Polymyalgia rheumatica is an illness affecting older adults. It causes pain and stiffness around the shoulders and hips and can affect people’s ability to do everyday activities. The main treatment is steroid tablets (prednisolone), which need to be taken for around two years but sometimes longer.
Prednisolone can cause side-effects including increasing the chances of people breaking bones and bleeding from the gut. People with polymyalgia rheumatica have told researchers that understanding more about the side-effects of steroids and how to prevent them is important. Some medicines given to treat pain in polymyalgia rheumatica also increase the chances of bone and gut problems. There are other medicines that can be given to reduce the chances of these side-effects happening (called “preventative medicines”), but low numbers of people receive these.
Using information from people’s anonymous primary care medical records, linked to data from hospital admissions and local area deprivation data, we will find out:
- the effect of preventative medicines on the chances of having fractures / gut side-effects
- what the effect on the health of people with polymyalgia rheumatica, as a group, would be if preventative medicines were prescribed in the way guidelines suggest.
We will discuss the findings with our study patient group to ensure we produce information that is helpful to people with polymyalgia rheumatica and healthcare staff that care for them. This study will help us to better treat people diagnosed with polymyalgia rheumatica.
Polymyalgia rheumatica (PMR) causes pain, stiffness, and disability in older adults. It typically responds rapidly to glucocorticoids (GCs) with the dose being tapered over 2-3 years.
Two risks associated with GCs are an increased rate of fractures and serious gastrointestinal (GI) adverse events. Pharmacological strategies to reduce the risk of complications exist, but studies show that prescribing of prophylactic medication is low. Additionally, analgesia used to manage pain in PMR can contribute to risks of fractures and GI adverse events. We will conduct two emulated “target trials” to look at the effect of prescribing prophylactic 1) bisphosphonates and 2) gastro-protective medications on incidence of 1) fracture and 2) GI adverse effects, respectively. This study will use CPRD Aurum primary care data, linked Hospital Episode Statistics Admitted Patient Care Data (HES APC, to improve outcome ascertainment) and indices of multiple deprivation quintiles (to adjust for levels of deprivation).
A retrospective cohort of people with incident PMR treated with GCs (January 2010 and March 2022) will be formed in CPRD Aurum. Date of steroid prescription will be the time zero for the emulated trial. Those with a prescription for 1) an oral bisphosphonate; or 2) gastro-protective medicines before time zero will be excluded. Outcomes will be 1) fragility fractures and 2) GI bleeding, defined in Aurum and HES APC. We will estimate causal average treatment effects (with 95% confidence intervals and p-values) on the outcomes at 1 year after time zero of being treated compared to not being treated, using targeted maximum likelihood estimation (for example, using R package ltmle), with 1-month time intervals, and time-varying treatments and confounders.
Findings will be discussed with our study patient group to ensure we produce outputs helpful to both patients and clinicians and thus impact meaningfully on the future treatment of people diagnosed with PMR.
Fragility fractures; Gastrointestinal adverse events (peptic ulcer disease and upper gastrointestinal bleeds)
Helen Twohig - Chief Investigator - Keele University
David Jenkinson - Corresponding Applicant - Keele University
Ian Scott - Collaborator - Keele University
James Bailey - Collaborator - Keele University
Samantha Hider - Collaborator - Keele University
Sara Muller - Collaborator - Keele University
HES Admitted Patient Care;Patient Level Index of Multiple Deprivation