Studying cell behavior to predict individual responses to methotrexate treatment




Scientific study title:

Circulating extracellular vesicles in rheumatoid arthritis: Novel biomarkers of methotrexate treatment response



Principal Investigator:

Ines Colmegna, Associate Professor, Division of Rheumatology, Department of Medicine, McGill University. Scientist, Research Institute of the McGill University Health Sciences. Infectious Diseases and Immunity in Global Health Program.



Study Start Date:


Study End Date:



Why do this research?

In rheumatoid arthritis (RA), early diagnosis and rapid initiation of effective treatment are key to the control of symptoms associated with the disease and to reduce joint damage. Methotrexate (MTX) is the standard drug in the treatment of RA as it is effective, safe, affordable, and reduces complications associated with RA. For these reasons, methotrexate is recommended as the first line of treatment for recently diagnosed RA patients with moderate-to-high disease activity.

The real problem is that methotrexate alone is not enough to achieve arthritis control (i.e. disease remission) for all patients. In fact, 30-40% of RA patients will need other treatments besides or instead of MTX to control their disease. Having tests to determine which patients who will respond to methotrexate and those who would not, would be extremely useful to ensure that all RA patient get optimal treatment without delay.

Extracellular vesicles (EVs) are small packages of information released by all cells in our body in a very specific way. EVs allow cells to communicate between each other. There are different types of EVs that use the blood as a ‘highway’ to deliver their message. The value of studying EVs is such that they are considered as ‘liquid biopsies’ (i.e. liquid as we can obtain them from the blood, biopsies to highlight the huge amount of information that they provide similar to obtaining a tissue biopsy). In patients with breast cancer for example, studying EVs helps predict which patients would respond to certain chemotherapeutic drugs.



What will be done?

We propose that the study of EVs at the time of RA diagnosis could help define the patients who would benefit from methotrexate versus other treatment. To test this, we propose three aims:

1- Define in vitro, the types of EVs secreted by immune cells before and after they are treated with methotrexate.
2- Optimize methods to study blood (plasma) derived EVs.
3- Describe the features of EVs in the blood of RA patients who responded or not to MTX treatment.

This work can be transformative for the care of RA patients as it has the potential to:

1- Distinguish between people that would respond or not to methotrexate using a non-invasive approach (blood test)
2- Optimize the treatment of RA patients by providing the ‘best treatment for the right person.’
3- Uncover a new mechanism of action (EV production) of methotrexate that can help find new drugs with similar effects.



Who is involved?

This is a pilot project, testing a small scale version to understand possible results of a full-scale version. We will recruit 10 RA patients from a single clinic who are interested in providing blood samples before and after starting methotrexate treatment.



Co- Investigators

Marie Hudson, MD, MPH, FRCPC, Associated Professor, Department of Medicine, McGill University



Funding Agency

The Arthritis Society