Bente L Langdahl1, Stuart Silverman2, Saeko Fujiwara3, Ken Saag4, Nicola Napoli5, Satoshi Soen6, Hiroyuki Enomoto7, Thomas E Melby8, Damon P Disch9, Fernando Marin10, John H Krege11. 1. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. Electronic address: bente.langdahl@aarhus.rm.dk. 2. Cedars-Sinai/UCLA Medical Center and OMC Clinical Research Center, Beverly Hills, CA, USA. Electronic address: stuarts@bhillsra.com. 3. Health Management and Promotion Center, Hiroshima Atomic Bomb Casualty Council, Hiroshima, Japan. 4. Division of Clinical Immunology and Rheumatology, Center for Education and Research on Therapeutics University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: ksaag@uabmc.edu. 5. Division of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Rome, Italy; IRCCS Istituto Ortopedico Galeazzi, Milan, Italy. 6. Department of Orthopaedic Surgery and Rheumatology, Kindai University Nara Hospital, Ikoma, Japan. Electronic address: souen@med.kindai.ac.jp. 7. Eli Lilly Japan K.K., Kobe, Japan. Electronic address: enomoto_hiroyuki@lilly.com. 8. Syneos Health, Raleigh, NC, USA. Electronic address: thomas.melby@syneoshealth.com. 9. Eli Lilly and Company, Indianapolis, IN, USA. 10. Lilly Research Centre, Windlesham, UK. Electronic address: marin_fernando@lilly.com. 11. Eli Lilly and Company, Indianapolis, IN, USA. Electronic address: krege_john_henry@lilly.com.
Abstract
INTRODUCTION: Teriparatide significantly reduces fracture rates in clinical trials; however, those study populations were relatively restricted and included too few patients to analyze fracture outcomes within clinically important patient subgroups. We assessed fracture outcomes in subgroups of osteoporosis patients from 4 real-world teriparatide observational studies. METHODS: Patients received teriparatide 20 μg/day for up to 24 months. Fracture rates were compared between 0 to 6 months versus >6 months using a piecewise exponential model for first fracture. Analyses included incident clinical vertebral fractures (CVF) and nonvertebral fractures (NVF), and clinical fractures (CVF and NVF) by subgroups of gender, age <75 or ≥75 years, diabetes, prior bisphosphonates use, rheumatoid arthritis (RA), glucocorticoid use, prior hip, and prior vertebral fracture. RESULTS: The population included 8828 patients (8117 women, 92%) with mean (SD) age 71 (10.6) years and teriparatide treatment duration 17.4 (8.6) months. Overall, CVF, NVF, clinical fracture, and hip fracture rates decreased by 62%, 43%, 50%, and 56%, respectively (all p < .005) for >6 months versus 0 to 6 months. Subgroup analyses all showed significantly decreased rates after >6 months except for NVF reduction in males (n = 710, fracture rate low during months 0 to 6) and in patients using glucocorticoids, and CVF in patients with prior hip fracture. The effects of teriparatide on CVF, NVF, and clinical fractures over time were statistically consistent in all subgroups except age for CVF (p = .074, patients <75 years of age responded better), and diabetes for clinical fractures (p = .046, patients with diabetes responded better), although all of these subgroups experienced significant reductions over time. Glucocorticoids, prior bisphosphonate, and prior vertebral fracture were associated with increased CVF, NVF, and clinical fracture rates; RA, prior hip fracture and female gender were associated with higher NVF and clinical fracture rates; increased age was associated with higher CVF and clinical fracture rates. CONCLUSIONS: Data from 4 real-world observational studies showed statistically significant reductions during teriparatide treatment in rates of CVF, NVF, and clinical fractures in clinically relevant patient subgroups. These results should be interpreted in the context of the non-controlled design of the source studies.
INTRODUCTION:Teriparatide significantly reduces fracture rates in clinical trials; however, those study populations were relatively restricted and included too few patients to analyze fracture outcomes within clinically important patient subgroups. We assessed fracture outcomes in subgroups of osteoporosispatients from 4 real-world teriparatide observational studies. METHODS:Patients received teriparatide 20 μg/day for up to 24 months. Fracture rates were compared between 0 to 6 months versus >6 months using a piecewise exponential model for first fracture. Analyses included incident clinical vertebral fractures (CVF) and nonvertebral fractures (NVF), and clinical fractures (CVF and NVF) by subgroups of gender, age <75 or ≥75 years, diabetes, prior bisphosphonates use, rheumatoid arthritis (RA), glucocorticoid use, prior hip, and prior vertebral fracture. RESULTS: The population included 8828 patients (8117 women, 92%) with mean (SD) age 71 (10.6) years and teriparatide treatment duration 17.4 (8.6) months. Overall, CVF, NVF, clinical fracture, and hip fracture rates decreased by 62%, 43%, 50%, and 56%, respectively (all p < .005) for >6 months versus 0 to 6 months. Subgroup analyses all showed significantly decreased rates after >6 months except for NVF reduction in males (n = 710, fracture rate low during months 0 to 6) and in patients using glucocorticoids, and CVF in patients with prior hip fracture. The effects of teriparatide on CVF, NVF, and clinical fractures over time were statistically consistent in all subgroups except age for CVF (p = .074, patients <75 years of age responded better), and diabetes for clinical fractures (p = .046, patients with diabetes responded better), although all of these subgroups experienced significant reductions over time. Glucocorticoids, prior bisphosphonate, and prior vertebral fracture were associated with increased CVF, NVF, and clinical fracture rates; RA, prior hip fracture and female gender were associated with higher NVF and clinical fracture rates; increased age was associated with higher CVF and clinical fracture rates. CONCLUSIONS: Data from 4 real-world observational studies showed statistically significant reductions during teriparatide treatment in rates of CVF, NVF, and clinical fractures in clinically relevant patient subgroups. These results should be interpreted in the context of the non-controlled design of the source studies.
Authors: Fjorda Koromani; Samuel Ghatan; Mandy van Hoek; M Carola Zillikens; Edwin H G Oei; Fernando Rivadeneira; Ling Oei Journal: Curr Osteoporos Rep Date: 2021-01-12 Impact factor: 5.096
Authors: Kaleen N Hayes; Ulrike Baschant; Barbara Hauser; Andrea M Burden; Elizabeth M Winter Journal: Front Endocrinol (Lausanne) Date: 2021-12-15 Impact factor: 5.555
Authors: Adi Cohen; Stephanie Shiau; Nandini Nair; Robert R Recker; Joan M Lappe; David W Dempster; Thomas L Nickolas; Hua Zhou; Sanchita Agarwal; Mafo Kamanda-Kosseh; Mariana Bucovsky; John M Williams; Donald J McMahon; Julie Stubby; Elizabeth Shane Journal: J Clin Endocrinol Metab Date: 2020-10-01 Impact factor: 5.958