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  Adverse Events to Methotrexate in Inflammatory Arthritis: Does Age Matter?

   Faculty of Biology, Medicine and Health

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  Dr Stephanie Shoop-Worrall, Prof K Hyrich, Dr S Verstappen  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

A consistent top-5 research priority for both children and adults with inflammatory arthritis is the tailoring of treatments to prevent or lessen adverse events. Adverse events from the gold-standard first-line treatment for inflammatory arthritis, methotrexate, can be extremely traumatic, ranging commonly from gastrointestinal toxicity to less common haematological events. In children, anticipatory nausea can persist for several days before drug administration, with drug-induced gastrointestinal side-effects persisting for 1-2 days after weekly doses of methotrexate. This leaves precious few days to either attend school, or develop social and recreational skills each week. In adults, ‘methotrexate fog’ can severely impair daily activities, including the ability to maintain social links, care for families and maintain consistent occupational work.

The ways methotrexate side-effects develop and cluster together is not well understood, particularly in the context of age. Anecdotally, it is thought that children are more susceptible to gastrointestinal methotrexate side effects than adults, but the mechanisms are currently unclear. Novel methods in artificial intelligence can uncover patterns of side effects, and determine how age and medication factors interact with these patterns. The understanding of age-related side effects could prompt tailoring of treatment for this inexpensive and often highly effective treatment, which is often discontinued and not restarted after initial side effects become intolerable.

Rich data on clinical and medication features, including adverse events have been collected as part of the UK JIA Treatment Registries (over n=1000 children and young people initiating methotrexate for the first time) and the Rheumatoid Arthritis Medication Study (over n=1000 adults initiating methotrexate for the first time). Highly detailed adverse event data have been recorded specifically for these studies.

Unsupervised machine learning approaches, such as latent profile analysis and group-based trajectory modelling, can be applied to these data to understand how adverse events cluster together over time and their relationship to age, disease types and medication factors. This can help understand disease mechanisms underpinning methotrexate side effects as well as develop tailored interventions to avoid or mitigate the impacts of these side effects.


Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in epidemiology, statistics, data science, computing or a relevant subject area. A Masters degree in a relevant subject and/or experience in a related subject area/discipline is desirable. Applicants with experience and training in epidemiology and also for those from a statistical or data science background are encouraged to apply.

Before you Apply 

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.  

How to Apply 

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website ( Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title - PhD Epidemiology.

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit

Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team [Email Address Removed]  

Equality, Diversity and Inclusion  

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website  

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Funding Notes

Applications are invited from self-funded students. This project has a Band 1 fee. Details of our different fee bands can be found on our website