Development and validation of a methotrexate adherence assay

by | Jun 6, 2019 | Rheumatoid arthritis | 0 comments

Rheumatoid Arthritis (RA) affects nearly 1% of people in Britain. Most patients with RA experience joint pain, stiffness and swelling. This is due to inflammation of the joints that can lead to joint damage. RA can have a severe impact on the lives of sufferers.

RA treatment follows a standard pathway. Anti-rheumatic drugs, such as methotrexate are used first. If patients have persistent disease despite this, they may be prescribed “biologic” anti-rheumatics. These are more expensive, but are usually more effective in those whose joint inflammation doesn’t improve on methotrexate alone.

None of the treatments work for everyone.  Time on ineffective medication, where the disease remains active, contributes to joint damage and disability. One of the major influences on whether or not a drug works is “adherence”. This is whether or not a patient is taking their medications as prescribed. Non-adherence to treatments costs the NHS £500 million per year. As RA is estimated to cost the NHS over £8 billion per year, improving adherence could result in huge health and economic benefits.

Research has shown that up to 40% of patients are non-adherent to methotrexate treatment. This non-adherence is associated with reduced drug response. Prescribers in the NHS are currently unable to test if a patient is adherent, preventing targeted patient support that would help to improve adherence.

The aim of this study was to develop and test the ability of a new blood test to accurately measure methotrexate adherence.  First, we used the new blood test to measure the amount of methotrexate in the blood of 20 patients with RA over a 6 day period. Using these results we optimised the blood test to make the results as sensitive as possible.

Next, samples from patients taking part in the Rheumatoid Arthritis Medications Study were tested for methotrexate adherence. This is a UK-based study of patients with RA. It is designed to identify factors indicating that a positive response to methotrexate treatment is more likely. Patients recorded when they last took their methotrexate and a blood sample was taken which was tested for adherence to methotrexate.

Seven out of the 138 samples we tested showed non-adherence. This was where the patient recorded in the diary that they had taken their methotrexate correctly, but the test showed lower levels of methotrexate in the blood than expected. This suggests the test has a 95% sensitivity to detect non-adherence.

In conclusion, this research project showed that methotrexate adherence can be measured using the developed blood test. The next step in the development of the blood test is to explore whether measuring methotrexate adherence and providing patient support to improve adherence where required, can improve treatment response.


Bluett, J. et al. Development and validation of a methotrexate adherence assay. Annals of the Rheumatic Diseases, 5 June 2019 [E-pub Ahead of Print]  DOI:10.1136/annrheumdis-2019-215446 | Publication link: 66ebd3ea-f2c8-4cef-b156-5839a4a6c8d6