OBJECTIVE: To investigate whether baseline concentrations of one-carbon metabolism biomarkers are associated with treatment nonresponse and adverse events in rheumatoid arthritis (RA) patients receivingmethotrexate (MTX). METHODS:A prospective derivation cohort (n = 285) and validation cohort (n = 102) of RA patients receivingMTX were studied. Concentrations of plasma homocysteine, serum vitamin B12 , serum folate, erythrocyte vitamin B6 , 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 were assessed using biochemical parameters and health status questionnaires. Analyses were corrected for baseline DAS28, age, sex, MTX dose, comedications, and presence of the methylenetetrahydrofolate reductase 677TT genotype. RESULTS: In 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 (β = -0.15, P = 0.037) and the validation cohort (β = -0.20, P = 0.048). In line with these results, lower baseline erythrocyte folate levels were linearly associated with a 3-month DAS28 of >3.2 in both cohorts (derivation cohort, P = 0.049; validation cohort, P = 0.021) and with nonresponse according to the EULAR criteria (derivation cohort, P = 0.066; validation cohort, P = 0.027). None of the other biomarkers (levels at baseline or changes over 3 months) were associated with the DAS28 or treatment nonresponse. Baseline levels of the biomarkers and changes in levels after 3 months were not associated with incidence of adverse events. CONCLUSION: A 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.
RCT Entities:
OBJECTIVE: To 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). METHODS: A prospective derivation cohort (n = 285) and validation cohort (n = 102) of RApatients receiving MTX were studied. Concentrations of plasma homocysteine, serum vitamin B12 , serum folate, erythrocyte vitamin B6 , 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 were assessed using biochemical parameters and health status questionnaires. Analyses were corrected for baseline DAS28, age, sex, MTX dose, comedications, and presence of the methylenetetrahydrofolate reductase 677TT genotype. RESULTS: In 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 (β = -0.15, P = 0.037) and the validation cohort (β = -0.20, P = 0.048). In line with these results, lower baseline erythrocyte folate levels were linearly associated with a 3-month DAS28 of >3.2 in both cohorts (derivation cohort, P = 0.049; validation cohort, P = 0.021) and with nonresponse according to the EULAR criteria (derivation cohort, P = 0.066; validation cohort, P = 0.027). None of the other biomarkers (levels at baseline or changes over 3 months) were associated with the DAS28 or treatment nonresponse. Baseline levels of the biomarkers and changes in levels after 3 months were not associated with incidence of adverse events. CONCLUSION: A 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.
Authors: M A H den Hoed; E Lopez-Lopez; M L te Winkel; W Tissing; J D E de Rooij; A Gutierrez-Camino; A Garcia-Orad; E den Boer; R Pieters; S M F Pluijm; R de Jonge; M M van den Heuvel-Eibrink Journal: Pharmacogenomics J Date: 2014-11-04 Impact factor: 3.550
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Authors: Helen R Gosselt; Maxime M A Verhoeven; Maurits C F J de Rotte; Saskia M F Pluijm; Ittai B Muller; Gerrit Jansen; Janneke Tekstra; Maja Bulatović-Ćalasan; Sandra G Heil; Floris P J G Lafeber; Johanna M W Hazes; Robert de Jonge Journal: Rheumatol Ther Date: 2020-09-14