Low Folate Levels Tied to Poor Methotrexate Response in RA


Measuring folate in red blood cells before methotrexate treatment for rheumatoid arthritis may be a good way to select patients least likely to require expensive biologics.

de Rotte MCFJ, de Jong PHP, Pluijm SMF, et al. Low baseline folate in erythrocytes is associated with non-response in rheumatoid arthritis patients on methotrexate. Arthritis & Rheumatism (2013) Published online October 8, 2013. DOI: 10.1002/art.38113.

Rheumatoid arthritis (RA) patients starting methotrexate (MTX) therapy with low folate in their red blood cells are less likely to respond to treatment – and still have active disease after three months, according to Dutch researchers.

Three months marks the time clinicians typically decide to stop or change RA therapy, often to biologics. The researchers suggest erythrocyte-folate levels may act as a predictor of treatment response – helping to distinguish patients who may be better off with biologics and sparing others the often considerable cost.

Data from two independent prospective studies of RA patients show that a lower pre-treatment erythrocyte-folate level (≤1,000 nmol/L) is linked to high 28-joint disease activity (DAS28 >3.2) and lower red blood cell concentrations of MTX at three months.

Women in their 50s make up the two patient populations: A derivation cohort meeting 2010 ACR criteria for RA (n=285) and a validation cohort of physician-diagnosed patients (n=102).

Patients with low baseline intracellular folate may have less ability to absorb and use methotrexate, the researchers explain. MTX is a folate antagonist that is structurally similar to the B-vitamin and uses the same metabolic pathway.

Greater disease activity is seen at three months in low erythrocyte-folate patients, even factoring in differences in methotrexate dose and concurrent use of other disease modifying antirheumatic drugs.

While both cohorts took 10 mg of folic acid weekly with MTX and co-medications during the study, folate supplementation did not appear to affect treatment response, the researchers point out.

Adverse events – mostly gastrointestinal complaints and malaise – are similar (around 78%) in both groups.


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