Article

Association of low baseline levels of erythrocyte folate with treatment nonresponse at three months in rheumatoid arthritis patients receiving methotrexate.

Erasmus University Medical Center, Rotterdam, The Netherlands.
Arthritis & Rheumatology (Impact Factor: 7.48). 11/2013; 65(11):2803-13. DOI: 10.1002/art.38113
Source: PubMed

ABSTRACT 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).
A prospective derivation cohort (n = 285) and validation cohort (n = 102) of RA patients 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.
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.
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.

0 Bookmarks
 · 
75 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Stratified medicine approaches for the treatment of musculoskeletal disorders offer opportunities to effectively target interventions to those individuals who will gain most benefit from them and minimise adverse side effects. Such approaches have been the 'holy grail' of a variety of research fields spanning epidemiological, (epi)genetic, transcriptomic, proteomic and imaging biomarkers that predict disease diagnosis, prognosis or response to treatment. In this review, we highlight the successes and opportunities for stratified medicine approaches across a range of musculoskeletal disorders, with a focus on genetic risk factors, since these are the most stable across the lifetime of each individual.
    Current Opinion in Pharmacology 05/2014; 16C:127-132. DOI:10.1016/j.coph.2014.05.003 · 4.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Low-dose methotrexate (MTX) is the anchor drug in the treatment for rheumatoid arthritis (RA). Response to MTX is related to the intracellular MTX-polyglutamate (MTX-PG) levels and little is known about its determinants. We aimed to define the determinants of erythrocyte MTX-PG concentrations in 2 prospective cohorts of patients with RA.
    Annals of the Rheumatic Diseases 09/2014; DOI:10.3899/jrheum.131290 · 9.27 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Stratified medicine approaches for the treatment of musculoskeletal disorders offer opportunities to effectively target interventions to those individuals who will gain most benefit from them and minimise adverse side effects. Such approaches have been the ‘holy grail’ of a variety of research fields spanning epidemiological, (epi)genetic, transcriptomic, proteomic and imaging biomarkers that predict disease diagnosis, prognosis or response to treatment. In this review, we highlight the successes and opportunities for stratified medicine approaches across a range of musculoskeletal disorders, with a focus on genetic risk factors, since these are the most stable across the lifetime of each individual.
    Current Opinion in Pharmacology 01/2014; 16:127–132. · 4.23 Impact Factor

Full-text

Download
61 Downloads
Available from
May 31, 2014