Association of Low Baseline Levels of Erythrocyte Folate With Treatment Nonresponse at Three Months in Rheumatoid Arthritis Patients Receiving Methotrexate

ObjectiveTo investigate whether baseline concentrations of one-carbon metabolism biomarkers are associated with treatment nonresponse and adverse events in rheumatoid arthritis (RA) patients receiving methotrexate (MTX). MethodsA prospective derivation cohort (n = 285) and validation cohort (n = 102) of RA patients receiving MTX were studied. Concentrations of plasma homocysteine, serum vitamin B-12, serum folate, erythrocyte vitamin B-6, and erythrocyte folate were determined at baseline and after 3 months of treatment. Nonresponse after 3 months was assessed using the Disease Activity Score in 28 joints (DAS28) and the European League Against Rheumatism (EULAR) response criteria. Adverse events at 3 months wer ResultsIn the derivation cohort, the mean DAS28 scores at baseline and 3 months were 4.94 and 3.12, respectively, and 78% of patients experienced adverse events. This was similar between the 2 cohorts, despite a lower MTX dose in the validation cohort. Patients with lower levels of erythrocyte folate at baseline had a higher DAS28 at 3 months in both the derivation cohort ( = -0.15, P = 0.037) and the validation cohort ( = -0.20, P = 0.048). In line with these results, lower baseline erythrocyte ConclusionA low baseline concentration of erythrocyte folate is associated with high disease activity and nonresponse at 3 months after the start of MTX treatment and could be used in prediction models for MTX outcome. None of the investigated one-carbon metabolism biomarkers were associated with incidence of adverse events at 3 months.