DNA Methylation Signatures of Response to Conventional Synthetic and Biologic Disease-Modifying Antirheumatic Drugs (DMARDs) in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is a complex condition that displays heterogeneity in disease severity and response to standard treatments between patients. Failure rates for conventional, target synthetic, and biologic disease-modifying rheumatic drugs (DMARDs) are significant. Although there are models for predicting patient response, they have limited accuracy, require replication/validation, or for samples to be obtained through a synovial biopsy. Thus, currently, there are no prediction methods approved for routine clinical use. Previous research has shown that genetics and environmental factors alone cannot explain the differences in response between patients. Recent studies have demonstrated that deoxyribonucleic acid (DNA) methylation plays an important role in the pathogenesis and disease progression of RA. Importantly, specific DNA methylation profiles associated with response to conventional, target synthetic, and biologic DMARDs have been found in the blood of RA patients and could potentially function as predictive biomarkers. This review will summarize and evaluate the evidence for DNA methylation signatures in treatment response mainly in blood but also learn from the progress made in the diseased tissue in cancer in comparison to RA and autoimmune diseases. We will discuss the benefits and challenges of using DNA methylation signatures as predictive markers and the potential for future progress in this area.

Anti-inflammatory and antiresorptive effects of acyl substitution chromone derivatives in experimental model of rheumatoid arthritis

“…Например, по данным Wang S.S. и соавт. частота терапевтических неудач, как в случае применения классических противоревматических средств, так и современных таргетных препаратов, остается достаточно высокой [19].…”

The efficacy and safety of short-term and low-dose IL-2 combined with tocilizumab to treat rheumatoid arthritis

“…The etiology of RA remains incompletely understood, with genetic, autoimmune, and environmental factors being considered as the primary causes ( 6 ). Individuals with genetic predisposition may experience abnormal immune responses in synovium triggered by environmental factors, resulting in synovitis characterized by joint swelling, pain, and irreversible damage ( 7 ). T lymphocyte subgroups and their released pro-inflammatory or anti-inflammatory cytokines exist widely in synovitis and play an indispensable role in perpetuating the inflammatory response ( 8 , 9 ).…”

Novel DNA methylome biomarkers associated with adalimumab response in rheumatoid arthritis patients

“…Furthermore, differentially methylated patterns have been reported in peripheral mononuclear blood cells, fibroblast-like synoviocytes, and synovial T cells of RA patients (15,20,23). DNA methylation in peripheral blood or methylome has therefore been proposed as a biomarker tool to predict therapy response in RA patients (24). Different studies investigated the association of the DNA methylome with response to methotrexate in RA patients (25)(26)(27)(28)(29)(30)(31).…”