The association between prescription drugs and vaccines commonly prescribed to older people and bullous pemphigoid: a UK population-based study

Swiderski, Mikolaj; Vinogradova, Yana; Knaggs, Roger; Harman, Karen; Harwood, Rowan; Prasad, Vibhore; Persson, Monica Sm; Figueredo, Grazziela; Layfield, Carron; Gran, Sonia

Abstract

Introduction
Bullous pemphigoid (BP) is a serious skin disease that results in large painful blisters developing over the body and occurs most commonly in older people (over 70 years). Despite several comorbidities such as stroke and a threefold increase in mortality, BP remains under-researched. The cause of BP is unclear. The auto-immune process may be triggered by medicines such as diuretics, but current evidence mainly comprises case-reports and small hospital-based studies. Electronic healthcare records from the Clinical Practice Research Datalink (CPRD) provide an opportunity to conduct a large population-based study, representative of people with BP in the UK, to assess exposure to prescribed medicines. Early identification of BP and prompt withdrawal of suspect medicines may lead to BP remission and improve long-term patient outcomes, including quality of life. We aim to determine whether medicines/vaccines, prescribed for common conditions in older people, are associated with BP in the UK population. The objectives are:
i. To determine the adjusted odds ratio of developing BP per therapeutic group and class, and for multiple exposure (i.e. the use of more than one therapeutic group of medicine/vaccine during the observation period), for medicines/vaccines commonly prescribed to older people in the UK.
ii. To identify which of the above are less associated with risk of BP, giving clinicians/prescribers alternative treatment options.
iii. To identify additional medicines associated with BP using machine learning.
iv. To identify associations between combinations of medicines prescribed to BP patients using machine learning.
v. To describe patient characteristics of those at risk of BP, following medicine use, using machine learning.

Methods
A UK population-based nested case-control study using the CPRD to determine associations between identified medicines/vaccines and BP. BP cases will be matched to up to 4 controls (age, sex, GP practice) using incidence density sampling. Exposure: medicines/vaccines commonly prescribed for older people; antibacterial, medicine for the cardiovascular system, stroke, diabetes, dementia, and influenza vaccination in the year leading up to diagnosis. Outcome measures: the odds of BP per therapeutic group, per class, and individual medicine; (reference=no exposure). Analysis: multivariable conditional logistic regression adjusted for a priori confounders. Confounding by indication will be considered and different exposure criteria assessed. We will undertake exploratory association rule mining to identify individual and combinations of medicines prescribed prior to BP. We will conduct unsupervised machine learning cluster analysis to identify groups of patients with demographic and clinical characteristics and their associations with prescribed medicines linked to BP.

Discussion
This study will (i) provide greater awareness of the risk of drug-associated BP amongst specialist and non-specialist healthcare professionals and therefore may facilitate earlier diagnosis of BP; (ii) support withdrawal of suspect medicines and switching to alternatives, where available, to achieve earlier remission of BP.

Citation

Swiderski, M., Vinogradova, Y., Knaggs, R., Harman, K., Harwood, R., Prasad, V., …Gran, S. The association between prescription drugs and vaccines commonly prescribed to older people and bullous pemphigoid: a UK population-based study

• Working Paper Type: Working Paper
• Deposit Date: May 22, 2023
• Publicly Available Date: Jun 1, 2023
• Series Title: East Midlands Research into Ageing Network (EMRAN) Discussion Paper Series
• Series Number: 51
• Series ISSN: 2059-3341
• Keywords: Bullous pemphigoid, Pharmaco-epidemiology, Adverse drug reaction, Primary care
• Public URL: https://nottingham-repository.worktribe.com/output/20840681
• Publisher URL: https://doi.org/10.25878/3ybv-f758
• Related Public URLs: https://www.nottingham.ac.uk/emran/
• Additional Information: East Midlands Research into Ageing Network (EMRAN) is a research collaboration across the East Midlands to facilitate applied research into ageing and the care of older people.