-score Changes From Baseline, and Mean BMD T-scores Achieved at the Total Hip, Femoral Neck, and Lumbar Spine at Month 24
Romosozumab-to-Alendronate (N = 1739a)
Alendronate-to-Alendronate (N = 1726a)
Mean BMD percentage change
Mean T-score change
Mean T-score achieved
Mean BMD percentage change
Mean T-score change
Mean T-score achieved Total hip 7.3 (7.1, 7.6) 0.37 (0.36, 0.38) –2.40 (–2.41, –2.39) 3.5 (3.3, 3.7) 0.18 (0.17, 0.19) –2.59 (–2.60, –2.58) Femoral neck 6.1 (5.8, 6.5) 0.28 (0.27, 0.29) –2.60 (–2.61, –2.59) 2.3 (2.0, 2.6) 0.11 (0.10, 0.12) –2.77 (–2.78, –2.76) Lumbar spine 15.5 (15.1, 15.9) 1.01 (0.99, 1.04) –1.97 (–1.99, –1.94) 7.3 (7.0, 7.6) 0.48 (0.46, 0.50) –2.50 (–2.52, –2.48)
For BMD percentage change, data are mean % (95% CI). For T-score change and T-score achieved, data are least squares mean (95% CI) based on an ANCOVA model adjusting for treatment, age (<75 versus ≥75 years), presence of severe vertebral fracture at baseline, baseline BMD value or T-score, machine type, and baseline BMD value or T-score-by-machine type interaction. N = Number of patients with BMD values at baseline and at least 1 open-label alendronate dose. aN values shown are for total hip and femoral neck; for lumbar spine, N = 1665 for
romosozumab-to-alendronate and 1647 for alendronate-to-alendronate. Missing values were imputed by carrying forward the last non-missing post-baseline value prior to the missing value and within the treatment period. P < 0.001 for difference between romosozumab-to-alendronate and alendronate-to-alendronate for all comparisons at the three skeletal sites. ANCOVA = analysis of covariance.
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Supplemental Figure 2. Percentage of patients with achieved T-score > –2.5 and > –2.0 at the total hip (Panel A), femoral neck (Panel B), and lumbar spine (Panel C) at Month 24
n/N1 = number of patients with T-score change above the threshold/number of patients with an evaluation at that timepoint. The analysis included patients with BMD values at baseline and at least 1 open-label alendronate dose. P-values were based on a logistic regression model adjusting for treatment, age strata (<75 versus ≥75 years), presence of severe vertebral
fracture at baseline, and baseline T-score. Missing values were imputed by carrying forward the last non-missing post-baseline value prior to the missing value and within the treatment period.
