Osteoporosis (OP) weakens bones, making them more likely to break (fracture). Romosozumab is a new medication used to treat patients at high risk of fractures (severe osteoporosis). Whilst effective at preventing further fractures in patients, there are concerns about the side effects of this drug, one of which is its effect on heart health. This application includes the UK assessment of how well physicians are following the guidelines set about who is fit to receive this drug. This study, combined with 2 other projects (assessing the effect on the heart and serious infection respectively), will use data from 7 countries in Europe to assess whether it is safe to use romosozumab in patients in clinical practice.
This project has two components. First, to assess the use of romosozumab and other osteoporosis medications over time. Second, to describe patients who use romosozumab and other osteoporosis medication and check that the romosozumab users meet the requirements for approved users of romosozumab, as defined by the European Medicines Agency. This study will be undertaken in all adults with at least 18 years of age.
The results of this study, along with the other two projects, will be sent to the European Medicines Agency, and based on the results, the continued availability of romosozumab in Europe and the UK may be affected.
Objective
The aim of this study is to evaluate adherence to the cardiovascular risk minimization measures (RMMs) for the use of romosozumab in the United Kingdom. To achieve this, utilization patterns, adherence to contraindications and target indications will be described amongst incident romosozumab users in routine clinical practice.
Specifically, the study objectives are:
1. Assess the prevalence and incidence of romosozumab use at the population level and the relative trends over time;
2. Characterize users of romosozumab, and to evaluate compliance with the EU approved indication and contraindication (history of MI or stroke) as per the RMMs
3. Describe prevalence and incidence of use of other OP medications, to characterize users and to provide context.
Population
The population is made of all adults in the UK registered in CPRD who are aged 18+ and have a specified gender.
Exposure
The exposure of interest is romosozumab. Comparator exposures are alendronate; other oral bisphosphonates; intravenous bisphosphonates; selective estrogen receptor modulators (SERMs); denosumab; and teriparatide.
Outcome
Outcomes come under 3 headings: population level measures including monthly prevalence and incidence of use, patient level measures including persistence and prevalence of contraindications amongst new users, and specific drug utilization measures for romosozumab users including compliance with RMMs and discontinuation.
Methods
Population-level measures: Monthly prevalence/incidence (and 95% Cis) of use overall per drug and after stratification will be estimated assuming a Poisson distribution. Secular trends/graphs will be plotted.
Patient-level: continuous outcomes will be reported as median (inter quartile range) and categorial outcomes will be reported as numbers and percentages (n[%]). Kaplan-Meier plots will depict persistence, whilst Sankey graphs will be plotted to illustrate treatment patterns/switching over time.
Characteristics of the different cohorts will be described for all potential covariates using quantitative measures (mean [SD], median [inter-quartile range]) or n(%) for each of the individual features.
Population level measures: monthly prevalence of use; monthly incidence of use
Patient level measures: duration of treatment/persistence; proportion persistent at 6, 12, 18 and 24 months; proportion switching treatment at 6, 12, 18 and 24 months; prevalence of contraindications amongst new romosozumab users; prevalence of documented indication amongst new romosozumab users.
Specific drug utilization measures for romosozumab users: compliance; discontinuation before 12 months.
Alireza Moayyeri - Chief Investigator - UCB Celltech
Annika Jodicke - Corresponding Applicant - University of Oxford
Antonella Delmestri - Collaborator - University of Oxford
Chao Lu - Collaborator - UCB BioSciences, Inc.
Daniel Prieto-Alhambra - Collaborator - University of Oxford
Eng Hooi Tan - Collaborator - University of Oxford
Maria Sanchez - Collaborator - University of Oxford
Victoria Y Strauss - Collaborator - University of Oxford
Alireza Moayyeri - Collaborator - UCB Celltech
Annika Jodicke - Collaborator - University of Oxford
John Logan - Collaborator - UCB Pharma SA - UK
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation