BRU researchers lead pilot MRC-NIHR National Phenome Centre study to profile methotrexate response in Rheumatoid Arthritis

The NIHR Manchester Musculoskeletal Biomedical Research Unit (BRU) has been awarded an MRC-NIHR National Phenome Centre pilot project, which will facilitate new and exciting research into identifying biomarkers that could predict Rheumatoid Arthritis (RA) patients’ response to methotrexate (MTX).

Currently MTX is recommended as the first-line therapy for patients with RA; however only 55% of patients remain on this inexpensive drug beyond two years after initiation of treatment. The figure suggests that many patients on MTX show limited or no response to this agent, or experience adverse effects that necessitate its discontinuation.

With the support of the MRC-NIHR National Phenome Centre, Professor of Rheumatology and BRU Theme Lead Anne Barton and BRU Research Fellow, Dr Darren Plant, will lead BRU researchers to investigate metabolic predictors of response to MTX. The aim of this work is to identify pre-treatment biomarkers that can be predictive of an RA patient’s future response to MTX treatment.

The study will collect detailed clinical information and blood samples, to permit extraction of DNA, RNA and serum from 140 RA patients taking part in the Rheumatoid Arthritis Medication Study (RAMS), who are about to start MTX for the first time. Initially, serum measurements from European League Against Rheumatism (EULAR) good responders will be compared to non-responders. EULAR response criteria classifies individual patients as non-, moderate, or good responders, dependent on the extent of change in the level of disease activity achieved in response to treatment.

Once the samples have been collected researchers will work with the Phenome Centre to perform metabolite profiling in serum samples. The systematic study of metabolites will provide a unique view of the cellular processes that potentially influence MTX response.

If researchers are successful in identifying biomarkers in this pilot study, a full-scale study is planned to validate the biomarkers found.

Professor Barton explains:

Response to therapy is likely to be multifactorial. In the future we plan to include these metabolite data in a multi-omics analysis, which will also include data derived from DNA and RNA. That will allow us to better define the biological basis of response to MTX, which is still our best first-line treatment for patients with RA.

Findings from this and future research will allow researchers to develop a classification decision system, which will provide clinicians with a factually driven decision tool for use in clinical practice, to evaluate whether a patient will respond well to MTX based on a number of factors.

All BRU research is driven by the aim of treating arthritis right first time and providing better care for patients. By predicting which patients will response well to MTX and which patients won’t, it will not only bring efficiencies to the NHS but provide better disease management and effective treatments for RA patients.