Trial reportArthritis research & therapy2019
Higher baseline global leukocyte DNA methylation is associated with MTX non-response in early RA patients.
Trial report in Arthritis research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Review
- Transposable elements as a possible missing link between genetic predisposition and environmental triggers of autoimmune disorders: insights from type 1 diabetes, systemic lupus erythematosus and rheumatoid arthritis.Frontiers in immunology · 2026Review
- The Type I Interferon Axis in Systemic Autoimmune Diseases: From Molecular Pathways to Targeted Therapy.Biomolecules · 2025Review
- Comprehensive Parent-Metabolite PBPK/PD Modeling Insights Into Methotrexate Personalized Dosing Strategies in Patients With Rheumatoid Arthritis.CPT: pharmacometrics & systems pharmacology · 2025Article
- DNA methylation in human diseases.Heliyon · 2024Review
- Role of IFN-α in Rheumatoid Arthritis.Current rheumatology reports · 2024Review
- Autoimmune disease: a view of epigenetics and therapeutic targeting.Frontiers in immunology · 2024Review
- Towards Personalized Medicine in Rheumatoid Arthritis.Open access rheumatology : research and reviews · 2024Review
- Micronutrient regulation of the DNA methylome.Frontiers in epigenetics and epigenomics · 2024Review
- DNA Methylation Signatures of Response to Conventional Synthetic and Biologic Disease-Modifying Antirheumatic Drugs (DMARDs) in Rheumatoid Arthritis.Biomedicines · 2023Review
- Identification of Cell-Specific Differential DNA Methylation Associated With Methotrexate Treatment Response in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- The prognostic value of whole-genome DNA methylation in response to Leflunomide in patients with Rheumatoid Arthritis.Frontiers in immunology · 2023Article
- Novel DNA methylome biomarkers associated with adalimumab response in rheumatoid arthritis patients.Frontiers in immunology · 2023Article
- Article
- -Omic Approaches and Treatment Response in Rheumatoid Arthritis.Pharmaceutics · 2022Review
- Article
- Cell-Free DNA in Rheumatoid Arthritis.International journal of molecular sciences · 2021Review
- Complex Machine-Learning Algorithms and Multivariable Logistic Regression on Par in the Prediction of Insufficient Clinical Response to Methotrexate in Rheumatoid Arthritis.Journal of personalized medicine · 2021Article
- Global DNA (hydroxy)methylation is stable over time under several storage conditions and temperatures.Epigenetics · 2021Article
- Epigenome wide association study of response to methotrexate in early rheumatoid arthritis patients.PloS one · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLow-dose methotrexate (MTX) is the first-line therapy in early rheumatoid arthritis (eRA). Up to 40% of eRA patients do not benefit from MTX therapy. MTX has been shown to inhibit one-carbon metabolism, which is involved in the donation of methyl groups. In this study, we investigate baseline global DNA methylation and changes in DNA methylation during treatment in relation to clinical non-response after 3 months of MTX treatment.
methodsTwo hundred ninety-four blood samples were collected from the Treatment in the Rotterdam Early Arthritis Cohort (tREACH, ISRCTN26791028), a multicenter, stratified single-blind clinical trial of eRA patients. Global DNA (hydroxy)methylation was quantified using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) and validated with a global DNA LINE-1 methylation technique. MTX response was determined as ΔDAS28. Additionally, patients were stratified into two response groups according to the European League Against Rheumatism (EULAR) response criteria. Associations between global DNA methylation and response were examined using univariate regression models adjusted for baseline DAS28, baseline erythrocyte folate levels, and body mass index (BMI).
resultsHigher baseline global DNA methylation was associated with less decrease of DAS28 (β = 0.15, p = 0.013) and with MTX non-response (OR = 0.010, 95% CI = 0.001-0.188). This result was validated in LINE-1 elements (β = 0.22, p = 0.026). Changes in global DNA (hydroxy)methylation were not associated with MTX response over 3 months.
conclusionsThese results show that higher baseline global DNA methylation in treatment naïve eRA patients is associated with decreased clinical response after 3 months of treatment of eRA patients and can be further evaluated as a predictor for MTX therapy non-response.
trial registrationISRCTN, ISRCTN26791028 , registered 23 August 2007-retrospectively registered.
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