Observational studyRheumatology (Oxford, England)2020
Differential DNA methylation correlates with response to methotrexate in rheumatoid arthritis.
Observational study in Rheumatology (Oxford, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic Review and Meta-analysis of Peripheral Blood DNA Methylation Studies in Inflammatory Bowel Disease.Journal of Crohn's & colitis · 2023Pooled it
- Dysregulation of the DNA repair‑immune axis: Targeted therapeutic strategies for autoimmune diseases (Review).International journal of molecular medicine · 2026Review
- Epigenetic dysregulation of B‑cells in autoimmune diseases and lymphomas (Review).International journal of molecular medicine · 2026Review
- Review
- The Type I Interferon Axis in Systemic Autoimmune Diseases: From Molecular Pathways to Targeted Therapy.Biomolecules · 2025Review
- A Longitudinal Study Reveals Metabolomic Markers for Individuals at Risk, Disease Severity, and Treatment Response in Rheumatoid Arthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Therapeutic gene targets and epigenetic modifications in rheumatoid arthritis: Insights from MTX, JAK inhibitors, and LLDT-8.Biochemistry and biophysics reports · 2025Article
- DNA and RNA Methylation in Rheumatoid Arthritis-A Narrative Review.Epigenomes · 2025Review
- The interaction between a leflunomide-response methylation site (cg17330251) and variant (rs705379) on response to leflunomide in patients with rheumatoid arthritis.Frontiers in pharmacology · 2025Article
- A holistic approach to understanding immune-mediated inflammatory diseases: bioinformatic tools to integrate omics data.Computational and structural biotechnology journal · 2024Review
- Whole Blood DNA Methylation Changes Are Associated with Anti-TNF Drug Concentration in Patients with Crohn's Disease.Journal of Crohn's & colitis · 2024Article
- Micro-RNA content of circulating extracellular vesicles in early rheumatoid arthritis as biomarkers and mediators of methotrexate efficacy.Rheumatology (Oxford, England) · 2024Article
- DNA methylation in human diseases.Heliyon · 2024Review
- Role of IFN-α in Rheumatoid Arthritis.Current rheumatology reports · 2024Review
- Towards Personalized Medicine in Rheumatoid Arthritis.Open access rheumatology : research and reviews · 2024Review
- Identification of Cell-Specific Differential DNA Methylation Associated With Methotrexate Treatment Response in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- An overview of DNA methylation-derived trait score methods and applications.Genome biology · 2023Review
- 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
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
objectivesIdentifying blood-based biomarkers that predict treatment response in RA is a clinical priority. We investigated differential DNA methylation as a candidate biomarker of response for the first-line drug used in RA, MTX.
methodsDNA methylation was measured in DNA samples from individuals recruited to the Rheumatoid Arthritis Medication Study. Differentially methylated positions were compared between whole blood samples collected at baseline and at 4 weeks from patients who, by 6 months, had a good (n = 34) or poor response (n = 34) to MTX using linear modelling, adjusting for gender, age, cell composition, baseline 28-joint disease activity score (DAS28) and smoking status. Analyses also compared methylation with changes in DAS28 and changes in swollen joint count and tender joint count, and changes in CRP over the initial 6 months after MTX commencement. Differentially methylated positions showing significant differences with any response parameter were tested using pyrosequencing in an independent group of 100 patients from the Rheumatoid Arthritis Medication Study.
resultsIn the discovery group, two CpG sites showed methylation changes at 4 weeks associated with clinical EULAR response by 6 months. Significant changes in methylation for three differentially methylated positions associated with change in tender joint counts, three with change in swollen joint count and a further four with change in CRP. Of the 12 CpGs, four showed replicated association in an independent dataset of samples from the Rheumatoid Arthritis Medication Study.
conclusionThese data represent an advance on current practice by contributing to a personalized medicine strategy allowing an escalation or change in therapy as early as 4 weeks.
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