Enabling Stratified Medicine in Early Rheumatoid Arthritis

Predicting methotrexate (MTX) response and toxicity using an integrated polyomic response.

Project lead

This project is led by Professor Iain McInnes, Professor in Experimental Medicine at the University of Glasgow.

Background

Rheumatoid Arthritis (RA) is the commonest chronic inflammatory polyarthritis affecting ca 35 000 people in Scotland. There are ca 400 000 new cases in Europe and the US each year. With an emphasis on early diagnosis and intensive treatment, treatment options have improved in the last 20 years. However, RA stills attracts excess morbidity, mortality and societal burdens. In the U.K. the National Audit Office (NAO) estimates that RA costs the NHS ca £560 million p.a in health care costs with the majority of this in the acute sector and the additional costs of work-related disability are ca £1.8 bn p.a. Current RA drug treatment is dominated by methotrexate (MTX). Of the patients who are directed to MTX therapy, 30 % respond well, the remainder either fail to respond, have a sub-optimal response or suffer drug-related toxicity. Patients who fail to respond or achieve low remission are firstly directed to the combination of other disease modifying anti-rheumatic drugs (DMARDs) or subsequently to biological therapies.

The objective

The objective of this project was to test the hypothesis that MTX and toxicity can be usefully predicted by adopting an integrated polyomic approach for the development of predictive/clinical biomarker profiles.

Collaborators

Using SMS Innovation Platform, whole-genome DNA and RNA sequencing with support from bio-informaticians. The project will involve clinicians from NHS Greater Glasgow and Clyde and academic teams from the University of Glasgow.

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