Factors associated with high 24-month persistence with denosumab: results of a real-world, non-interventional study of women with postmenopausal osteoporosis in Germany, Austria, Greece, and Belgium

A Fahrleitner-Pammer, N Papaioannou, E Gielen, M Feudjo Tepie, C Toffis, I Frieling, P Geusens, P Makras, E Boschitsch, J Callens, A D Anastasilakis, C Niedhart, H Resch, L Kalouche-Khalil, P Hadji, A Fahrleitner-Pammer, N Papaioannou, E Gielen, M Feudjo Tepie, C Toffis, I Frieling, P Geusens, P Makras, E Boschitsch, J Callens, A D Anastasilakis, C Niedhart, H Resch, L Kalouche-Khalil, P Hadji

Abstract

Persistence with osteoporosis therapy is vital for fracture prevention. This non-interventional study of postmenopausal women receiving denosumab in Germany, Austria, Greece, and Belgium found that persistence with denosumab remains consistently high after 24 months in patients at high risk of fracture.

Purpose: Continued persistence with osteoporosis therapy is vital for fracture prevention. This non-interventional study of clinical practice evaluated medication-taking behavior of postmenopausal women receiving denosumab in Germany, Austria, Greece, and Belgium and factors influencing persistence.

Methods: Subcutaneous denosumab (60 mg every 6 months) was assigned according to prescribing information and local guidelines before and independently of enrollment; outcomes were recorded during routine practice for up to 24 months. Persistence was defined as receiving the subsequent injection within 6 months + 8 weeks of the previous injection and adherence as administration of subsequent injections within 6 months ± 4 weeks of the previous injection. Medication coverage ratio (MCR) was calculated as the proportion of time a patient was covered by denosumab. Associations between pre-specified baseline covariates and 24-month persistence were assessed using multivariable logistic regression.

Results: The 24-month analyses included 1479 women (mean age 66.3-72.5 years) from 140 sites; persistence with denosumab was 75.1-86.0%, adherence 62.9-70.1%, and mean MCR 87.4-92.4%. No covariate had a significant effect on persistence across all four countries. For three countries, a recent fall decreased persistence; patients were generally older with chronic medical conditions. In some countries, other covariates (e.g., older age, comorbidity, immobility, and prescribing reasons) decreased persistence. Adverse drug reactions were reported in 2.3-6.9% patients.

Conclusions: Twenty-four-month persistence with denosumab is consistently high among postmenopausal women in Europe and may be influenced by patient characteristics. Further studies are needed to identify determinants of low persistence.

Keywords: Adherence; Compliance; Denosumab; Non-interventional study; Osteoporosis; Persistence.

Conflict of interest statement

AF-P is a principal investigator in studies sponsored by Amgen, Eli Lilly, and Servier Laboratories; has received unrestricted grants from Eli Lilly, Pfizer, and Roche; and has participated in speaker boards for Alexion, Amgen, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Meda, Novartis, Roche, and Servier Laboratories. NP has received research grants, consulting fees, and honoraria from Amgen, Eli Lilly, and Servier Laboratories. EG has received lecture fees from Amgen, Novartis, and Servier. MFT, CT, and LK-K are Amgen employees and shareholders. IF has received research funding from Amgen and Eli Lilly, and consultancy fees from Amgen. PG has received honoraria and research funding from Abbott, AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Pfizer, Procter and Gamble, Roche, and Will-Pharma. PM has received lecture fees from Amgen, Elpen, Genesis Pharma, Leo Pharma, Pfizer, UniPharma, and Vianex and research grants from Amgen. EB has no conflicts of interest to declare. JC has received honoraria from Amgen. ADA has received lecture fees from Amgen, Eli Lilly, Elpen, ITF Hellas, and Vianex. CN has received speaker honoraria, unrestricted educational grants, and research funding from Amgen, Eli Lilly, Merck Sharp & Dohme, Teva, and UCB Pharma. HR has received speaker honoraria from Amgen, Eli Lilly, Novartis, and Servier. PH has received honoraria and research funding from Amgen, Daiichi Sankyo, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Procter and Gamble, and Roche.

Figures

Fig. 1
Fig. 1
Study flow diagram. aSite excluded because sign-off on the Investigator Verification Page could not be obtained. Compared with the overall population, patients at the excluded site were of similar age; had fewer comorbidities; were taking fewer concomitant medications at baseline; had a lower incidence of historical fracture, prior fall, and discontinuation of prior postmenopausal osteoporosis therapy; had higher bone mineral density T-scores at total hip; and had less severe disease. bThis patient received one dose of denosumab and so was included in the SAS. FAS full analysis set, SAS safety analysis set
Fig. 2
Fig. 2
Persistence with and adherence to denosumab treatment at 24 months. Data are shown as percentages ±95% CIs. Persistence was defined as receiving the subsequent injection within 6 months + 8 weeks of the previous injection. Adherence was defined as administration of the subsequent injection within 6 months ± 4 weeks of the previous injection. CI confidence interval
Fig. 3
Fig. 3
Multivariable analysis of factors associated with 24-month persistence with denosumab treatment. *p ≤ 0.05. This graph has been cropped; arrows indicate where error bars exceed the axis limits. CI confidence interval, OR odds ratio, PMO postmenopausal osteoporosis

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