European non-interventional post-authorisation safety study (PASS) related to serious infections associated to romosozumab by the EU-ADR Alliance

Date of Approval
Application Number
20_000158
Technical Summary

Objective
The aim of this study is to characterise the risk of serious infections associated with the use of romosozumab, in comparison with other available osteoporosis medications in routine clinical practice in the UK as part of a study of 7 databases from Europe. This will be achieved by meeting three objectives: 1) assessing the incidence of serious infections in romosozumab patients and in patients using other osteoporosis medications; 2) assessing the incidence of serious infections in romosozumab users and amongst users of other osteoporosis medications, stratified by age, previous use of osteoporosis medications, and by prespecified key risk factors for serious infections; and 3) assess the comparative risk of serious infections between patients using romosozumab and alendronate.
Population
The population for this study is women aged 50+ with severe osteoporosis who are prescribed one of the below osteoporotic medications. Severe osteoporosis is identified by the presence of 1 or more fractures of any skeletal sites except face/skull/digit/s fractures recorded in the year prior to therapy initiation.
Exposure
The exposure of interest is romosozumab. Comparator exposures are alendronate (primary comparator); ibandronate (oral and intravenous), risedronate, zoledronate; denosumab; and teriparatide.
Outcome
The primary outcome of interest is serious infection leading to hospitalisation whilst the secondary outcome is death due to serious infection.
Methods
This will be designed using a cohort study with incidence rates of each outcome for each osteoporosis medication calculated using a Poisson model. Meanwhile, Cox proportional hazards with propensity score matching will be used for the comparative risk assessment. Multiple sensitivity analyses including negative control outcomes, self-controlled case series (SCCS), and instrumental variable analysis will be undertaken to assess the results for confounding.

Health Outcomes to be Measured

Primary: Serious infection leading to hospitalisation
Secondary: Death due to serious infection

Collaborators

Alireza Moayyeri - Chief Investigator - UCB Pharma SA - UK
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

Linkages

HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation