Psoriasis is a chronic inflammatory disease causing red, scaly patches on the skin that may be itchy and painful.. Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting the skin and the joints. Ankylosing spondylitis (AS) is a chronic inflammatory arthritis, that primarily affects the joint It can cause pain and stiffness in peripheral joints, such as the joints of the hand.
Secukinumab (Cosentyx) is a recently approved drug used to treat psoriasis, PsA and AS. As part of the process of monitoring the safety of newly approved drugs, the manufacturer is required to provide regular reports to the health authorities who are responsible for drug regulation. These reports are called Periodic Safety Update Reports or PSURs.
Previous research suggests that patients with psoriasis, PsA and AS may have an increased risk of stroke or heart attack compared to the general population. In order to tell if secukinumab affects the rate of stroke or heart attack in these patients we need to determine what the rate of these events would be in the broad patient population.
This study will look at patients who have been diagnosed with these three conditions, determine the number who experience heart attacks, and strokes or who die as a result of heart attacks or strokes. These numbers will then be used in the PSUR reporting for secukinumab to determine if the drug is having any impact on the frequency of heart attacks, strokes and heart and stroke related deaths.
Objectives:
Population epidemiological studies suggest that patients with psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS) may have increased risk of cardiovascular and cerebrovascular disease compared with the general population of the same age and gender (Bengtsson et al., 2017, Keller et al., 2014, Szabo et al., 2011). Secukinumab (Cosentyx) is a recently approved drug developed to treat psoriasis, PsA and AS. To confirm whether Secukinumab affects the rate of stroke or heart attack in patients with these conditions we need to determine the background rates of these events in the disease population..
Periodic Safety Update Reports (PSURs) are reports submitted annually to Health Authorities to update the efficacy/effectiveness and safety profile of newly approved drugs.. The data from the Secukinumab clinical trials regarding important identified and potential risks are presented in these PSURs. Major adverse cardiovascular and cerebrovascular events (MACE) is one of the important potential risks, and as such it is important to contextualize the data obtained from the clinical trials, with background rates from the population with the disease.
We will use the Clinical Practice Research Datalink (CPRD) linked to national hospital episode statistics (HES) and mortality statistics (ONS) to estimate the rates of major adverse cardiovascular and cerebrovascular events (- or MACE) among the psoriasis, PsA and AS patient population.
Methods:
Incidence of MACE will be calculated as the number of new cases per 100 persons at risk (incidence proportion) and as the number of new cases per 1,000 person-years at risk (incidence rate). Confidence intervals for both incidence proportions and incidence rates will be computed. Incidence estimates with confidence intervals will be computed separately for each combination of age and sex.
Data analysis:
Patients recorded with diagnoses of psoriasis, PsA or AS between 1 January 1998 and 30 June 2017 (inclusive) will be used.
NB this ISAC corresponds to a re-run of the described analysis wherein which alterations have been made to the SAP. The resubmission of this ISAC was necessary as the original data was destroyed as per policy.
The outcome of interest in this analysis is any MACE, defined as a composite end-point of myocardial infarction, stroke and cardiovascular death. Read codes and ICD-10 codes for these events are provided in Appendix B.
Paola Primatesta - Chief Investigator - Novartis Pharma AG ( Switzerland )
Paul McGettigan - Corresponding Applicant - Novartis Ireland Limited
Brendan Lynch - Collaborator - Novartis Ireland Limited
Madison Brown - Collaborator - Novartis Ireland Limited
Shiwani Prasad - Collaborator - Novartis Healthcare (India) Pvt. Ltd.
Shreya Banerjee - Collaborator - Novartis Healthcare (India) Pvt. Ltd.
Sibasish Saha - Collaborator - Novartis Pharma AG ( Switzerland )
Valentine Jehl - Collaborator - Novartis Pharma AG ( Switzerland )
Ann Barber - Collaborator - Not from an Organisation
Brian Buckley - Collaborator - Novartis Pharmaceuticals UK Limited
Haijun Tian - Collaborator - Novartis Pharmaceuticals Corporation ( USA )
Martin McSharry - Collaborator - Optum
HES Accident and Emergency;HES Admitted Patient Care;ONS Death Registration Data