COMPLETED: Medicines optimisation
Principal Investigator: Dr Simon Fraser
Team members: Dr Simon Fraser (Associate Professor of Public Health. School of Primary Care and Population Sciences, Faculty of Medicine, Southampton General Hospital), Professor Chris Edwards (Professor of Rheumatology, Southampton and Associate Director of the NIHR Clinical Research Facility) Dr Chris Holroyd (Consultant Rheumatologist, University Hospital Southampton NHS Foundation Trust), Dr Kinda Ibrahim (Senior Research Fellow, Faculty of Medicine, University Hospital Southampton NHS Foundation Trust), Dr Ravina Barrett (Pharmacist, University of Portsmouth), Dr Clare Howard (Chief Pharmacist, Medicines Optimisation, Wessex AHSN), Dr Mary O’Brien (NHS England, NHS Rightcare), Dr David Culliford (Senior Medical Statistician, Health Sciences, University of Southampton), Professor Paul Roderick (Professor of Public Health, Primary Care and Population Sciences, University of Southampton), Professor James Batchelor (Director Clinical Informatics Research Unit, Faculty of Medicine, University of Southampton), Dr Matthew Stammers (Senior Endoscopy Fellow, University Hospital Southampton and Clinical Informatics Research Fellow at Clinical Informatics Research Unit)
Start: 1 October 2019
Ends: 30 September 2024
Project Partners: University Hospital Southampton NHS Foundation Trust, NHS England (NHS Rightcare), University of Portsmouth, University of Southampton, Academic Health Sciences Network (AHSN) Wessex.
Lay summaryPainful conditions associated with age (such as arthritis) are common in the UK and safe pain relief options for older people are limited. Anti-inflammatory drugs such as ibuprofen are widely used – both bought from the pharmacy and prescribed by doctors, but they have significant risks, such as bleeding from the stomach and kidney damage. Older people and those with certain long-term medical conditions are at higher risk of experiencing bad effects from these drugs.
Another issue concerns people who are taking one of a group of medications call ‘disease-modifying anti-rheumatic drugs’ (DMARDs). These drugs are often used for rheumatoid arthritis and work by slowing its progression, reducing the likelihood of severe joint damage and other related health problems. They are also used for inflammatory bowel diseases, such as Crohn’s disease. Methotrexate is one of the most commonly used DMARD in arthritis and azathioprine is one of the most commonly used in inflammatory bowel disease. Anti-TNF drugs are an important group of so called ‘biological agents’ – another type of DMARD.
DMARDs are powerful drugs that require regular blood tests to check for adverse effects, such as liver problems, and guidelines advise how often these tests should be done. However, for most people, these blood tests are almost never abnormal, and could potentially be safely done less frequently. In addition, some people with inflammatory arthritis have an excellent response to DMARDs. Stopping DMARDs can lead to flare ups of disease, but the amount of therapy used may be tapered successfully to reduce dose-dependent adverse events and costs.
In one part of this research we will use an anonymous database of about half a million people from GP practices in Hampshire to identify how many people are prescribed anti-inflammatory drugs, particularly those who may be at high risk of complications by being older or having other conditions. The aim is to help doctors transfer high risk patients to other pain relief options.
In another part, we will use the same dataset and also data from people who have attended University Hospital Southampton NHS Foundation Trust who take methotrexate, azathioprine and anti-TNF drugs. We will look at their blood results to see if some people might not need blood tests so frequently. Patients may be understandably nervous that problems could be missed if the blood check is not done so often, so we plan future research asking patients and doctors whether such reduction in checks would be acceptable.
We will also investigate the possibility of successful dose reduction strategies for anti-TNF drugs. Specifically, we will identify which kinds of patients tend to succeed in being able to reduce the dose.
This research has potential to reduce the burden on patients and on the NHS by reducing the frequency of blood tests and/or medication burden for some people and avoiding hospital admissions for anti-inflammatory drug complications.
Through connections our team has already, the results of this research will be shared with relevant doctors, nurses and patient groups across Wessex so it makes a difference locally. It will also be published in academic journals and presented at conferences.
What did we learn?
In the two different parts of the project we found that:
About half of people taking the ‘disease modifying’ drugs (‘DMARDs’) methotrexate for rheumatoid arthritis or azathioprine for inflammatory bowel disease experienced no blood test abnormality over two years despite having to have blood tests every three months. Reducing testing frequency may therefore be safe for younger people and those without other long-term conditions.
Among people taking non-steroidal anti-inflammatory drugs (‘NSAIDs’ like ibuprofen) the risk of kidney damage was highest among older people with combinations of long-term conditions including chronic kidney disease, diabetes, heart disease and heart failure, and high blood pressure. These people should avoid taking NSAIDs and we provided a way for GPs to identify them in their databases.
What difference will this new knowledge make?
DMARDs: Further investigation is needed on the safety and acceptability of reduced blood testing frequency testing for some people taking DMARDs but this could potentially result in reduced unnecessary patient anxiety and burden, fewer referrals to hospital and reduce resource use for the NHS.
If testing could be reduced this would mean reduced treatment burden for patients and reduced cost and admin work for the NHS
NSAIDs: GP practices can be provided with a search tool that helps identify those at highest risk of kidney damage from NSAIDs. Using this information they can review and stop NSAIDs to reduce the risk.
If prescribing was stopped for some people at risk, this would reduce risk of acute kidney injury which can have lasting consequences or even be fatal
What's next?
DMARDs:
Our study informed further work on the risk stratification of people taking DMARDs in this paper: https://www.bmj.com/content/381/bmj-2022-074678?ijkey=19f0b9a96fd3e38092eb855e24fd903f7e3fec2f&keytype2=tf_ipsecsha
and was cited in this paper about supporting sustainability through reduced testing:
https://www.bmj.com/content/382/bmj.p1645
Tom Lewis, consultant pathologist and co-national lead pathology ‘Getting It Right First Time’ programme strongly supported this work
NSAIDs:
We searched the entire Dorset intelligence and insight Service (DiiS) database (over 800,000 people) using our risk tool to identify the variation in NSAID prescribing by practice and risk of acute kidney injury
We ran an NSAID masterclass with people from over 50 GP practices in Dorset to share this information, to teach about NSAID use and to share our method to identify those at risk in practices.
Publications:
Persistently normal blood tests in patients taking methotrexate for RA or azathioprine for IBD: a retrospective cohort study | British Journal of General Practice (bjgp.org)