Providing treatment options for patients with rheumatoid arthritis is paramount to treating the disease. Although existing therapies have been effective, treatment response is still a concern in this patient population.
“Biologic drug therapies represent a huge advance in treatment of rheumatoid arthritis,” Darren Plant, PhD, National Institute for Health Research Manchester Musculoskeletal Biomedical Research Unit, Manchester Academy of Health Sciences, United Kingdom, and colleagues explained. “However, very good disease control is achieved in only 30% of patients, making identification of biomarkers of response a research priority.”
Allele Linked to Nonresponse
To determine whether differential DNA methylation patterns are a useful biomarker of tumor necrosis factor inhibitor therapy response, the investigators conducted an epigenome-wide association study to look at differences between good responders and nonresponders treated with etanercept. The data used for this study were based on patients from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate, and included patients aged ≥18 years who were clinically classified with rheumatoid arthritis per the American College of Rheumatology criteria. Thirty-six patients were included in each group, and response at 3 months was the time frame of interest.
Altogether, 5 positions were differently methylated between responders and nonresponders; the top 2 positions mapped to exon 7 of the LRPAP1 gene on chromosome 4. In addition, Dr Plant and colleagues identified a correlation between the A allele of the single-nucleotide polymorphism rs3468 and higher levels of methylation for these 2 positions. That particular allele was also associated with nonresponse, based on criteria from the European League Against Rheumatism.
Treatment Response Multifactorial
These data point to the functional significance of the LRPAP1 gene. The gene itself is highly expressed in mononuclear blood cells, and encodes a protein that influences transforming growth factor β activity. Targeted ribonucleic acid sequencing of specific cell types in whole blood should be considered in future research, the study authors noted.
Although treatment response is multifactorial, Dr Plant and colleagues concluded, biomarker panels that include serology, and epigenetic, genetic, and transcriptomic factors may help better predict treatment response to therapy in patients with rheumatoid arthritis.
- Plant D, Webster A, Nair N, et al. Differential methylation as a biomarker of response to etanercept in patients with rheumatoid arthritis. Arthritis Rheumatol. 2016;68:1353-1360.