Galcanezumab is a new drug to prevent migraine headache, a disabling condition accompanied by moderate to severe (throbbing, pounding, pulsating) head pain, nausea and/or vomiting, sensitivity to light, noise and/or smell which lasts from several hours to several days. Galcanezumab has recently been licenced in the UK, Europe and other countries. This study aims to describe and understand the use of galcanezumab in the general population, as well as in special populations of interest such as the elderly or individuals with previous heart or blood vessel disease. These special populations were excluded from the clinical trials conducted before galcanezumab came on the market. Therefore, it is important to learn more about the safety of galcanezumab in these populations.
The study aims to describe the population using glacanezumab with regard to patient characteristics, as well as to assess the occurrence of serious hypersensitivity reactions (undesirable and exaggerated or inappropriate reactions by the immune system), tumour growth or serious undesirable heart and blood vessel events associated with the use of galcanezumab. For comparison reasons, the frequency of serious hypersensitivity reactions, tumour growth and serious heart and blood vessel events will also be assessed in patients using topiramate, another drug which is also used for migraine prevention.
The public will benefit from this study, because to date information about the safety of glacanezumab in patients with recent heart or blood vessel disease as well as patients aged 65 years or more (who were excluded from the clinical trial population) is scarce.
Galcanezumab is a humanised monoclonal antibody indicated for migraine prophylaxis in adults with at least four migraine days per month.
This is a Post-Authorization Safety Study, the primary objective of which is to evaluate galcanezumab use in all exposed patients ≥18 years and in special populations (i.e., patients with recent acute cardiovascular (CV) events and/or serious CV risk, as well as patients > 65 years). The secondary objective is to assess the incidence of serious hypersensitivity reactions, malignancy and serious CV events in users of galcanezumab, and to compare the incidence of serious hypersensitivity reactions, malignancy and CV events between users of galcanezumab and users of the comparator drug topiramate.
This will be a cohort study starting at the galcanezumab approval date in the EU/UK (14 Nov 2018) and end on 31 December 2025.It will comprise all patients with a recorded prescription for galcanezumab in CPRD Aurum, and a comparator cohort of exact, and separately, propensity score matched topiramate users. Cohort entry will be the date of their first recorded prescription for galcanezumab or topiramate in the comparator cohort. Baseline and treatment characteristics of the galcanezumab users will be described.
We will estimate crude incidence rates for each outcome of interest (using Hospital Episode Statistics admission data to determine the outcomes serious CV events and serious hypersensitivity reactions) and we will calculate hazard ratios (and 95% CIs) for serious CV events and malignancy outcomes using Cox proportional hazards regression comparing galcanezumab users to topiramate users. Several sensitivity analyses will be conducted to evaluate the robustness of the findings.
The results of the study will benefit patients and doctors with migraine by adding knowledge about the safety of galcanezumab and its potential adverse effects compared with a standard antimigraine drug (i.e. topiramate).
Number and characteristics of galcanezumab users; incidence of serious CV events (Appendix C), serious hypersensitivity reactions (Appendix D), and malignancies (Appendix E)
Patient characteristics including age, sex, calendar year of cohort entry, available database history and - follow-up (stratified by calendar year of cohort entry) (i.e. time from index date until the last date of follow-up available in the database, the study end date, or death, whichever occurs first), reason for end of database follow-up (end of data collection, end of study period, deceased), reason for end of time at risk for the outcome serious CV event, duration of available database follow-up by reason for end of time at risk for the outcome serious CV event, medication history: Antimigraine preparations (e.g. ergotamine, triptans, CGRP antagonists), biologics, opioids, non-steroidal anti-inflammatory drugs (NSAIDs) (limited to prescribed medication only), antidepressants, botulinum toxin, CV medication (categorised, e.g. beta-blockers, ACE inhibitors), history of serious CV events (myocardial infarction (MI), transient ischaemic stroke (TIA), ischaemic stroke, ischaemic heart disease, angina pectoris (AP), percutaneous coronary intervention (PCI), coronary revascularisation), history of serious hypersensitivity reactions,
CV risk factors (smoking status, BMI, hypertension, hyperlipidaemia, Type 2 diabetes mellitus, impaired renal function, history of haemorrhagic stroke),
comorbidities (psychiatric disorders, heart failure, peripheral vascular disease), days of supply for acute migraine medication, traceable start of migraine, length of migraine disease, healthcare utilisation measures (e.g. number of drugs, hospitalisations)
Serious CV events including hospitalisation for: MI, TIA, ischaemic stroke, ischaemic heart disease, unstable AP, PCI, coronary revascularisation and CV death. Serious CV events will be reported as composite and individual outcomes.
Serious hypersensitivity reactions defined as hospitalisation for anaphylaxis or allergy, hospitalisations or emergency care visits for angioedema, acute asthma or acute bronchospasm, acute upper airway obstruction, epinephrine administration and death from serious hypersensitivity reactions (i.e. death after any of these events) will additionally be assessed as part of this outcome
Malignancies including a diagnosis of any cancer, excluding non-melanoma skin cancer (NMSC). Malignancies will be reported as a composite outcome (all malignancies, excluding NMSC), and by type of the first malignancy (i.e. per primary cancer site).
Susan Jick - Chief Investigator - BCDSP - Boston Collaborative Drug Surveillance Program
Claudia Becker - Corresponding Applicant - University of Basel
Christoph Meier - Collaborator - University of Basel
HES Admitted Patient Care;ONS Death Registration Data