New research suggests DNA methylation profiling could predict rheumatoid arthritis patient’s response to treatment
A new study published in the Arthritis & Rheumatology journal has indicated that DNA methylation profiling, in which changes to the level of DNA methylation are recorded, may provide a method of predicting response to rheumatoid arthritis drug etanercept.
The level of DNA methylation is a reflection of how active a gene is and may provide a method of predicting response to the biologic drugs used to treat rheumatoid arthritis.
Biologic drug therapies, including etanercept, represent a huge advance in the treatment of rheumatoid arthritis; however, very good disease control is only achieved in 30% of patients, making identification of predictors of response a research priority.
Mr Darren Plant from the NIHR Manchester Musculoskeletal Biomedical Research Unit (BRU) hypothesized that differential DNA methylation patterns may provide biomarkers predictive of response to TNF-inhibitor (TNFi) therapy in patients with rheumatoid arthritis.
An epigenome-wide association study was performed on pre-treatment whole blood DNA from patients with rheumatoid arthritis. DNA methylation patterns were compared between patients who displayed good response (n=36) or no response (n=36) to etanercept therapy at 3-months.
The results highlighted the importance of one gene, called LRPAP1 where two DNA methylation markers were increased in the non-responder group, indicating that the gene may be less active in those patients unlikely to respond to etanercept. A genetic sequence change was found to correlate with the level of DNA methylation and, in a separate group of patients treated with anti-TNF biologic drugs, the genetic change also occurred more commonly in patients whose disease activity was less likely to respond to treatment.
Professor Anne Barton from the Arthritis Research UK Centre for Genetics and Genomics at The University of Manchester concluded:
Our results indicate that DNA methylation profiling may provide a new biomarker of response to etanercept in patients with rheumatoid arthritis. Confirmation in a larger, independent group of patients is now needed to confirm this finding, before it can be brought into clinical practice.
“In the future we hope this research may help form clinical guidance on predicting if a patient will respond well to etanercept as a rheumatoid arthritis treatment.”
