Certain Genetic Factors Associated With Rheumatoid Arthritis Severity, Risk of Death and Response to Treatment


Genetic variations associated with the risk of susceptibility to rheumatoid arthritis are also associated with responsiveness to treatment, the risk of death, and severity of the disease as measured by imaging, according to a study in the April 28 issue of JAMA.1

Advances have been made in identifying genetic susceptibility loci (the specific site of a particular gene on its chromosome) for autoimmune diseases, but evidence is needed regarding their association with disease prognosis and treatment response, according to background information in the article.

Anne Barton, Ph.D., F.R.C.P., of the University of Manchester, England, and colleagues examined whether specific HLA-DRBl (a gene) haplotypes (a set of DNA or genetic variations) associated with rheumatoid arthritis (RA) susceptibility are also associated with severity (as measured by radiological imaging), death, and response to medications (tumor necrosis factor [TNF] inhibitor drugs). For the analysis, the researchers used data from several sources that totaled 2,112 patients to evaluate radiologic severity; 2,432 patients to assess mortality; and 1,846 patients to examine treatment response to TNF inhibitor therapy. All patients were from the United Kingdom.

The researchers found that the HLA-DRBl locus was associated with radiological severity of RA, risk of death, and response to treatment with TNF inhibitor therapy.

“Replication of these findings in other cohorts is needed as a next step in evaluating the role of HLA-DRBl haplotype analysis for management of RA,” authors write.

The results of this study are important for 3 reasons, write David T. Felson, M.D., M.P.H., of the Boston University School of Medicine, and Lars Klareskog, M.D., Ph.D., of the Karolinska Institutet/Karolinska University Hospital, Stockholm, in an accompanying editorial.2

“First, these findings may add to the ability to predict outcomes of RA, thus helping to optimize therapeutic strategies for different patients. Second, the findings may add to the understanding of the molecular mechanisms that determine disease course and mortality. … Third, the findings by Viatte et al also help to inform understanding of disease pathogenesis by strongly implicating HLA-dependent immune events not only for the onset of RA, but also for disease course and mortality.”

“Although the findings reported by Viatte and colleagues may not have immediate clinical implications, identification of the precise HLA variants that influence disease course is of great interest. These observations open the door to further research, including replication for this haplotype and discovery related to its combination with other determinants of disease development and progression. Such discoveries will prove helpful both to understand and predict the variable disease course and response to therapy that occurs in patients with rheumatoid arthritis.”


1. doi:10.1001/jama.2015.3435;

2. doi:10.1001/jama.2015.1710;